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Objectives: The aim of this study was to perform a budget impact analysis (BIA) of introducing olaparib treatment for adult patients with metastatic castration-resistant prostate cancer in Argentina. Methods: A BIA model was used to estimate the cost difference between the current scenario (without olaparib) and the new scenario (incorporation of olaparib) for a third-party payer over a 5-year time horizon. The budgetary impact is estimated at the national health system level and by healthcare sectors in Argentina. Input parameters were obtained from the literature and validated by local expert opinion. Direct medical costs were obtained from both the Institute for Clinical Effectiveness and Health Policy (IECS) unit cost database and public data in Argentina. The microcosting estimation was used for key variables of the analysis. All costs are reported in US dollars (US$) as for October 2022 (1 US$ = 152.59 Argentine pesos). One-way sensitivity analyses and scenario analyses were conducted to evaluate the model robustness. Results: The incorporation of olaparib, with a wholesale price per pack of US$3176, was associated with a weighted average of the budget impact per member per month (PMPM) of US$0.0191 for the national health system, being slightly higher than the estimated budgeted high impact threshold (US$0.0153). The PMPM budget impact for a 5-year average ranged between US$0.007 (public sector) and US$0.033 (private sector). The duration of treatment with olaparib was the most influential parameter in the budget impact results. Conclusions: The introduction of olaparib for the treatment of metastatic castration-resistant prostate cancer has a high budget impact for Argentina's health system. These findings are informative to support policy decisions aimed to expand the current treatment landscape for prostate cancer. [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]

Introduction: The prostate cancer (PCa) consists the most frequently diagnosed malignancy of urogenital system in males. Traditionally, treatment of localized PCa was based on surgery or radiotherapy while hormonotherapy was used in more advanced stages. However, the implementation of radiolabels has revolutionized the landscape of prostate cancer. Specifically, prostate-specific membrane antigen (PSMA) has been investigated in different aspects of PCa therapeutic era. Areas covered: A literature review is presented about the implications of PSMA radiolabels on prostate cancer treatment. PSMA tracers were initially used as an imaging technique. Afterwards, PSMA labeled with isotopes presenting cytotoxic abilities, such as lutetium-117 and actinium-225, while reports exist about the use of radioligand immunotherapy. Meanwhile, ongoing trials examine the development of novel radionuclides as well as the evolution of the PSMA-targeted ligands. Expert opinion: Currently, PSMA radioligand treatment of prostate cancer is approved in the metastatic stage of the disease. Meanwhile, a variety of trials exist about its possible role in less advanced stages. However, plenty of parameters should be addressed before these implementations, such as PSMA dosage, dosimetry issues, and its safety profile. A future well-designed study with proper patient selection is mandatory to further explore PSMA radioligand theranostics perspectives. [ABSTRACT FROM AUTHOR]

Background: In Retzius-sparing robot-assisted radical prostatectomy (RARP), lymphocele formation is a troublesome complication. The use of peritoneal flaps has emerged as a promising novel technique to tackle this complication. We explored this technique by suturing both the medial peritoneal flaps to each other and keeping them distracted so that the lymphadenectomy beds are left wide open. Objective: To assess the efficacy of our peritoneal distraction technique on lymphocele rates following Retzius-sparing RARP. Materials and Methods: This retrospective study included patients with localized prostate carcinoma who underwent Retzius-sparing RARP with standard pelvic lymph node dissection between May 2014 and September 2022 at Aster Medcity, Kochi, India. Based on the use of the technique, patients were divided into two groups: peritoneal distraction and closed groups. Both groups were matched using the propensity scoring method in a 1:1 ratio. Results: A total of 272 patients were included, of which 89 (32.7%) belonged to the peritoneal distraction group. Although the overall incidence of lymphocele between the two groups were comparable, none of the patients in the peritoneal distraction group required any intervention for lymphocele management, as opposed to 7 patients from the closed group (3.9%; P = 0.015). No significant association was found between lymphocele formation and serum prostate-specific antigen level, Gleason score, and the number of lymph nodes harvested. Conclusions: This study found that peritoneal distraction stitch is a simple and effective technique to reduce the incidence of symptomatic lymphocele that require intervention after Retzius-sparing RARP. [ABSTRACT FROM AUTHOR]

