Search

In this narrative review, we will explore the different options for salvage re-irradiation for locally recurrent prostate cancer. Brachytherapy (BT) and stereotactic body radiation therapy (SBRT) appear to be successful options. We detailed doses, volumes, oncological outcomes, and toxicity events to identify the best salvage strategy. Salvage reirradiation can only be proposed in certain cases, depending on the patient and the clinical scenario. Specific imaging and tests are needed to safely deliver this treatment. [ABSTRACT FROM AUTHOR]

Objectives • This study aimed to explore the clinical characteristics of patients with prostate cancer with prostate-specific antigen (PSA) concentrations of less than 4 ng/mL (normal PSA) to provide clinical insights regarding diagnosis and treatment. Methods • We recruited 35 patients with prostate cancer with normal PSA who were admitted to Xi’an People’s Hospital from January 2013 to January 2018, and further determined their clinical characteristics, serum PSA concentration, prostate volume, tumor pathology, surgical margins, seminal vesicle invasion, lymph node metastasis, Gleason score, TNM staging, risk classification, and survival, and described the patients’ interventions and treatments. All patients and their families signed informed consent forms before enrollment. Results • In our study, we observed a 3-year survival rate of 77.14% for patients with prostate cancer and normal PSA concentrations. This outcome can be attributed to several clinical characteristics, including the absence of obvious clinical presentation, a high detection rate of seminal vesicle invasion, as well as high Gleason scores and risk levels. The primary outcome, 3-year survival rate, reflects the long-term prognosis of this specific patient subgroup. We also conducted correlation analyses to better understand the relationships between these clinical characteristics and patient survival. [ABSTRACT FROM AUTHOR]

Le cancer de la prostate est le plus fréquent chez l'homme et, au stade localisé, les schémas d'hypofractionnement de la radiothérapie sont devenus des standards, mais l'absence de risque aggravé de toxicité aiguë et tardive génito-urinaire et gastro-intestinale de l'escalade de dose reste à prouver. La population étudiée comprenait tous les patients pris en charge à l'institut Curie de février 2016 à mars 2018 pour un adénocarcinome prostatique localisé traité par irradiation externe délivrée par un accélérateur linéaire en technique conformationnelle avec modulation d'intensité guidée par l'image à la dose totale de 75 Gy en 30 fractions de 2,5 Gy dans le volume cible prévisionnel comprenant la prostate et les vésicules séminales proximales, et pouvait associer une radiothérapie prophylactique ganglionnaire de 46 Gy en 23 fractions avec la technique de boost intégré. En tout, 166 patients ont été inclus, dont 114 étaient atteints de cancer de risque au moins intermédiaire défavorable (soit 68,7 %). L'âge et le suivi médians étaient de 71,4 ans et 3,96 ans. Cent quarante-neuf patients ont reçu une radiothérapie ganglionnaire (soit 89,8 %). Cent trente et un patients ont reçu une hormonothérapie (soit 78,9 %). Une toxicité génito-urinaire de grade 2 ou plus a été notée en cours de radiothérapie, à 6 mois, 1 an et 5 ans respectivement dans 36,7 %, 8,8 %, 3,1 % et 4,7 % des cas. Deux patients ont souffert à 5 ans d'une toxicité de grade 4 (soit 1,6 %). Une toxicité gastro-intestinale de grade 2 ou plus a été notée en cours de radiothérapie, à 6 mois, 1 an et 5 ans dans respectivement 15,1 %, 1,9 %, 14,6 % et 9,3 % des cas. Parmi ces derniers, huit patients ont souffert d'une toxicité de grade 3 (soit 6,2 %). Il n'y a eu aucune toxicité de grade 4. Les analyses n'ont pas mis en évidence de facteur prédictif de toxicité. Les taux de survie globale, sans progression et spécifique à 5 ans étaient respectivement de 82,4 %, 85,7 % et 93,3 %. La concentration sérique d'antigène spécifique de la prostate et les facteurs de risque cardiovasculaires ont été retrouvés comme facteurs prédictifs d'une dégradation de la survie globale (p = 0,0028 pour les deux). La radiothérapie externe pour un cancer prostatique localisé avec notre schéma modérément hypofractionné avec escalade de dose est bien tolérée. En l'absence de toxicité tardive majorée, l'analyse des modes de rechutes à long terme sera intéressante pour déterminer l'intérêt de cette escalade de dose sur les rechutes locales et à distance. Prostate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated. The study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75 Gy in 30 fractions of 2.5 Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46 Gy in 23 fractions with simultaneous integrated boost. A total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4 years and 3.96 years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6 months, 1 year and 5 years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5 years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6 months, 1 year and 5 years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P = 0.0028 for both). External radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses. [ABSTRACT FROM AUTHOR]

Objective • To investigate the diagnostic value of transforming growth factor-β1 (TGF-β1), prostate-specific antigen isomer 2 (p2PSA) combined with a prostatespecific antigen (PSA) in prostate cancer (PCa). Methods • From October 1, 2019 to September 1, 2022 we enrolled a total of 90 patients with PCa90 patients with PCa in the urology department of our hospital were selected as the PCa group, 90 patients with benign prostatic hyperplasia (BPH) were selected as the BPH group, and 90 healthy people were selected as a healthy control group. The levels of TGF-β1, p2PSA and PSA in serum were detected, and the differences in TGF-β1, p2PSA and PSA levels among the three groups and PCa patients with different pathological parameters were compared. Univariate and Logistic regression analyses were used to analyze the independent risk factors affecting the occurrence of PCa. With pathological results as the ‘gold standard’, the diagnostic efficacy of TGF-β1, p2PSA and PSA alone and their combination for PCa was analyzed by the receiver operating characteristic (ROC) curve. Results • The levels of serum PSA, p2PSA, and TGF-β1 in the PCa group were higher than those in the BPH group and control group (P < .001), and those in BPH group were higher than those in the control group (P < .001). The serum indexes of PCa group increased with the increase of Glerson grade and TNM stage (P < .001). The serum indexes of patients with lymph and bone metastasis were significantly higher than those without lymph and bone metastasis (P < .001). Logistic regression analysis showed that PSA, p2PSA and TGF-β1 were independent risk factors for PCa (P < .001). The area under the ROC curve (AUC) of PSA, p2PSA, TGF-β1 and combined detection were 0.738, 0.862, 0.821 and 0.932, respectively. The AUC of combined detection was greater than that of single detection (P < .001). Conclusion • The expression levels of serum TGF-β1, p2PSA and PSA are related to PCa and are independent risk factors for PCa. The combined detection of the three groups can improve the diagnostic efficacy of PCa. Combined testing improves diagnostic accuracy for prostate cancer, allows for early intervention, and improves patient survival and confidence in treatment options. This will significantly improve the clinical management of prostate cancer. Future studies could explore other biomarkers or molecular indicators to further improve the accuracy of diagnosis and grading of prostate cancer. Additionally, differences between different populations and subtypes can be studied to better understand the heterogeneity of prostate cancer. [ABSTRACT FROM AUTHOR]

Sexual concerns after prostate cancer (PCa) treatment are high. Flexible coping is a crucial element to maintaining sexual activity after PCa and improves adaptation outcomes. We aimed to identify potential sexual adaptation styles reported by men following PCa treatment, and to assess relationships among associated variables and outcomes. Individuals (n = 223) with PCa treatment history (e.g., radical prostatectomy [n = 165, 74.0%], external beam radiation [n = 83, 37.2%], hormone/androgen deprivation therapy [n = 83, 37.2%]), completed an online survey assessing sexual variables and processes of sexual adaptation. Using a combination of inductive and deductive coding, open-ended responses were thematically analyzed and grouped into sexual adaptation styles. Factors potentially associated with sexual adaptation styles (e.g., age, perceived partner involvement, co-morbidities, relationship duration, time since PCa treatment, desire for physical affection, depression, relationship adjustment) were tested using multinomial logistic regression. Outcomes of sexual well-being (sexual distress, sexual bother, sexual satisfaction) and relationship adjustment were compared against each sexual adaptation style using a multivariate analysis of variance. Sexual activity status and satisfaction with the adaptation process was assessed across the sexual adaptation styles using a chi-square analysis and post-hoc tests. Two distinct categories were identified: those who had Adapted (n = 185) and those who had Not Adapted (n = 38). Four sexual adaptation styles emerged in the adapted category: Relationship Renegotiation (n = 53) and Sexual Renegotiation (n = 47), which were couples-focused styles, and Acceptance/Resignation (n = 34) and Masturbation/Erection (n = 48), which were individual-focused styles. Participants who could not be categorized as one style, but rather met several, were identified as Mixed (n = 3). Higher rates of depression, lower relationship adjustment, lack of sexual activity, and greater dissatisfaction with the adaptation process were observed for Not Adapted participants. Participants engaged in any type of adaptation style fared better than those who had Not Adapted. Couples-focused styles tended to emphasize renegotiation, including a changed perspective on the expression of the relationship. Perceived direct engagement of the partner facilitated adaptation and emphasized engagement with flexible coping, either through redefining priorities or ways of being sexual. Individual-focused styles emphasized pre-cancer erectile function, and either aimed to return to capacity for penetrative sexual activity or accepted its inaccessibility and largely an abandonment of partnered sexual activity. [ABSTRACT FROM AUTHOR]

The evolution of radiation therapy techniques goes hand in hand with the evolution of the profession of radiation therapist. In the particular context of online adaptive radiotherapy based on cone beam computed tomography images, delegation of certain tasks from the physician to the radiation therapist is possible within the framework of a cooperation protocol. This delegation requires prior theoretical and practical training. It enriches the practice of radiation therapists by allowing them to acquire new skills and greater autonomy. It foreshadows access for radiation therapists to advanced practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer presents significant challenges due to its high incidence and prevalence, as it is the most common non-skin cancer in men. The timely detection of prostate cancer and its metastasis is crucial for patient outcomes. Prostate-specific membrane antigen (PSMA) emerges as a promising biomarker for its early detection, due to its specificity and membrane localization on tumor cells. Utilizing PSMA-targeting particles in conjunction with positron emission tomography (PET) scans enhances the accuracy of tumor detection compared to PET alone. This advancement has led to innovative treatment modalities such as Prostate-specific membrane antigen-targeted radionuclide therapies (PSMA-TRTs), which have shown promise in reducing or eliminating tumors, as evidenced by declines in prostate-specific antigen (PSA) levels post treatment. However, PSMA-TRT carries both benefits and adverse effects, with the long-term ones as yet unknown. The short-term adverse effects include fatigue, nausea, pain flares, and potential radiation exposure to others. Further research is needed to explore PSMA-TRT's long-term efficacy and potential applications beyond prostate cancer. Prostate cancer is one of the most challenging malignancies due to its high incidence and prevalence, as it is the most frequently diagnosed non-skin cancer in men. The timely identification of prostate cancer and its metastasis is paramount for ensuring favorable outcomes for patients. Prostate-specific membrane antigen (PSMA) emerges as a promising biomarker for its detection, due to its specificity. This makes it an ideal target for the early identification of a metastatic phenotype. Situated on the membrane of tumor cells, PSMA facilitates the attachment of PSMA-targeting particles, enabling their detection through positron emission tomography (PET) scans with relative ease. Utilizing these imaging agents in conjunction with PET scans enhances the accuracy of prostate cancer tumor detection compared to PET scans alone. The advancement in prostate cancer imaging has paved the way for innovative treatment modalities. Prostate-specific membrane antigen-targeted radionuclide therapies (PSMA-TRT) exploit PSMA imaging agents to target identified prostate cancer malignancies with precise radiation, thereby reducing or eliminating the tumor mass. PSMA-TRT exhibits significant promise in prostate cancer therapy, evident from the notable declines in prostate-specific antigen (PSA) levels post treatment. However, PSMA-TRT carries both beneficial and adverse effects. While it represents a substantial leap forward in tumor cell imaging, PSMA-based antigens, being larger particles than ligands, offer prolonged imaging capabilities. Yet, the long-term effects of PSMA-TRT remain unknown, with the short-term adverse ones including fatigue, nausea, pain flares, and potential radiation exposure to others. [ABSTRACT FROM AUTHOR]