Background/Aim: When hormone therapy (HT) is combined with radiotherapy, understanding the recovery of testosterone levels after the end of HT becomes crucial for considering subsequent therapy. The aim of this study was to determine the factors influencing the time to recovery of testosterone levels after discontinuation of HT and the likelihood of recovery. Patients and Methods: The study included a total of 108 patients with prostate cancer who were treated with GnRH agonist in combination with radiotherapy and followed up for at least 12 months after discontinuation of the GnRH agonist. The presence of recovery of testosterone levels and the time to recovery were investigated. Univariate and multivariate analyses were performed on several factors contributing to testosterone recovery, including age at initiation of HT, and the duration of HT. Results: Testosterone levels recovered in 61 cases (56.5%). The median time to recovery was 14.8 months. There was a significant difference in the recovery of testosterone levels between patients aged ≥71 years and those aged <71 years at the start of HT (p=0.002), and between those who had been on HT for ≥34 months and those for <34 months (p=0.031). In both univariate and multivariate analyses, age at initiation of HT and duration of HT contributed to the recovery of testosterone levels. Conclusion: The rate of recovery of testosterone levels after long-term (median 34.3 months) HT was lower in patients who were older than 71 years at the start of HT. [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]

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]

Nowadays, prostate cancer is one of the most common forms of malignant neoplasms in men all over the world. Against the background of increasing incidence, there is a high mortality rate from prostate cancer, which is associated with an inadequate treatment strategy. Such a high prevalence of prostate cancer requires the development of methods that can ensure early detection of the disease, improve the effectiveness of treatment, and predict the therapeutic effect. Under these circumstances, it becomes crucial to focus on the development of effective diagnostic and therapeutic approaches. Due to the development of molecular genetic methods, a large number of studies have been accumulated on the role of epigenetic regulation of gene activity in cancer development, since it is epigenetic changes that can be detected at the earliest stages of cancer development. The presence of epigenetic aberrations in tumor tissue and correlations with drug resistance suggest new therapeutic approaches. Detection of epigenetic alterations such as CpG island methylation, histone modification, and microRNAs as biomarkers will improve the diagnosis of the disease, and the use of these strategies as targets for therapy will allow for greater personalization of prostate cancer treatment. [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]

Prostate cancer (PCa) is the most common male cancer and is known to affect around one in eight males in the United States. However, it tends to progress slowly and is even curable in the early stages of the disease. Androgen receptor (AR) hyperactivity and overexpression are present in almost all cases of PCa. Targeting AR with androgen receptor signaling inhibitors (ARSIs) has proven effective at slowing tumor progression by chemically castrating the patient. However, this is not a permanent solution, as all tumors treated with ARSIs eventually become castration-resistant PCa (CRPC). This could be due to a myriad of reasons, such as mutated variants of AR, selective pressure from the use of ARSI drugs eliminating cells that express higher AR (AR+), or the activation of alternative pathways. Additionally, mutated variants of AR may bind to precursors or splice variants of androgens and be unaffected by ARSIs; the tumors themselves may produce more androgens, or the tumor cells may become androgen-independent through the alternate pathways. Further treatment is based on a case-to-case basis depending on various clinical or molecular features, such as the patient's performance status, cancer grade or stage, and dynamic changes in prostate-specific antigen. Options include chemotherapy, intensified androgen deprivation therapy, and targeted therapy for specific molecules. Research for more effective approaches to treating CRPC is currently underway. [ABSTRACT FROM AUTHOR]

Introduction and aim. In real life, metastatic castration-resistant prostate cancer patients (mCRPC) had more complex clinical presentation than patients in the COU-AA-302 trial. This study primarily aimed to describe the overall survival of chemotherapy-naive mCRPC treated with abiraterone acetate plus prednisone (AAP). Other relevant outcomes and baseline characteristics of these patients were also evaluated. Material and methods. This retrospective, observational study collected data from chemotherapy-naive mCRPC patients treated with AAP in Vietnam. Kaplan-Meier curves were used to estimate time to treatment failure (TTF), and overall survival (OS). The impact of baseline characteristics on OS was explored using univariate and multivariate Cox proportional hazard models. Results. Data from 65 eligible patients were analyzed. The rate of PSA response was 73.8%, median PSA PFS was 10.5 months (95% CI: 7.4-13.6), median TTF was 15 months (95% CI: 11.1-18.9), and median OS was 24.9 months (95% CI: 18.9-30.9). Shorter OS was significantly associated with a higher Gleason score (≥8), shorter time from ADT start to mCRPC (<12 months), visceral metastases, and <50% PSA decline (p<0.05). Conclusion. Abiraterone acetate plus prednisone is well tolerated and effective for chemotherapy-naive mCRPC patients in clinical practice. Moreover, Gleason score, visceral metastasis, time from ADT start to mCRPC, and PSA response are the independent indicators for predicting the OS of mCRPC patients in both univariate and multivariate analyses. [ABSTRACT FROM AUTHOR]

This review provides an in-depth examination of the role that tumor-associated macrophages (TAMs) play in the progression of prostate cancer (PCa), with a particular focus on the factors influencing the polarization of M1 and M2 macrophages and the implications of targeting these cells for cancer progression. The development and prognosis of PCa are significantly influenced by the behavior of macrophages within the tumor microenvironment. M1 macrophages typically exhibit anti-tumor properties by secreting pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), thereby enhancing the immune response. Conversely, M2 macrophages contribute to tumor cell migration and invasion through the production of factors like arginase-1 (Arg1) and interleukin-10 (IL-10). This review not only explores the diverse factors that affect macrophage polarization but also delves into the potential therapeutic strategies targeting macrophage polarization, including the critical roles of non-coding RNA and exosomes in regulating this process. The polarization state of macrophages is highlighted as a key determinant in PCa progression, offering a novel perspective for clinical treatment. Future research should concentrate on gaining a deeper understanding of the molecular mechanisms underlying macrophage polarization and on developing effective targeted therapeutic strategies. The exploration of the potential of combination therapies to improve treatment efficacy is also emphasized. By emphasizing the importance of macrophages as a therapeutic target in PCa, this review aims to provide valuable insights and research directions for clinicians and researchers.

Introduction: Prostate cancer is one of the most common malignancies affecting men worldwide, which poses a serious health risk due to its high incidence and impact on quality of life. Despite advances in the diagnosis and treatment of this condition, the management of advanced and aggressive forms of the disease remains complex. Aim of the Study: The aim of this study is to review current diagnostic methods, treatment strategies and prognostic factors in prostate cancer, that a particular focus on personalized medicine and multidisciplinary approaches to improve patient outcomes. Materials and Methods: A comprehensive literature review was conducted using PubMed sources and other scientific databases, focusing on currently available publications. The literature available in the PubMed database was reviewed using the following keywords: “prostate cancer” “prostate cancer diagnosis”, “prostate cancer treatment”, “personalized medicine for prostate cancer”, “physical activity in prostate cancer”. The review included studies on prostate cancer epidemiology, pathogenesis, advances in diagnosis, treatment, physical activity and future research directions. Conclusions: Advances in diagnostic technologies and emerging new therapies have significantly improved the prognosis for patients with prostate cancer. However, continued research and commitment to personalized treatment strategies are essential to meet the challenges of advanced disease. Multidisciplinary collaboration and patient-centered care remain key to optimizing outcomes and improving quality of life for prostate cancer patients.

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]

Angiomyolipoma (AML) is a benign mesenchymal tumor, that is composed of thick-walled blood vessels, smooth muscle cells and adipose tissue. They are commonly seen in kidneys, testicles are not a typical location for AML's; many solid testicular tumors are germ cell malignancies. Here we report the sixth testicular AML case in the literature, to our knowledge. An 80-year-old male undergone bilateral orchiectomy with the diagnosis of local invasive prostate cancer, without any testicular symptoms. Pathological analysis demonstrated a tumor, involving nearly the whole left testicle, composed of muscle cells, vessels and fat tissue, diagnosed as testicular AML. In this article our case is reported and we also make a literature review about testicular AML's. [ABSTRACT FROM AUTHOR]

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 starts as a treatable hormone-dependent disease, but often ends in a drug-resistant form called castration-resistant prostate cancer (CRPC). Despite the development of the antiandrogens enzalutamide and abiraterone for CRPC, which target the androgen receptor (AR), drug resistance usually develops within 6 months and metastatic CRPC (mCRPC) leads to lethality. EZH2, found with SUZ12, EED, and RbAP48 in Polycomb repressive complex 2 (PRC2), has emerged as an alternative target for the treatment of deadly mCRPC. Unfortunately, drugs targeting EZH2 have shown limited efficacy in mCRPC. To address these failures, we have developed novel, dual-acting peptide inhibitors of PRC2 that uniquely target the SUZ12 protein component, resulting in the inhibition of both PRC2 canonical and noncanonical functions in prostate cancer. These peptides were found to inhibit not only the EZH2 methylation activity, but also block its positive effect on AR gene expression in prostate cancer cells. Since the peptide effect on AR levels is transcriptional, the inhibitory peptides can block the expression of both full-length AR and its splicing variants including AR-V7, which plays a significant role in the development of drug resistance. This dual-mode action provides the peptides with the capability to kill enzalutamide-resistant CRPC cells. These peptides are also more cytotoxic to prostate cancer cells than the combination of enzalutamide and an EZH2 inhibitory drug, which was recently suggested to be an effective treatment of mCRPC disease. Our data show that such a dual-acting therapeutic approach can be more effective than the existing front-line drug therapies for treating deadly mCRPC. [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]