Erectile function preservation is an important quality of life factor in patients treated for prostate cancer. A dose-optimization approach on sexual structures was developed and evaluated to limit erectile dysfunction after radiotherapy. Twenty-three men with localized prostate cancer and no erectile dysfunction were enrolled in the study. All patients received a prescription dose between 76 and 78 Gy. Computed tomography/magnetic resonance image registration was used to delineate the prostatic volume and the sexual structures: internal pudendal arteries (IPA), penile bulb and corpus cavernosum. Erectile function was evaluated using the 5-items International Index of Erectile Function (IIEF-5) score every 6 months during the 2 years after radiotherapy and once a year afterwards. No erectile dysfunction, mild erectile dysfunction and severe erectile dysfunction were defined if the IIEF-5 scores were 20–25, 17–19 and < 17, respectively. The mean follow-up was 4.5 years. The mean age of the patients was 66.3 years. At 2 years, 67% of the patients had no erectile dysfunction, 11% had mild erectile dysfunction and 22% had severe erectile dysfunction. No significant difference was found between the patients with and without erectile dysfunction (IIEF-5 ≥ 20 and IIEF-5 < 20, respectively) for any of the parameters: dosimetric values (internal pudendal arteries, penile bulb, corpus cavernosum), age, comorbidity and smoking status. The biochemical-relapse free survival was 100% at 2 years. This approach with dose-optimization on sexual structures for localized prostate cancer found excellent results on erectile function preservation after radiotherapy, with 78% of the patients with no or mild erectile dysfunction at 2 years. [ABSTRACT FROM AUTHOR]

We investigated the association between pre-existing comorbidities and prostate cancer management. High overall comorbidity burden, cardiac and respiratory disorders, thrombosis, diabetes, depression and anxiety, and chronic pain were associated with selecting EBRT, ADT alone or watchful waiting over RP. Introduction: We aimed to assess the association between comorbidities and prostate cancer management. Patients and methods: We studied 12,603 South Australian men diagnosed with prostate cancer between 2003 and 2019. Comorbidity was measured one year prior to prostate cancer diagnosis using a medication-based comorbidity index (Rx-Risk). Binomial logistic regression analyses were used to assess the association between comorbidities and primary treatment selection (active surveillance, radical prostatectomy (RP), external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT), brachytherapy, ADT alone, and watchful waiting (WW)). Certain common comorbidities within Rx-Risk (cardiac disorders, diabetes, chronic airway diseases, depression and anxiety, thrombosis, and chronic pain) were also assessed. All models were adjusted for sociodemographic and tumor characteristics. Results: Likelihood of receiving RP was lower among men with Rx-Risk score ≥3 (odds ratio (OR) 0.62, 95%CI:0.56-0.69) and Rx-Risk 2 (OR 0.80, 95%CI:0.70-0.92) compared with no comorbidity (Rx-Risk ≤0). Men with high comorbidity (Rx-Risk ≥3) were more likely to have received ADT alone (OR 1.76, 95%CI:1.40-2.21), EBRT (OR 1.30, 95%CI:1.17-1.45) or WW (OR 1.49, 95%CI:1.19-1.88) compared with Rx-Risk ≤0. Pre-existing cardiac and respiratory disorders, thrombosis, diabetes, depression and anxiety, and chronic pain were associated with lower likelihood of selecting RP and higher likelihood of EBRT (except chronic airway disease) or WW (except diabetes and depression and anxiety). Cardiac disorders and thrombosis were associated with higher likelihood of selecting ADT alone. Furthermore, age had greater effect on treatment choice than the level of comorbidit y. Conclusion: High comorbidit y burden was associated with primary treatment choice, with significantly less RP and more EBRT, WW and ADT alone among men with higher levels of comorbidity. Each of the individual comorbid conditions also influenced treatment selection. [ABSTRACT FROM AUTHOR]

A study of 3425 men showed that those with STAR-CAP stages 1A-1C had similar risk of needing additional therapies and developing metastases after primary treatment. Stages 2A to 3B increased the risk of these outcomes. Men who underwent surgery were more likely to receive subsequent therapy, while radiation therapy patients were more likely to receive upfront intensified multimodality therapies. Introduction: The International Staging Collaboration for Prostate Cancer (STAR-CAP) has been proposed as a risk model for prostate cancer with superior prognostic power compared to the current staging system. This study aimed to evaluate the performance of STAR-CAP in predicting the risk of subsequent therapy after initial treatment and the risk of developing metastases. Patients and Methods: The study included 3425 men from an institutional observational registry with a median age of 64.9 years and a median follow-up time of 5.4 years. The primary endpoints were metastases and progression to additional therapy after initial therapy (radiation ± surgery). The risk of progression in the STAR-CAP group was estimated using a competing risk model (death). Results: The results showed that patients with STAR-CAP stages 1A-1C had a similar risk of requiring additional therapies and developing metastasis. Compared to stage IC, each stage from 2A to 3B incrementally increased the risk of subsequent therapy (hazard ratio (HR) 1.4-5.8, respectively) and metastases (HR 1.5-10.8, respectively). The 5-year probability of receiving subsequent therapy for a patient with stage IC was 8.6%, which increased from 11.4% to 37.4% for those with stages 2A to 3B. The 5-year probability of developing metastases for patients with stage IC was 1.5%, which increased from 2.2% to 8.2% for patients with stages 2A to 3B. Conclusions: The probability of receiving subsequent therapy was higher for patients undergoing surgery, while radiation therapy patients were more likely to receive treatment with intensified multimodality therapies upfront. [ABSTRACT FROM AUTHOR]

PSMA-directed radioligand therapies can cause dry mouth; however, there are no studies to date focusing exclusively on the oral toxicities of PSMA-targeted immunotherapies. We found that the adverse effects of PSMA-targeted immunotherapies included dry mouth, dysgeusia, and mucositis. We advocate for the oncology community to be aware of potential oral toxicities and to consider involving oral medicine specialists in patient care. Introduction: Prostate Specific Membrane Antigen (PSMA)-targeted radionucleotide therapy has been shown to cause dry mouth, but the oral manifestations of PSMA-targeted immunotherapy have not been extensively studied. The aim of this study was to describe and quantify the oral manifestations of PSMA-targeted immunotherapies (bispecific antibodies or Chimeric Antigen Receptor T cell therapies) in the management of metastatic castration resistant prostate cancer. Patients and Methods: We performed a retrospective analysis of the oral toxicities of PSMA-targeted immunotherapies of the patients seen at a single institution's cancer center between 2020 and 2023. Descriptive statistics were used to summarize the data. Results: In a total of 19 patients treated with PSMA-targeted immunotherapies between 2020 and 2023, 9 patients (47%) experienced the following oral toxicities: xerostomia (n = 6; 32%), mucositis (n = 2; 10%), dysgeusia, dry throat and teeth sensitivity in (n = 1 each; 5%), respectively. Oral infections, such as candidiasis and herpes simplex, were not observed in any patients. Mucositis was managed with salt rinses and resolved within few months from onset. Xerostomia persisted in all the patients (median: 306 days, range: 98-484 days) among those who reported dry mouth at the time of data collection, despite treatment with salivary stimulants (n = 5; 83%). Dysgeusia was also persistent, although it was not specifically treated. Conclusions: Patients treated with PSMA-targeted immunotherapies for prostate cancer can present with various short-term and long-term off-tumor on-target oral toxicities including xerostomia and dysgeusia that may affect quality of life. This study serves as a foundation to future prospective studies with a larger sample size and also helps oncologists managing prostate cancer patients with targeted immunotherapies to familiarize common oral toxicities. Furthermore, we emphasize the importance of oral medicine consultation for a comprehensive oral examination and management of oral complications. [ABSTRACT FROM AUTHOR]

Metastatic hormone-sensitive prostate cancer benefits from upfront treatment intensification. To date, we do not have a validated prognostic model to guide treatment choice. In our study, docetaxel-treated patients with high Gleason score, high disease burden, pain or unfavorable laboratory parameters at baseline had worse outcomes. These results may be useful in tailoring treatment in this setting. Background: Treatment of metastatic hormone-sensitive prostate cancer (mHSPC) dramatically changed. PEACE-1 and ARASENS trials established triplet therapy efficacy. Identifying prognostic factors supporting treatment choice is pivotal. Methods: TEAM is an observational, retrospective study to evaluate prognostic role of variables in mHSPC patients receiving upfront docetaxel in 11 Italian centers. Outcome measures were progression-free survival (PFS) and overall-survival (OS). Results: From September 2014 to December 2020, 147 patients were included. Median PFS and OS were 11.6 and 37.4 months. At univariate analysis, PFS-related variables were Gleason Score (GS) (P = .001), opioid use (P = .004), bone metastases number (P < .001), baseline PSA (P = .006), Hb (P < .001), ALP (P < .001) and LDH (P = .002), time between ADT and docetaxel start (P = .018), 3-month PSA (P < .001) and ALP (P < .001), and number of docetaxel cycles (P < .001). OS-related variables were PSA at diagnosis (P = .024), primary tumor treatment (P = .022), baseline pain (P = .015), opioid use (P < .001), bone metastases number (P <. 001), baseline Hb (P < .001), ALP (P < .001) and LDH (P = .001), NLR ratio (P = .039), 3-month PSA (P < .001) and ALP (P < .001) and docetaxel cycles number (P < .001). At multivariate analysis, independent prognostic variables were GS, opioid use, baseline LDH and time between ADT and docetaxel initiation for PFS, and baseline Hb and LDH for OS. Conclusion: Patients receiving upfront docetaxel with high GS, high disease burden, pain or opioid use, baseline unfavorable laboratory values had worse outcomes. Patients had greater docetaxel benefit when initiated early after ADT start. These parameters could be taken into account when selecting candidates for triplet therapy. [ABSTRACT FROM AUTHOR]