Background Radium-223 is a bone-seeking, ɑ-emitting radionuclide used to treat men with bone metastases from castration-resistant prostate cancer. Sclerotic bone lesions cannot be evaluated using Response Evaluation Criteria in Solid Tumors. Therefore, imaging response biomarkers are needed. Methods We conducted a phase 2 randomized trial to assess disease response to radium-223. Men with metastatic castration-resistant prostate cancer and bone metastases were randomly allocated to 55 or 88 kBq/kg radium-223 every 4 weeks for 6 cycles. Whole-body diffusion-weighted magnetic resonance imaging (DWI) was performed at baseline, at cycles 2 and 4, and after treatment. The primary endpoint was defined as a 30% increase in global median apparent diffusion coefficient. Results Disease response on DWI was seen in 14 of 36 evaluable patients (39%; 95% confidence interval = 23% to 56%), with marked interpatient and intrapatient heterogeneity of response. There was an association between prostate-specific antigen response and MRI response (odds ratio = 18.5, 95% confidence interval = 1.32 to 258, P  = .013). Mean administered activity of radium-223 per cycle was not associated with global MRI response (P  = .216) but was associated with DWI response using a 5-target-lesion evaluation (P  = .007). In 26 of 36 (72%) patients, new bone metastases, not present at baseline, were seen on DWI scans during radium-223 treatment. Conclusions DWI is useful for assessment of disease response in bone. Response to radium-223 is heterogeneous, both between patients and between different metastases in the same patient. New bone metastases appear during radium-223 treatment. The REASURE trial is registered under ISRCTN17805587. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second incidence of malignant tumors in men worldwide. Its incidence and mortality are increasing year by year. Enhanced expression of Cav1 in prostate cancer has been linked to both proliferation and metastasis of cancer cells, influencing disease progression. Dysregulation of the Cav1 gene shows a notable association with prostate cancer. Nevertheless, there is no systematic review to report about molecular signal mechanism of Cav1 and drug treatment in prostate cancer. This article reviews the structure, physiological and pathological functions of Cav1, the pathogenic signaling pathways involved in prostate cancer, and the current drug treatment of prostate cancer. Cav1 mainly affects the occurrence of prostate cancer through AKT/mTOR, H-RAS/PLCε, CD147/MMPs and other pathways, as well as substance metabolism including lipid metabolism and aerobic glycolysis. Baicalein, simvastatin, triptolide and other drugs can effectively inhibit the growth of prostate cancer. As a biomarker of prostate cancer, Cav1 may provide a potential therapeutic target for the treatment of prostate cancer. [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]

Introduction This study aimed to evaluate cancer-specific (CSM) and other-cause mortality (OCM) in elderly patients with prostate cancer treated with radical prostatectomy (RP) and postoperative radiotherapy (RT). Material and methods The Surveillance, Epidemiology, and End Results (SEER) database was searched for clinically non-metastatic prostate cancer (PCa) treated with RT after RP between 2010 and 2015. Patients were stratified according to age groups and underwent propensity score (PS) matching. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for survival analysis. Results In total, 5385 patients were analysed, including 738 (13.7%) elderly patients (≥70 years old) and 4647 (86.29%) younger individuals. A total of 54 (7.32%) and 69 (9.35%) patients aged ≥70 years died due to PCa and competing reasons, respectively. Among younger patients these included 275 (5.92%) and 208 (4.48%) deaths, respectively. At a median follow-up of 80 months, patients ≥70 years old had significantly shorter OCM (p <0.0001) than PS-matched younger controls without significant impairment of cancer-specific survival when compared to controls (p = 0.19). In CRR analysis older patients were at significantly higher risk of OCM (HR = 2.24, p = 0.0002 and HR = 3.3, p = 0.011 for patients aged ≥70 and ≥75 years, respectively). Simultaneously, the CRR revealed no increased risk of CSM for patients older than 70 and 75 years (HR = 1.2, p = 0.33 and HR = 1.53, p = 0.29, respectively). Conclusions Elderly patients with PCa are at high risk of dying due to competing reasons, which might prevent the survival benefit of RT after RP. Selection for salvage and adjuvant RT in these individuals should be cautious. [ABSTRACT FROM AUTHOR]