The risk of CRPC-M1 did not significantly vary according to the type of ADT used at progression. The risk of a CRPC-M0 progression increased 3.48 times using continuous ADT when compared to IAD. Introduction: To analyze whether the use of an intermittent (IAD) versus continuous (CAD) androgen deprivation therapy for the treatment of biochemical progression after primary treatments in prostate cancer can influence the development of nonmetastatic castration resistant prostate cancer (CRPC-M0). Patients: 170 male patients with an histologically confirmed diagnosis of PC, presenting a biochemical progression after primary treatments (82 after radical prostatectomy and 88 after external radiation therapy), nonmetastatic at imaging were considered for continuous (85 cases) or intermittent (85 cases) administration of androgen deprivation therapy. Methods: we retrospectively collect all data regarding histological diagnosis, primary treatment, imaging for M0-M1 staging, PSA at progression, time to biochemical progression from primary therapy, ADT used, IAD cycles, so to compare in 2 groups (IAD vs. CAD) time for progression from the beginning of ADT treatment and type of progression in terms of CRPC-M0 versus CRPC-M1 cases. Results: no significant (P = .4955) difference in the whole CRPC progression was found between IAD (25.8%) and CAD (30.5%) treatment at a mean of 32.7 ± 7.02 months and 35.6 ± 13.1 months respectively (P = .0738). Mean PSA at CRPC development was significantly higher in the IAD group (5.16 ± 0.68 ng/mL) than in the CAD group (3.1 ± 0.7 ng/mL) (P < .001). In all cases, imaging to detect M status at CRPC development was PET TC scan. At univariate analysis CAD administration significantly increases the RR for CRPC-M0 progression (RR 3.48; 95%CI 1.66-7.29; P = .01) when compared to the IAD administration, and this effect at multivariate analysis remained significant and independent to the other variables (RR 2.34, 95%CI 1.52-5.33; P = .03). Conclusions: in our population with biochemical progression after primary treatment for PC, the intermittent administration of ADT significantly reduces the risk to develop CRPC-M0 disease when compared to a continuous administration of ADT, whereas no difference between the 2 strategies in terms of CRPC-M1 progression exists. [ABSTRACT FROM AUTHOR]

We assessed national trends in management of newly diagnosed prostate cancer across risk groups of noncancer mortality. We found use of treatment has been increasing among men with very-high risk of noncancer mortality within 10 years. It will be important for further work to assess the appropriateness of these trends in the context of existing evidence. Background: Deciding whether to treat or conservatively manage patients with prostate cancer is challenging. Recent changes in guidelines, advances in treatment technologies, and policy can influence decision making surrounding management, particularly for those for whom the decision to treat is discretionar y. Contemporar y trends in management of newly diagnosed prostate cancer are unclear. Methods: Using national Medicare data, men with newly diagnosed prostate cancer were identified between 2014 and 2019. Patients were classified by 5- and 10-year noncancer mortality risk. Multinomial logistic regression models were fit to assess adjusted trends in management over time. The primary outcome was management of prostate cancer: local treatment (inclusive of surgery, radiation, brachytherapy, or cryotherapy), hormone therapy, or observation. Results: Local treatment was the most common form of management and stable across years (68%). Use of observation increased (21%-23%, P < .001) and use of hormone therapy decreased (11%- 8%, P < 0.001). After stratifying by 10-year non-cancer mortality risk, observation increased among men with low (22.3%-26.1%, P < .001) and moderate (19.9%-23.5%, P < .001) mortality risk. Conversely, use of treatment increased among those with high (62.8%-68.0%, P = .004) and very high (45.5%-54.1%, P < .001) risk of noncancer mortality. These trends were similar across groups when stratified by 5-year noncancer mortality risk. Conclusion: Nationally, use of local treatment remains common and was stable throughout the study period. However, while local treatment declined among men with a lower risk of noncancer mortality, it increased among men with a higher risk of non-cancer mortality. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer has become one of the leading causes of death in men. Cancer patients often seek alternative treatments apart from chemotherapy, radiation therapy, and surgery. The use of medicinal plants in both preventive and curative actions in healthcare has been widely recognized. One of the plants known to have anticancer activity is the soursop leaf (Annona muricata L.). Objective: This study was conducted to explore the potential of active compounds contained in A. muricata as drug candidates for the inhibition of caspase-3 in silico. Methods: The research began with the prediction of Lipinski's Rule of Five and ADMET properties for the compounds found in A. muricata. The prediction process was followed by pharmacophore modelling and molecular docking simulations on caspase-3 (PDB: 1NME) as the target protein and 2-hydroxy-5-(2-mercaptoethylsulfamoyl)- benzoic acid as the natural ligand using AutoDockTools 1.5.6. Results: Based on the molecular docking results, 22 test ligands were able to form bonds with the caspase-3 enzyme. The two best interactions were observed with the test ligands, Isolaureline and S-norcorydine, with binding energy values of -6.20 kcal/mol and -6.12 kcal/mol and inhibition constant values of 28.65 µM and 32.53 µM. In terms of receptor-target interactions, these two compounds also exhibited hydrogen bonding and van der Waals interactions similar to the natural ligand. Conclusion: The best bioactive compounds in A. muricata (Isolaureline and S-norcorydine) were predicted to have the ability to interact with caspase-3 and the potential to be used as prostate cancer drug candidates. [ABSTRACT FROM AUTHOR]

Simple Summary: LET-optimized pencil beam scanning (PBS) proton treatment plans have the potential to improve patient outcomes. Dose-escalated x-ray conformal therapy has improved the prostate cancer 5-year freedom from biochemical progression (FFBP) but has also increased gastrointestinal and genitourinary toxicities; toxicities can be reduced by escalating dose via a simultaneously-integrated boost (SIB) to the intraprostatic tumor (IPT). These techniques can be applied with greater precision using protons, which have shown high overall 5-year FFBP and low toxicities, although improvement in FFBP is needed for high-risk patients. Relative biological effectiveness (RBE) of 1.1 is uniformly assumed for proton treatment planning, although an increasing number of studies show that RBE increases with linear energy transfer (LETd). We show improvement with PBS LET-optimized plans over single-field optimized (SFO), or IPT-SIB plans through increased target volume LETd, RBE, and target-to-organs-at-risk (OAR) dose ratios (TODRs). This study also highlights the necessity of developing disease-specific LET-dependent RBE models. Purpose: To demonstrate the feasibility of improving prostate cancer patient outcomes with PBS proton LETd optimization. Methods: SFO, IPT-SIB, and LET-optimized plans were created for 12 patients, and generalized-tissue and disease-specific LET-dependent RBE models were applied. The mean LETd in several structures was determined and used to calculate mean RBEs. LETd- and dose–volume histograms (LVHs/DVHs) are shown. TODRs were defined based on clinical dose goals and compared between plans. The impact of robust perturbations on LETd, TODRs, and DVH spread was evaluated. Results: LETd optimization achieved statistically significant increased target volume LETd of ~4 keV/µm compared to SFO and IPT-SIB LETd of ~2 keV/µm while mitigating OAR LETd increases. A disease-specific RBE model predicted target volume RBEs > 1.5 for LET-optimized plans, up to 18% higher than for SFO plans. LET-optimized target LVHs/DVHs showed a large increase not present in OARs. All RBE models showed a statistically significant increase in TODRs from SFO to IPT-SIB to LET-optimized plans. RBE = 1.1 does not accurately represent TODRs when using LETd optimization. Robust evaluations demonstrated a trade-off between increased mean target LETd and decreased DVH spread. Conclusion: The demonstration of improved TODRs provided via LETd optimization shows potential for improved patient outcomes. [ABSTRACT FROM AUTHOR]

We profiled the genomes of over 12,0 0 0 advanced prostate cancer samples and probed a large clinicogenomic database with ~10 0 0 patients to clarify the impact MYCamp in PCa. Results suggest that MYCamp advanced PCa has limited targeted therapies and is an aggressive subset of advanced prostate cancer found disproportionately more common in men with African ancestry. Background: MYC is a commonly amplified, potentially targetable gene in prostate cancer (PCa). We sought to define the molecular, immunologic, and clinicodemographic landscape of MYC amplification (MYCamp) in advanced PCa to establish a rationale for personalized treatment combinations. Methods: Hybrid capture-based comprehensive genomic profiling (CGP) was performed on PCa tumor samples. MYCamp = copy number =6 (CN). Patients treated between January 2011 and December 2020 were selected from a nationwide deidentified (280 clinics) EHR-derived clinicogenomic database (CGDB). Results: Of 12,528 hormone-sensitive and castrate-resistant (CRPC) samples, MYCamp was detected in 10.6% (median CN = 8). MYCamp was more frequent in men with African versus European ancestry (12.9% vs. 10.2% P = .002), in metastatic vs. primary tissue (15.7% vs. 6.2% P < .001), and enriched in metastatic liver lesions (20.2%), but inversely associated with high microsatellite-instability (0.8% vs. 2.4%, P < .001). MYC CN =15 was associated with PD-L1 expression (26.1% vs. 9.8%, P = .025). Amplification of AR, RAD21,LYN, CCND1,ZNF703,FGF3/4/19, and FGFR1 was enriched in MYCamp vs. MYCwt (all P < .001). In liquid samples with tumor fraction [TF] > 0, MYCamp was detected in 2.0% (28/1,402), and 4.5% (20/445) with TF > 20%. In the CGDB, (67 MYCamp and 658 MYCwt), patients received similar treatments; most received hormone therapies (35.8% MYCamp vs. 31.5% MYCwt) or chemotherapy (37.3% MYCamp vs. 27.7% MYCwt) as first therapy after CGP report. Conclusion: MYCamp defines a biologically distinct subset of PCa patients and is characterized with multiple proxies of advanced disease. These data suggest that MYCamp may be prognostic; independent cohorts are needed to validate these findings. [ABSTRACT FROM AUTHOR]

With more than 1.4 million newly diagnosed cases is the surgical treatment for prostate cancer an important therapy option, regardless of the prostate size. We retrospectively reviewed the records of 909 patients and found that surgery is feasible for very large prostates. Interestingly, these patients had lower positive margin rates. Background: Even the most experienced surgeons experience technical difficulties and challenges when operating on very large prostates, regardless of surgical technique. Our goal was to determine whether preoperative prostate volume has an impact on functional and oncological outcomes after open radical prostatectomy. Materials and Methods: We reviewed the records of 909 patients who underwent open radical prostatectomy by a single surgeon at our institution. Variables were compared across quartile distributions of prostate volume as defined by preoperative transrectal ultrasound examination, including group A with prostate volume < 30ccm 3, group B with prostate volume = 30ccm 3 and < 50ccm 3, group C with prostate volume = 50ccm 3 and < 70ccm 3 and group D with prostate volume = 70ccm3. Factors assessed in this analysis were patient age, preoperative prostate specific antigen (p-PSA), Gleason score, pathological stage, margin status, operative time, cystography leakage, early continence, biochemical recurrence (BCR)-free, and overall-survival (OS). The complication rates were classified using Clavien Dindo classification. Results: There were no statistically relevant differences between the groups considering preoperative factors such as age, p-PSA, Gleason score, and tumor stadium. Patients with a very large prostate had slightly higher percentage of anastomosis leakage, severe Clavien Dindo complication rates (= 3), longer operation time and severe early incontinence (IV °) rates, simultaneously having lower positive margin rates. Nevertheless, the early continence rates, BCR-free and OS were similar regardless of the prostate size. Conclusions: open radical prostatectomy for patients with very large prostate is a viable therapy option with slightly higher ur inary leakage-, ear ly incontinence- and complication-rates that takes slightly more operation time. However, the functional and oncological outcomes are similar when compared to smaller prostates. [ABSTRACT FROM AUTHOR]

Cribriform Gleason pattern 4 and intraductal carcinoma of the prostate are adverse pathologic features. We retrospectively assessed their impact when added to CAPRA and NCCN pretreatment tools in 3 patient cohorts (Toronto, Wisconsin and Rotterdam) and show improved patient stratification for both biochemical recurrence and development of metastases and death of disease (events) with their inclusion. Background: Pretreatment stratification tools can help in clinical decision making in prostate cancer. To date, none incorporates well-established routinely reported adverse prognostic pathologic features such as intraductal carcinoma of prostate (IDC) or cr ibr ifor m patter n 4 (CC). Objective: To assess the impact of addition of CC and/or IDC on the Cancer of Prostate Risk Assessment (CAPRA) and National Cancer Comprehensive Network (NCCN) tools for predicting biochemical recurrence free survival (BCR-FS) and event-free survival (EFS) across multiple patient cohorts. Design, setting, and participants: Matched prostate biopsies and radical prostatectomies from institutions in Toronto, Wisconsin and Rotterdam. The presence/absence of CC/IDC was recorded on all biopsies. Outcome measurements and statistical analysis: Relationship to outcome was assessed using Cox proportional hazard models, ANOVA and Harrell's concordance index. Results and limitations: We included 1326 patients (Toronto-612, Wisconsin-542, Rotterdam-172) with median follow up of 4.2 years (IQR 2.9-6.4 years); 306 (23.1%) had CC/IDC on biopsy with 207 (20.9%) BCR and 154 (11.6%) events (metastases/death). Addition of CC/IDC improved stratification in CAPRA scores 3 to 5 for BCR-FS (c-index increase 0.633-0.658, P < .001) and scores 6-10 for EFS (c-index increase 0.653-0.697, P < .001). For NCCN, all risk groups apart from score 1 to 2 showed improvement in BCR-FS (c-index increase 0.599-0.636, P < 0.001) and EFS prediction (c-index increase 0.648-0.697, P < .001). Sub-analysis of grade group (GG) 2 biopsies showed similar findings. The retrospective nature and inclusion of cases only reported by genitourinary pathologists are study limitations. Conclusions: The clinical benefit of the addition of CC/IDC to both CAPRA and NCCN pretreatment tools was validated in 3 cohorts, including the subset of biopsy GG2 prostate cancer patients. Patient summary: Including additional pathologic features to existing pretreatment, clinical decision making tools improves the ability to predict prostate cancer recurrence, cancer spread and death of disease. [ABSTRACT FROM AUTHOR]

The APC I1307K germline variant confers an increased risk of several malignancies. Here, we report a higher than expected prevalence of treatment-emergent neuroendocrine transformation among men with prostate cancer and germline APC I1307K when compared to a control cohort. If validated, this finding could represent a new biomarker for this aggressive prostate cancer subtype. Introduction: Somatic mutations in the Wnt signaling gene Adenomatous Polyposis Coli (APC) promote metastatic prostate cancer (PCa) progression. Less is known regarding the impact of germline APC mutations on PCa outcomes. We sought to investigate the prevalence of aggressive variant PCa (AVPC) and treatment-emergent neuroendocrine PCa (t-NEPC) in patients with the germline APC I1307K variant, an alteration found in 7% of Ashkenazi Jewish men. Materials and Methods: We report a retrospective cohort study comparing patients with PCa and either APC I1307K germline mutation, APC somatic mutations, or unselected patients. Proportions of patients with AVPC among all the cases were estimated along with 95% Clopper-Pearson exact confidence intervals (CI). Odds ratios with 95% CI were provided for the prevalence of t-NEPC and AVPC in patients with germline APC I1307K compared to patients with frameshift alterations in APC. Results: From 2016-2022, 18 patients with PCa at 3 institutions with the germline APC (I1307K) mutation were identified. Clinically-defined AVPC was found in 8 of the 15 cases with metastatic disease (53%; 95% CI: 26%-79%). Combined somatic alterations in two or more of RB1, TP53 or PTEN (molecularly-defined AVPC) were found in 5/18 cases (28%; 95% CI: 10%-54%). When compared to 20 patients with APC somatic frameshift mutations, patients with the germline APC I1307K variant had a significantly increased risk of AVPC (OR 7.2; 95% CI 1.27, 40.68). Conclusion: PCa that develops in the presence of the germline APC I1307K mutation appear to be enriched for clinically-defined and molecularly-defined AVPC and in particular, for t-NEPC. [ABSTRACT FROM AUTHOR]

For patients with metastatic hormone-sensitive prostate cancer, no head-to-head randomized trial has compared abiraterone and docetaxel when added to androgen deprivation therapy. This real-world efficacy and toxicity analysis of 574 Asian patients demonstrated significantly longer progression-free survival and similar overall survival in those who received the abiraterone over docetaxel combination. Prediction models suggested several prognostic markers, including a ≥ 90% decline in prostate-specific antigen (PSA) level at 3 months, which may be useful for treatment intensification. Introduction: Abiraterone acetate (ABI) or docetaxel (DOC), in addition to androgen-deprivation therapy (ADT), are current treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). No randomized head-to-head trial has compared these 2 mHSPC treatments, and real-world data regarding their outcomes in Asian patients are lacking. Patients and Methods: The medical records of mHSPC patients who began upfront ABI or DOC treatment in addition to ADT at seven public oncology centers in Hong Kong between 2015 and 2021 were reviewed. The primary endpoint was progression-free sur vival (PFS). Secondar y endpoints included overall sur vival (OS), prostate-specific antigen (PSA) response, and toxicities. Kaplan-Meier and multivariate Cox regression analyses were performed. Results: A total of 574 patients were included, of whom 419 received DOC and 155 received ABI. The median follow-up duration was 22.4 (DOC group: 23.8; ABI group: 17.3) months. The ABI group demonstrated significantly better PFS than the DOC group (not reached vs. 15.1 months: hazard ratio = 0.37; 95% confidence interval = 0.28-0.50; P < .001). No significant OS difference was observed (P = .58). Failure to achieve a = 90% decline in PSA level at 3 months and failure to achieve an undetectable PSA nadir were each associated with unfavorable PFS and OS. Patients who received DOC had a higher rate of febrile neutropenia, whereas those who received ABI had higher rates of grade = 3 hypokalemia and elevated alanine transaminase. Treatment discontinuation due to toxicities was more common in the DOC (3.6%) than the ABI (0.6%) group. Conclusion: In Asian mHSPC patients, upfront ABI + ADT was associated with better PFS than 1 DOC + ADT, with no significant OS difference. PSA kinetics may help stratify the prognosis for treatment intensification. Toxicity profiles were different, with a higher rate of toxicity-related treatment discontinuation in the DOC group. [ABSTRACT FROM AUTHOR]

This article explores the impact of androgen deprivation therapy (ADT) on the quality of life, physical activity, anxiety, and depression levels of patients with intermediate- and high-risk prostate cancer. The study involved 78 patients and assessed their well-being, physical activity, and mental health using various questionnaires. The duration of ADT did not significantly affect these factors. However, the study did find a negative correlation between body mass index (BMI) and moderate physical activity, as well as a positive correlation between moderate physical activity and the functional aspect of the quality of life questionnaire. The study concludes that both short-term and long-term use of ADT result in similar side effects, and the risk level of the patients does not significantly impact these side effects. The study suggests that patient education and follow-up may play a role in improving physical activity and quality of life in prostate cancer patients. The study was conducted with ethical approval and informed consent from the participants. [Extracted from the article]

Background: Long-term treatment and associated side effects can affect a patient’s quality of life, one of which is the patient’s regret during the treatment program of prostate cancer. The decision aid (DA) program can help patients with chronic diseases to face disease treatment, but the effect on the treatment of prostate cancer patients has not been evaluated further. This study aims to assess the effect of a decision aid program on treatment regret in prostate cancer patients. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines with the search engines PubMed and Google Scholar from January–March 2023. The inclusion criteria used were randomized controlled-trial studies with full text in English, published for the last ten years, the decision regret during or after the treatment program was reported and the type of regret measurement was described. Results: Based on a literature search, 5 studies met the inclusion criteria. The relationship between decision aid and regret was not significantly lower but had a significant effect in the long-term (12 months) and minority ethnic. Studies on a wider and heterogeneous population are needed to assess the effect of decision aids on the perspective of patients with prostate cancer programs. Conclusions: Decision aid may affect the level of regret of prostate cancer patients in the treatment program. [ABSTRACT FROM AUTHOR]

Prostate cancer is a common malignant tumor in men and early diagnosis and treatment are crucial for the survival rate of patients. This study aimed to establish a machine learning-based prostate cancer prediction model to help physicians accurately identify high-risk patients. This study performed a retrospective analysis using prostate cancer patient data from the MIMIC-IV database. First, the data was cleaned and preprocessed, including imputing missing values, handling outliers, and feature selection. Then, prediction models were established using machine learning algorithms (including logistic regression, support vector machine, deep neural networks, XGBoost, LightGBM and CatBoost) and evaluated using cross-validation and ROC curve analysis. We screened out 1975 patients diagnosed with PC and 11,745 patients diagnosed with BPH based on ICD codes. However, among the BPH patients, 467 were also diagnosed with PC, so we excluded these patients. The LightGBM machine learning model outperformed the other models in distinguishing patients with PC [LightGBM vs. CatBoost vs. XGBoost vs. DNN vs. SVM vs. LR; area under the curve (AUC): 0.93 vs. 0.91 vs. 0.89 vs. 0.86 vs. 0.70 vs. 0.68, respectively]. The LightGBM model had a sensitivity of 86%, specificity of 85% at the best cut-off value. The model was capable of predicting whether a patient has prostate cancer based on their clinical features (including age, Laboratory test, etc.) and had a high level of accuracy and stability. The machine learning-based prostate cancer prediction model established in this study has some clinical application value and can help physicians accurately identify high-risk patients, providing more precise prevention and treatment plans for patients. [ABSTRACT FROM AUTHOR]

In this report we looked at survival outcomes in men with localized prostate cancer and high baseline prostate specific antigen values. At a long follow-up we found that a significant proportion never experience cancer relapse when they received treatment with curative intent. Introduction: Serum prostate specific antigen (PSA) is a well-known prognostic parameter in men with prostate cancer. The treatment of men with very high PSA values and apparently no detectable metastases is not fully established. Patients and Methods: Ancillary analysis from the GETUG 12 phase 3 trial. Patients with non-metastatic high-risk prostate cancer by bone and computerized tomography (CT) scan were randomly assigned to receive androgen deprivation therapy (ADT) and docetaxel plus estramustine or ADT alone. Relapse-free survival (RFS), clinical RFS, metastases-free survival (MFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated using the Kaplan-Meier method for different levels of PSA (50 ng/mL, 75 ng/mL, and 100 ng/mL). The relationship between PSA and outcomes was studied using residual-based approaches and spline functions. Results: The median follow-up was 12 years (range: 0-15.3). Baseline PSA (< 50 ng/mL, n = 328; =50ng/mL, n = 85) was associated with improved RFS (P = .0005), cRFS (P = .0024), and MFS (P = .0068). The 12-year RFS rate was 46.33% (CI 40.59-51.86), 33.59% (CI 22.55-44.97), and 11.76% (1.96-31.20) in men with PSA values < 50 ng/mL (n = 328), 50-100 ng/mL (n = 68), and =100 ng/mL (n = 17), respectively. Exploratory analyses revealed no deviation from the linear relationship assumption between PSA and the log hazard of events. Conclusions: Men with apparently localized prostate cancer and a high baseline PSA value have a reasonable chance of being long-term disease-free when treated with curative intent combining systemic and local therapy. [ABSTRACT FROM AUTHOR]

Using large French retrospective study cohort of chemotherapy-naïve metastatic castration-resistant prostate cancer patients (mCRPC; n = 10,308) in 2014-2018, we described treatment patterns in the 2 years following initiation abiraterone and enzalutamide. Our study suggested similar patterns between abiraterone and enzalutamide initiation: 54% of 65% respectively continued the initial treatment, 14.5% both discontinued active treatments, and about 10% prematurely died. Purpose: Using large French retrospective study cohort of chemotherapy-naïve metastatic castration-resistant prostate cancer patients (mCRPC; n = 10,308) comparing survival between patients who initiated abiraterone (ABI; 64%) and those initiating enzalutamide (ENZ; 36%), the present objective was to describe treatment patterns in the 2 years following initiation. Method: Using the national health data system (SNDS) from 2014 to 2018, we first explored the number of treatment lines, and secondly, patterns of patient management using state sequence analysis; cluster analyses were performed on the 0 to 12 month and 13 to 24 month periods. Age, Charlson score, and duration of androgen deprivation therapy (ADT) were obtained for each cluster in the first year of follow-up. Results: Patients with only 1 treatment line accounted for 52%. In the 0 to 12 month sequence analysis, the main clusters among ABI/ENZ new users involved patients who continued the initial treatment (54% of 65% respectively) and discontinued active treatment (14.5% for both). Less than 2 years exposure to ADT prior to ABI/ENZ initiation was frequently observed for noncontrolled mCRPC, as shown in the death and switch from ABI/ENZ to docetaxel clusters. The clusters for a switch ABI/ENZ to ENZ/ABI involved 6% to 11% of the patients. Conclusion: Our study suggested fairly similar patterns between ABI and ENZ initiation. The cluster of patients with active treatment discontinuation needs to be further investigated, as well as factors influencing therapeutic choice. Better understanding for the use of second-generation hormone therapy in mCRPC in real life, could improve its implementation by clinicians in the early stages of prostate cancer. [ABSTRACT FROM AUTHOR]

This study aimed to generate real-world evidence among older patients with metastatic castration-resistant prostate cancer (mCRPC). Results showed high attrition from first-line therapy (1L) to subsequent lines of therapy. Median time to next treatment or death was < 1 year and median overall survival was < 2 years. These results highlight a need to introduce more effective mCRPC therapies in first-line for older patients. Background: Prostate cancer (PC) is more likely to develop in men =65 years old than in those < 65 years old. This study aimed to generate real-world evidence on treatment patterns, clinical outcomes, health care resource utilization (HCRU), and costs among older patients with metastatic castration-resistant PC (mCRPC). Materials and Methods: A claims algorithm based on treatments expected for mCRPC was used to identify men =65 years old with mCRPC in the SEER-Medicare data between 2007 and 2019. The index date was defined as the date of the start of first-line therapy (1L). Treatment patterns and all-cause and PC-specific HCRU and costs were measured in the 12 months preindex period and the postindex follow-up period. Time to next treatment or death (TNTD) and overall survival (OS) were assessed in the follow-up period. Results: A total of 4758 patients met the eligibility cr iter ia and received 1L treatment. Among these 1L patients, 57.4% subsequently received second-line (2L) treatment; among patients receiving 2L treatment, 49.3% subsequently received third-line (3L) treatment. Abiraterone, enzalutamide, and docetaxel were most common regimens in 1L (41.9%, 22.0%, 22.0%, respectively), 2L (33.3%, 32.7%, 13.6%, respectively), and 3L (17.9%, 25.1%, 22.3%, respectively). On average, patients had 1.2 inpatient admissions, 1.1 emergency room visits, and 27.6 outpatient visits per year during follow-up. The mean total all-cause and PC-related costs during the follow-up period were $111,060 and $99,540 per-patient-per-year, respectively. Median TNTD was 9.3, 6.5, and 5.7 months for 1L, 2L, and 3L, respectively. Median OS from the start of 1L treatment for mCRPC was 21.5 months. Discussion: Among older patients with mCRPC, high attrition from 1L to subsequent lines of therapy was observed. Median TNTD was < 1 year and median OS was < 2 years. These results highlight a need to introduce more effective mCRPC therapies in 1L to improve clinical outcomes for older patients. [ABSTRACT FROM AUTHOR]

A retrospective study compared the oncologic and functional outcomes of salvage cryotherapy (SCT) after primary radiotherapy (XRT-SCT) and cryotherapy (CRYO-SCT). Survival analysis showed no difference in biochemical progression-free survival between cohorts at 2 and 5 years, and comparable functional outcomes, supporting that SCT may be used to treat local prostate cancer recurrence after XRT or Cryotherapy. Introduction: Local prostate cancer recurrence following radiotherapy (XRT) or cryoablation (CRYO) may be addressed with salvage cryotherapy (SCT), although little is known about how the primary treatment modality affects SCT results. Oncologic and functional outcomes of patients who underwent SCT after primary XRT (XRT-SCT) or cryoablation (CRYO-SCT) were studied. Methods: Data was collected using the Duke Prostate Cancer database and the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression-free survival (BPFS). Urinary incontinence, rectourethral fistula, and erectile dysfunction were secondary outcomes. The Kaplan-Meier log-rank test and univariable/multivariable Cox proportional hazards (CPH) models were utilized to evaluate BPFS between groups. Results: 419 XRT-SCT and 63 CRYO-SCT patients met inclusion cr iter ia, that was reduced to 63 patients in each cohort after propensity matching. There was no difference in BPFS at 2 and 5 years both before (P = .5 and P = .7) and after matching (P = .6 and P = .3). On multivariable CPH, BPFS was comparable between treatment groups (CRYO-SCT, HR = 1.1, [0.2-2.2]). On the same analysis, BPFS was lower in D'Amico high-risk (HR 3.2, P < .01) and intermediate-risk (HR 1.95, P < .05) categories compared to low-risk. There was no significant difference in functional outcomes between cohorts. Conclusion: Following primary cryotherapy, salvage cryoablation provides comparable intermediate oncological outcomes and functional outcomes compared to primary radiotherapy. [ABSTRACT FROM AUTHOR]

Preoperative individual risk assessment together with appropriate imaging incorporating Ga-68 PSMA PET is very important in decision-making for the extent of the nerve sparing and keeping the margins tumor-free during a RARP. Neurosafe procedure led to more preserved keeping the margins tumor-free during a RARP. Neurosafe procedure led to more preserved and preoperative extracapsular extension suspicion in imaging together. Background: We aimed to analyze the effect of preoperative risk assessment including Ga-68 PSMA PET and multiparametric magnetic resonance imaging (mpMRI) on nerve sparing practices, positive surgical margin (PSM) rates and oncological outcomes based on a comparison between patients underwent RARP with and without Neurosafe (NS). Methods: Patients underwent RARP with NS (RARP-NS) or without (RARP-only) NS retrospectively evaluated. Suspicion for extracapsular extension on mpMRI and/or Ga-68 PSMA PET was recorded as i(imaging)T3. NS was performed according to the Martini-Klinik technique. PSM at preserved bundle side were called PSM at region of interest (ROI) while the others were elsewhere. Results: A total of 208 patients (90 in RARP-NS, 118 in RARP-only groups) were included. Preoperatively the RARP-only group showed significantly higher mean PSA (p = .01) and PIRADS 5 (p = .002) findings and had more D'Amico high risk (DAHR) patients (p = .08). The overall PSM rates for pT2 versus pT3 disease were 7.5% versus 21.6 and 15.6% versus 55% in RARP-NS and RARP-only groups, respectively. NS resulted in more bilaterally preserved bundles (81.1% vs. 66.3%) and less PSM at the ROI (3.3% vs. 23.4%) than RARP-only group. NS outperformed RARP-only in all clinical settings had its highest differential benefit in more bilateral nerve sparing and less PSM at ROI in patients with both DAHR and iT3 disease. BCR rates were 2.2% and 2.5% for RARP-NS and RARP only groups, respectively (p = .4). One patient in RARP-NS and 9 in RARP-only groups had PSA persistence (p = .02). Conclusion: RARP-NS led to more preserved bundles with less PSM. It was especially useful in DAHR patients with preoperative extracapsular extension suspicion in imaging simultaneously. [ABSTRACT FROM AUTHOR]

There is a paucity of data regarding the management and outcomes of people living with HIV/AIDS (PLWHA) diagnosed with prostate cancer (PCa). This study aims to evaluate the clinicopathological characteristics, progression-free survival (PFS), and overall survival (OS). The study reveals that HIV-positive patients with PCa had comparable PFS and OS to published rates observed in the general population. Introduction: We aimed to characterize the clinicopathological characteristics and outcomes of HIV-positive patients with clinically localized, prostate cancer (PCa). Methods: A retrospective study was conducted of HIV-positive patients from a single institution with elevated PSA and diagnosis of PCa by biopsy. PCa features, HIV characteristics, treatment type, toxicities, and outcomes were analyzed by descriptive statistics. Kaplan-Meier analysis was used to determine progression-free survival (PFS). Results: Seventy-nine HIV-positive patients were included with a median age at PCa diagnosis of 61 years-old and median duration from HIV infection to PCa diagnosis of 21 years. The median PSA level at diagnosis and Gleason Score was 6.85 ng/mL and 7, respectively. The 5-year PFS was 82.5% with the lowest sur vival obser ved in patients treated with radical prostatectomy (RP) + radiation therapy (RT), followed by cryosurgery (CS). There were no reports of PCa-specific deaths, and the 5-year overall survival was 97.5%. CD4 count declined post-treatment in pooled treatment groups that included RT (P = .02). Conclusion: We present the characteristics and outcomes of the largest cohort of HIV-positive men with prostate cancer in published literature. RP and RT ± ADT is well-tolerated in HIV-positive patients with PCa as seen by the adequate biochemical control and mild toxicity. CS resulted in worse PFS compared to alternative treatments for patients within the same PCa risk group. A decline in CD4 counts was observed in patients treated RT, and further studies are needed to investigate this relationship. Our findings support the use of standard-of-care treatment for localized PCa in HIV-positive patients. [ABSTRACT FROM AUTHOR]

Introduction: While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration. Methods: We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all-and high-grade (grade = 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids. Results: Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC. Conclusions: The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling. [ABSTRACT FROM AUTHOR]

We describe the frequency of DNA repair gene pathogenic variants among Mexican men with prostate cancer. We found a low prevalence of known associated germline pathogenic variants in this population. Our results suggest that the genetic and/or epidemiologic risk factors for prostate cancer are not well characterized in this population. Background: Early identification of germline mutation carriers may be relevant for the optimal management of prostate cancer and to inform cancer risk in relatives. However, population minorities have limited access to genetic testing. The aim of this study was to describe the frequency of DNA repair gene pathogenic variants (PVs) among Mexican men with prostate cancer referred for Genomic Cancer Risk Assessment and testing. Methods: Patients diagnosed with prostate cancer who meet cr iter ia for genetic testing and enrolled in the Clinical Cancer Genomics Community Research Network at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City were included. Descriptive statistics were performed using frequency and proportions for categor ical var iables and median and range for quantitative variables. X 2 and t test were used for group comparisons. Results: A total of 199 men were enrolled, median age at diagnosis was 66 (range 44-88) years; 45% were de novo metastatic and 44% were high-very high and 10% were intermediate risk group. Four (2%) had a pathogenic germline variant; one each of the following genes: ATM, CHEK2, BRIP1, and MUTYH (all monoallelic). Younger men at diagnosis were more likely to carry a PV than older age at diagnosis (56.7 vs. 66.4 years, P = .01). Conclusion: Our results showed a low prevalence of known prostate cancer associated PVs and no BRCA PVs in Mexican men with prostate cancer. This suggests that the genetic and/or epidemiologic risk factors for prostate cancer are not well characterized in this specific population. [ABSTRACT FROM AUTHOR]

We assessed the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2014 and December 2022.Considering the MACE safety profile, enzalutamide may be a better choice for prostate cancer. This needs to be further confirmed by larger prospective studies and longer follow-up periods. Background: The potential cardiovascular adverse events associated with new-generation androgen receptor pathway inhibitors (ARPI) in the treatment of prostate cancer remain unclear. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to newgeneration ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We analyzed reports of cardiovascular adverse events associated with drug therapy for prostate cancer submitted to FAERS between January 2014 and December 2022. Three primary new-generation ARPIs were identified: abiraterone acetate, enzalutamide, and apalutamide. Our primary composite endpoint was the PV of MACE caused by ARPIs in the treatment of prostate cancer, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. Results: A total of 278,031 suspected drug-adverse event pairs related to drug treatment in patients with prostate cancer were identified, of which 10,861 reports were cardiovascular events, including 5800 reports of MACE and 5061 reports of other cardiovascular events. The majority of these cardiovascular adverse event reports came from the United States (36.6%) and were mostly older men (age 76.0 ± 8.6 years). Compared with enzalutamide, the constituent ratio of MACE caused by abiraterone acetate and apalutamide was significantly increased, but the incidence of severe MACE decreased significantly. The PV signal regarding MACE was detected in abiraterone acetate and apalutamide but not in enzalutamide. Conclusion: Abiraterone acetate and apalutamide presumably are associated with a higher risk of MACE than enzalutamide in new-generation ARPI for prostate cancer. More extensive prospective studies and more extended follow-up periods need to confirm this further. [ABSTRACT FROM AUTHOR]

Purpose: Contemporary treatment strategies for localized prostate cancer (PCa) have been evolved over time. However, there is little data regarding survival outcomes based on initial treatment by risk group in this new era. This study aims to evaluate survival outcomes among men who underwent observation, radiotherapy, or radical prostatectomy for localized PCa using a population-based cohort. Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) prostate with watchful waiting dataset (2010– 2016) was used. We included men diagnosed with localized PCa and clinical stage T1c-2cN0M0. Other inclusion criteria were age 50–79 years, prostate-specific antigen (PSA) ≤50 ng/mL, and initial treatment with observation (active surveillance/ watchful waiting), radiotherapy, or radical prostatectomy. PCa risk was assessed using the D’Amico classification. The primary endpoint was overall survival. Secondary endpoints included PCa-specific survival. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression and competing risk analysis were performed to assess outcomes. Results: After IPTW-adjusting, pseudo-population comprised 521,656 men (observation: 170,428, radiotherapy: 175,628, radical prostatectomy: 175,600) at a median 36.5 month follow-up. Observation demonstrated the lowest 5-year overall survival rate (91.6%) after IPTW-adjusting in comparison to radiotherapy (92.4%) and radical prostatectomy (96.1%, p<0.001). Men who underwent radical prostatectomy had the lowest cumulative PCa-specific and all-cause mortality (p<0.001). Compared to observation, radiotherapy (sub-distribution hazard ratio [sHR], 0.89; 95% CI, 0.81–0.97; p=0.012) and radical prostatectomy (sHR, 0.46; 95% CI, 0.41–0.52; p<.001) had a lower risk of PCa-specific mortality in competing risk analysis after adjustment for all other factors and other-cause death. Conclusions: Intermediate-term mortality risk in men with localized PCa were lower with active treatments compared to observation - especially for intermediate- and high-risk disease. However, observation represents a safe management strategy in men within the low-risk group. [ABSTRACT FROM AUTHOR]

The introduction of novel therapeutic agents for advanced prostate cancer has led to a wide range of treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC). In the past decade, new treatment options for mCRPC, including abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, radium-223, 177Lu-PSMA-617, and Olaparib, have demonstrated a survival benefit in phase 3 trials. Bone-modifying agents have become part of the overall treatment strategy for mCRPC, in which denosumab and zoledronic acid reduce skeletal-related events. Recently, androgen receptor-signaling inhibitors (ARSIs) and docetaxel have been used upfront against metastatic castration-sensitive prostate cancer. Further, triplet therapy with ARSI, docetaxel, and androgen deprivation therapy is emerging. However, cross-resistance may occur between these treatments, and the optimal treatment sequence must be considered. The sequential administration of ARSIs, such as abiraterone and enzalutamide, is associated with limited efficacy; however, cabazitaxel is effective for patients with mCRPC who were previously treated with docetaxel and had disease progression during treatment with ARSI. Radioligand therapy with 177Lu-PSMA-617 is a new effective class of therapy for patients with advanced PSMA-positive mCRPC. Tumors with gene alterations that affect homologous recombination repair, such as BRCA1 and BRCA2 alterations, are sensitive to poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitors in mCRPC. This review sought to highlight recent advances in systemic therapy for mCRPC and strategies to support patient selection and treatment sequencing. [ABSTRACT FROM AUTHOR]

The human gut microbiota changes under the influence of environmental and genetic factors, affecting human health. Extensive studies have revealed that the gut microbiome is closely associated with many non-intestinal diseases. Among these, the influence of the gut microbiome on cancer biology and the efficacy of cancer therapy has attracted much attention. Prostate cancer cells are affected by direct contact with the microbiota of local tissues and urine, and a relationship between prostate cancer cells and the gut microbiota has been suggested. In the human gut microbiota, bacterial composition differs depending on prostate cancer characteristics, such as histological grade and castration resistance. Moreover, the involvement of several intestinal bacteria in testosterone metabolism has been demonstrated, suggesting that they may affect prostate cancer progression and treatment through this mechanism. Basic research indicates that the gut microbiome also plays an important role in the underlying biology of prostate cancer through multiple mechanisms owing to the activity of microbial-derived metabolites and components. In this review, we describe the evidence surrounding the emerging relationship between the gut microbiome and prostate cancer, termed the “gut-prostate axis.” [ABSTRACT FROM AUTHOR]

The article compares two surgical procedures, Robotic Assisted Simple Prostatectomy (RASP) and Holmium Laser Enucleation of the Prostate (HoLEP), for the treatment of huge Benign Prostatic Hyperplasia (BPH). The study finds that RASP offers advantages over HoLEP, including a wider field of view, easier access, and the ability to perform sophisticated procedures. RASP also reduces complications related to urethral stenosis and sphincter damage. However, HoLEP has shorter hospitalization and lower costs, making it more economically advantageous. The choice of surgery may depend on factors such as patient age, insurance coverage, and the size of the prostate. [Extracted from the article]

Objectives: Prostate cancer (PCa) is among the most frequently diagnosed cancers and a leading cause of cancer-related deaths in men. Although prostate-specific antigen (PSA) testing has become routine in screening and early detection, PSA has high false-positive rates and poorly correlates with disease stage. Consequently, other diagnostic and prognostic markers for PCa are urgently needed. MicroRNAs (miRNAs) modulate gene expression at the transcriptional level and are known to play key roles in various physiological events. Growing evidence indicates that miRNA dysregulation is involved in the initiation and progression of many diseases, including PCa. Various miRNAs have been associated with PCa pathogenesis, suggesting that miRNA expression profiles have potential utility in the prognosis, diagnosis, and treatment of this disease. miRNA expression levels have been investigated in prostate epithelial cells by PCa cell culture. Methods: The present study compared the expression levels of selected prognostic miRNAs targeting that have been implicated in the pathogenesis of PCa. Using cDNA obtained from the C4-2 human PCa and PNT1a normal prostate epithelial cell lines, miRNA expression levels were quantitatively analyzed via melting curve analysis using the miScript SYBR Green kit in a Rotor-Gene Q real-time polymerase chain reaction (PCR) device. Results: Reverse transcription quantitative PCR analyses have demonstrated miRNA expression levels in the C4-2 PCa cell line and PNT1a prostate epithelial cell line. MiR-125, -145, -200, and -222 were found to be overexpressed in the PCa cell line (p<0.05), while there were no statistically significant differences in miR-32 expression of miR-21, -26, Let-7, -34, or -221 between PCa cells and PNT1a cells (p>0.05). Conclusion: Considering the variation in expression level of miRNAs targeting genes responsible for the etiopathogenesis of PCa. Provides information on the use of miRNAs as prognostic markers in PCa. [ABSTRACT FROM AUTHOR]

Considering the importance of immunotoxins in the treatment of patients with prostate cancer, this study aims to summarize the findings of preclinical studies related to the types of immunotoxins used in the treatment of prostate cancer and finally, the suggestions for the treatment of any of these disease was better in the future. It seems that the important keys to success in the treatment with immunotoxins are the specificity of the target antigen and the internalization of the antigen-antibody complex to the cells that express the target antigens. Immunotherapy has long been important in advanced and treatment-resistant prostate cancer due to its anatomical location and sensitivity to immunotherapy agents. Among immunotherapy agents, satisfactory results have been obtained with monoclonal antibodies and scFv conjugated to toxins in preclinical studies. But so far, clinical trials with immunotoxins for prostate cancer have not been reported. Several antibodies that target antigens related to prostate cancer have been effective in preclinical and clinical development. Among these antibodies, anti-PSMA, PSCA, and epidermal growth factor receptor antibodies can be mentioned. Among the target antigens of prostate cancer, PSMA is known for its excessive expression and rapid internalization. It has become clear that both in active immunotherapy (vaccination) and in passive immunotherapy (monoclonal antibody), targeting multiple antigens simultaneously increases the efficacy of treatment in CRPC. Therefore, it is suggested that in future studies, several membrane-specific antigens of prostate cancer should be targeted by immunotoxins. [ABSTRACT FROM AUTHOR]

Wnt/β-catenin signaling is a pathway involved in epigenetics and cancer, regulating cell processes and malignancy in prostate cancer cells. Additionally, Wnt/β-catenin signaling is influenced by epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs. Therefore, targeting both Wnt/β-catenin signaling and epigenetics could be a promising strategy for prostate cancer therapy. Blepharis persica (B. persica) is a plant containing phenolic and flavonoid compounds known for their anti-cancer properties. However, the mechanisms behind its action remain unclear. In this study, we examined the effects of B. persica extract on Wnt/β-catenin signaling in prostate cancer cells (PC-3). To evaluate the cytotoxicity, composition, gene expression, and protein-ligand interactions of the B. persica extract on PC-3 cells, we employed the MTT assay, GC-MS, RT-qPCR, and molecular docking techniques. Our findings indicated that B. persica extract reduced the viability of PC-3 cells, down-regulated Wnt target genes ( CTNNB1 and SNAIL), and up-regulated Wnt antagonists ( APC and AXIN). Furthermore, we identified four B. persica compounds that exhibited the ability to inhibit FZD7, a Wnt receptor. Taken together, these results suggest that B. persica extract can modulate Wnt/β- catenin signaling and epigenetics in PC-3 cells, potentially offering therapeutic benefits. [ABSTRACT FROM AUTHOR]

Partial gland ablation (PGA) is an emerging treatment approach for men with intermediate-risk prostate cancer. However, the patient selection remains a challenge as pretreatment risk stratification does that always capture the true extent of disease, especially in men with intermediate-risk disease. Using nationally representative data we found that men with intermediate-risk prostate cancer who underwent radical prostatectomy had rates of adverse pathology of over 30%. This has important implication for men considering PGA as they may be undertreated. Purpose: Using nationally representative data, we determined the likelihood of adverse pathology at radical prostatectomy (RP) to better inform case selection for partial gland ablation (PGA). Materials and Methods: We identified men with clinically localized GG2 (n = 106,048) and GG3 (n = 55,488) prostate cancer on biopsy from 2010 through 2019 who subsequently underwent RP. Men with GG2 were stratified as unfavorable and favorable per NCCN guidelines. RP adverse pathology was defined as upgrading to GG4-5, pT3-4, or nodal involvement (pN1), respectively. Logistic regression determined factors associated with adverse pathology, and the Cochran-Armitage Test was used to evaluate temporal trends. Results: Men with biopsy GG3 vs. GG2 experienced significant upgrading (11.3% vs. 3.6%, P < .001), more EPE (26.9% vs. 21.1%), SVI (11.9% vs. 5.3%), and pN1 (4.3% vs. 1.6%), all P < .001. When comparing unfavorable vs. favorable GG2, men experienced more EPE (25.3% vs. 16.5%), SVI (7.2% vs. 3%), and pN1 (2.2% vs. 0.8%), all P < .001. In adjusted analysis, age, Hispanic race, PSA > 10 ng/mL, and = 50% positive biopsy cores were associated with adverse pathology (all P < .001). The likelihood of RP adverse pathology for men with biopsy GG3 increased significantly during the study period from 38.8% in 2010 to 47.3% in 2019 (P < .001). Conclusion: Approximately 40% of men with GG3 and more than 30% with unfavorable GG2 prostate cancer harbor adverse pathology that may not be curable by PGA. Given MRI often understages prostate cancer, our findings have significant implications for optimizing PGA case selection and cancer control outcomes. [ABSTRACT FROM AUTHOR]

Metastatic neuroendocrine prostate cancer (NEPC) is a rare, aggressive disease with limited data on secondline treatment. In this retrospective, multi-institutional study, clinical and treatment data were collected for 58 patients with NEPC who received second-line systemic therapy after first-line platinum. Treatments were highly varied but uniformly poor in improving survival. Further study and consensus are needed for second-line NEPC treatment. Background: De novo neuroendocrine prostate cancer (NEPC) and treatment-emergent neuroendocrine prostate cancer (T-NEPC) are rare diseases with a poor prognosis. After first-line platinum chemotherapy, there is no consensus on second-line treatments. Patients and Methods: Patients with a pathologic diagnosis of de novo NEPC or T-NEPC between 2000 and 2020 who received first-line platinum and any second-line systemic therapy were selected and standardized clinical data was collected via the electronic health record at each institution. The primary endpoint was overall survival (OS) based on second-line therapy. Secondary endpoints included objective response rate (ORR) to second-line therapy, PSA response, and time on treatment. Results: Fifty-eight patients (32 de novo NEPC, 26 TNEPC) from 8 institutions were included. At de novo NEPC or T-NEPC diagnosis, the overall cohort had a median age of 65.0 years (IQR 59.2-70.3) and median PSA of 3.0 ng/dL (IQR 0.6-17.9). Following first-line platinum chemotherapy, 21 patients (36.2%) received platinum chemotherapy, 10 (17.2%) taxane monotherapy, 11 (19.0%) immunotherapy, 10 (17.2%) other chemotherapy, and 6 (16.2%) other systemic therapy. Among 41 evaluable patients, the ORR was 23.5%. The mOS after start of second-line therapy was 7.4 months (95% CI 6.1-11.9). Conclusions: In this retrospective study, patients with de novo NEPC or T-NEPC who received second-line therapy were treated with wide variety of treatment regimens, reflecting the lack of consensus in this setting. Most patients received chemotherapy-based treatments. Overall prognosis was poor and ORR was low in the second line regardless of treatment choice. [ABSTRACT FROM AUTHOR]

Studies have suggested that intraductal carcinoma of the prostate is an aggressive disease entity. We assessed outcomes for patients in the Veterans Health Administration with intraductal carcinoma. Patients with intraductal carcinoma were at higher risk of worse disease and increased risk of biochemical recurrence and metastasis development. Intraductal status is an important prognostic indicator for patients with prostate carcinoma. Purpose: Intraductal carcinoma of the prostate (IDC-P) is a relatively unstudied feature present in some prostate cancer (PC) diagnoses with several studies suggesting associations with higher Gleason scores (GS) and earlier time to biochemical recurrence (BCR) after definitive treatment. We looked to identify cases of IDC-P in the Veterans Health Administration (VHA) database and measure associations between IDC-P and pathological stage, BCR, and metastases. Methods: Patients in the VHA database diagnosed with PC from 2000 to 2017, treated with radical prostatectomy (RP) at the VHA were included in the cohort. BCR was defined as post-RP PSA > 0.2 or administration of androgen deprivation therapy (ADT). Time to event was defined as time from RP to event or censor. Differences in cumulative incidences were assessed through Gray's test. Associations with IDC-P and pathologic features at RP, BCR and metastases were assessed through multivariable logistic and Cox regression models. Results: Of 13,913 patients meeting inclusion cr iter ia, 45 patients had IDC-P. Median follow up was 8.8 years from RP. Multivariable logistic regressions showed patients with IDC-P were more likely to have GS =8 (Odds Ratio (OR) 1.14, P = .009) and higher T stages (T3 or 4 vs. T1 or 2 OR 1.14, P < .001). In total, 4,318 patients experienced a BCR, and 1,252 patients developed metastases of whom 26 and 12, respectively, had IDC-P. On multivariable regression IDC-P was associated with higher risk of BCR (IDC-P Hazard Ratio (HR) 1.71, P = .006) and metastases (HR 2.84, P < .001). Cumulative incidence of metastases at 4 years for IDC-P and non-IDC-P were 15.9% and 5.5% (P < .001) respectively. Conclusions: In this analysis, IDC-P was associated with higher Gleason score at RP, shorter time to BCR, and higher rates of metastases. Further studies are warranted to investigate the molecular underpinnings of IDC-P to better guide treatment strategies for this aggressive disease entity. [ABSTRACT FROM AUTHOR]

This analysis of 2800 Veterans Health Administration patients found that relative to patients with PSADT > 12 months, PSADT =2, > 2-=4, > 4-=6, > 6-=8, and > 8-=10 months had significantly higher metastasis and mortality risk, and healthcare costs. This can help select patients for novel hormonal therapy and who can delay such treatments for nmCRPC. Introduction: In patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), prostate-specific antigen doubling time (PSADT) is associated with risk of metastasis and survival. This study evaluated the association of PSADT with clinical and economic outcomes in a real-world setting among patients with nmCRPC not receiving novel hormonal therapy (NHT), using 2-month PSADT thresholds. Patients and Methods: We retrospectively identified Veterans Health Administration patients with nonmetastatic prostate cancer and =2 PSA increases after medical/surgical castration (2012-2016). The third measurement was the index (CRPC) date. Patients with =3 postindex PSA measurements, including index, were followed until death or =12 months until disenrollment, study end, or death, and grouped into 2-month cohorts based on postindex PSADT. Cox regression models assessed association between PSADT, time to metastasis, and death. Healthcare resource utilization and costs were evaluated. Results: Among 2800 evaluable patients, median follow-up was 30 months and median PSADT was 17 months. Relative to the reference cohort (PSADT > 12 months), all cohorts had significantly higher metastasis risk. PSADT =10-month cohorts had significantly greater mortality risk than the reference; hazard ratios (95% confidence intervals) ranged from 12.3 (9.2, 16.4) in the PSADT =2-month cohort to 1.3 (0.9, 2.0) in the > 10 to =12-month cohort. Total costs were significantly higher for cohorts up to and including the PSADT > 8 to =10-month cohort, than for the reference cohort. Mean per patient per month all-cause medical plus pharmacy costs were $6623, $4768, and $4049 in the PSADT =2-month, > 2 to =4-month cohort, and > 4 to =6-month cohorts, respectively, versus $1911 in the PSADT > 12-month cohort (P < 0.05). Conclusion: Most patients with nmCRPC have PSADT > 12 months and a long natural history. For those with shorter PSADT, the risk of metastasis, death, and costs increased. These data can help select patients for NHT and conversely those who can safely delay NHT for nmCRPC. [ABSTRACT FROM AUTHOR]

There are complex interactions between bone and skeletal muscle. However, the prevention and treatment of treatment-induced osteosarcopenia in men with metastatic castration-resistant prostate cancer focuses predominantly on bone health. In a single-center cohort of 52 patients we demonstrate that bone-targeted Radium-223 therapy does not accelerate sarcopenia, but baseline sarcopenia is associated with poor survival in such patients. Introduction: Osteosarcopenia is the progressive loss of musculoskeletal structure and functionality, contributing to disability and mortality. Despite complex interactions between bone and muscle, osteosarcopenia prevention and treatment in men with metastatic castration-resistant prostate cancer (mCRPC) focuses predominantly on bone health. It is unknown whether Radium-223 (Ra-223) therapy affects sarcopenia. Methods: We identified 52 patients with mCRPC who had received Ra-223 and had a baseline plus =1 follow-up abdominopelvic CT scan. The total contour area (TCA) and averaged Hounsfield units (HU) of the left and right psoas muscles were obtained at the inferior L3 endplate, and the psoas muscle index (PMI) was calculated there from. Intrapatient musculoskeletal changes were analyzed across various time points. Results: TCA and PMI gradually declined over the study period (P = .002, P = .003, respectively), but Ra-223 therapy did not accelerate sarcopenia, nor the decline of HU compared to the pre-Ra-223 period. The median overall survival of patients with baseline sarcopenia was numerically worse (14.93 vs. 23.23 months, HR 0.612, P = .198). Conclusions: Ra-223 does not accelerate sarcopenia. Thus, worsening muscle parameters in men with mCRPC undergoing Ra-223 therapy are attributable to other factors. Further research is needed to determine whether baseline sarcopenia predicts poor overall survival in such patients. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer (PC) treatment causes sexual dysfunction (SD) and alters fertility, male identity, and intimate relationships with partners. In Japan, little attention has been paid to the importance of providing care for SD associated with PC treatment. This study is aimed at clarifying the care needs of Japanese men regarding SD associated with PC treatment. Methods: One-to-one semi-structured interviews were conducted with 44 PC patients to identify their care needs. Data were analyzed using thematic analysis. Results: Four core categories emerged from the analysis. (1) "Need for empathy from medical staff regarding fear of SD": patients had difficulty confiding in others about their sexual problems, and medical staff involvement in their SD issues was lacking. (2) "Need for information that provides an accurate understanding of SD and coping strategies before deciding on treatment": lack of information about SD in daily life and difficulty understanding information from medical institutions, caused men to regret their treatment. (3) "Need for professional care for individuals and couples affected by SD": men faced loss of intimacy because of their partners' unwillingness to understand their SD issues or tolerate non-sexual relationships. (4) "Need for an environment that facilitates interaction among men to resolve SD issues": men felt lonely and wanted to interact with other patients about their SD concerns. Conclusion: These findings may help form care strategies tailored to these needs and applicable to other societies with strong traditional gender norms. [ABSTRACT FROM AUTHOR]

Heterogeneity exists in positive nodes (pN +) preoperative negative conventional staging (cN0M0) prostate cancer (PCa) men management. We performed a survey to investigate the current opinion on this issue in the European urological community. An acceptable awareness of pN + disease and management was found. pN + PCa was considered as a multifaceted category needing a risk-adapted approach. Expectant compared to immediate upfront management and new imaging modalities are increasingly considered. Introduction: The urological community's opinion over the management of men being found with pathologically positive nodes (pN +) following radical prostatectomy (RP) performed with curative intent after preoperative negative conventional staging (cN0M0) has never been assessed. This remains crucial, especially considering the advent of novel imaging modalities. Our aim was to investigate the current opinion on management of pN + cN0M0 prostate cancer (PCa) in the European urological community. Methods: Following validation, a 31-item survey, complying with the Cherries checklist, was distributed using a web link from December 2021 to April 2022 to 10 urological societies mailing list. Social media (Twitter, Facebook) were also used. Results: We received 253 replies. The majority were Urologists (96.8%), younger than 60 (90.5%); 5.2% did not have access to PET-scans; 78.9% believed pN + is a multifaceted category; 10-years CSS was marked as 71 to 95% by 17.5%. Gold standard management was stated not being ADT by 80.8% and being RT ±ADT by 52.3%. Early sRT ±ADT was considered an option vs. aRT ±ADT by 72.4%. In case of BCR 71% would perform and decide management based on PSMA-PET whilst 3.7% would not perform PSMA-PET. pN + management is still unclear for 77.1%. On multivariate analysis PSMAPET availability related to a lower and higher likelihood of considering aRT ±ADT as standard and of considering early salvage versus aRT respectively (P < .05). Conclusions: The Urological community has an acceptable awareness of pN + disease and management, although it may overestimate disease aggressiveness. The majority consider pN + PCa as a multifaceted category and rely on a riskadapted approach. Expectant compared to immediate upfront management and new imaging modalities are increasingly considered. [ABSTRACT FROM AUTHOR]

In the last decade, a shift has occurred in the treatment of patients with newly diagnosed metastatic prostate cancer (ndMPC) from ADT monotherapy to early combination therapies of ADT with docetaxel or ARTAs. Although the introduction of novel systemic therapies has made more patients eligible for additional treatments, adherence to clinical practice guidelines remains suboptimal. Introduction: To describe the changes in systemic treatments (ST) of synchronous metastatic hormone-sensitive prostate cancer (mHSPC) patients in a "real-world" setting and to explore reasons why contemporary standard of care (SOC) was not administrated to the patient. Patients and methods: Since 2014, we prospectively register mHSPCpatients. Patients were grouped in 4 time periods: group 1 (Time period 1, January 2014-July 2015), group 2 after introduction of docetaxel (Time period 2, August 2015-July 2017), group 3 after introduction of abiraterone acetate (Time period 3, August 2017-February 2018) and group 4 after introduction of apalutamide (Time period 4, March 2018-October 2021). For every time period, we evaluated the initiated additional ST. In case patients received treatment that differed from contemporary SOC according to guidelines, reasons for this difference were explored. Results: In total, 243 patients were included. A progressive decline in ADT monotherapy from 85% to 29% over time was observed. The proportion of patients receiving additional STs increased from 34% to 59%. Forty percent of patients were not treated according to contemporary SOC, but this percentage varied strongly per time period (10%, 67%, 53%, and 32% from time period 1 to time period 4 respectively). Reasons for these variations were heterogenous and varied across the 4 time periods. Patients being unfit for treatment and treating physicians failing to consider additional STs were the most prevalent reasons. The proportion of patients unfit for additional ST decreased from 18% to 4% over time. Conclusion: Use of ADT monotherapy declined gradually after the introduction of additional systemic treatments. The proportion of patients unfit for additional ST declined as more treatments became available. Although compliance to SOC increased over time, these real-world data show that adherence to clinical practice guidelines remains suboptimal. Efforts should be made by clinicians to increase the adherence to practice guidelines. [ABSTRACT FROM AUTHOR]

The local treatment may not effectively improve the prognosis of mPCa patients. Patients with low level PSA underwent local treatment had better OS. Compared with RT, RP could effectively improve the prognosis of mPCa patients. Introduction: In order to identify the impact of local treatment on overall survival (OS) and cancer-specific survival(CSS) in men with mPCa. Materials and methods: Men with mPCa undergoing local treatment by radical prostatectomy (RP), radiotherapy (RT) including beam radiation and brachytherapy or no local treatment identified from Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). To evaluate local therapy impact on OS and CSS in relation to baseline character istics, univar iate and multivar iable Cox regression analysis was used to predict the prognostic value of local therapy in OS and CSS. Results: A total of 902 (25.8%) patients received local treatment and 2598 (74.2%) patients did not receive local treatment in this study. The Kaplan-Meier curves showed that there was significant difference in OS between patients underwent local treatment and patients without local treatment (P = .013) but not in CSS (P = .068). While multivariate Cox regression analysis showed that local treatment may not significantly improve OS(P = .724). In subgroup analysis, Among patients with prostate-specific antigent (PSA) < 10ng/ml, local treatment could significantly improve OS and CSS (all P < .05). Multivariate Cox regression analysis showed that local treatment could be used as an independent prognostic factor to improve OS in mPCa patients with PSA < 10ng/ml (P = .031). Another multivariate Cox regression analysis demonstrated that patients with mPCa undergoing RP had better OS and CSS (all P < .05). Conclusions: Our results showed that local salvage therapy did not seem to be an independent prognostic factor in all mPCa patients, but we found that local therapy can show a better prognosis in patients with lower PSA levels. Compared with RT, patients who had experienced RP may have better prognosis. We still need prospective research to further study the application value of local treatment in mPCa patients. [ABSTRACT FROM AUTHOR]

To characterize the impact of concomitant prostate cancer treatments with use of relugolix in advanced prostate cancer, a subgroup and pharmacokinetic/pharmacodynamic analyses of the HERO study was undertaken. Treatment with relugolix was associated with similar efficacy and safety profiles with and without concomitant enzalutamide or docetaxel. Standard-of-care use of relugolix in combination with these agents is supported by these data. Background: To characterize the impact of concomitant prostate cancer treatments with the use of relugolix, the oral GnRH receptor antagonist, in advanced prostate cancer, a subgroup and phar macokinetic/phar macodynamic analyses of the HERO study was undertaken. Patients and Methods: Overall, 934 patients were randomized 2:1 to receive relugolix 120 mg orally once daily or leuprolide injections every 12 weeks for 48 weeks. In the setting of rising PSA, patients could receive enzalutamide or docetaxel 2 months after study initiation. Assessments included sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks and safety parameters. Subgroups analyzed included patients with or without concomitant enzalutamide or docetaxel. A sensitivity analysis of the primary endpoint was performed excluding patients who received concomitant therapies that may affect testosterone. Pharmacokinetic/pharmacodynamic analyses of 20 participants in the relugolix treatment group assessed the net effect of enzalutamide on exposure to relugolix. Results: Overall, 125 patients (13.4%) took concomitant therapies that could impact testosterone levels. Enzalutamide (n = 23) was the most frequently used therapy in the relugolix (2.7%) and leuprolide groups (1.9%). Docetaxel (n = 13) was used by 1.3% and 1.6% of patients in the relugolix and leuprolide groups, respectively. All other relevant concomitant therapy were used in < 1% of population. Sensitivity analysis showed concomitant therapy did not impact the testosterone levels. Castration rates were similar with and without concomitant use of enzalutamide or docetaxel. No clinically relevant differences in adverse events were observed between subgroups in either treatment group. No differences in relugolix C trough or testosterone concentrations were observed, suggesting that any induction or inhibition properties of enzalutamide on relugolix metabolism result in a neutral net effect on relugolix exposure and testosterone suppression. Conclusion: Treatment with relugolix was associated with similar efficacy and safety profiles with and without concomitant enzalutamide or docetaxel. Standard-of-care use of relugolix in combination with these agents is supported by these data. [ABSTRACT FROM AUTHOR]