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Purpose of Review: Over the last years, there have been striking changes in the management of metastatic hormone-sensitive prostate cancer (mHSPC) based on survival advantage of combining either a new hormonal agent (NHA) or docetaxel (D) with androgen deprivation therapy (ADT). Some of these studies primarily assessing doublet treatment included men who underwent concomitant or sequential treatment with D. Most recently, prospective randomized evidence emerged on this triplet strategy too. We aimed to outline the current data and ongoing trials evaluating the usage of the triplet therapy in male individuals with mHSPC., Recent Findings: Phase III trials PEACE-1 and ARASENS showed that the upfront triplet treatment with ADT+D and either abiraterone acetate or darolutamide outperformed ADT+D in terms of survival, while severe toxicity was mainly driven by D. Importantly, prospective evidence comparing triplet vs. ADT+NHA is still lacking., Summary: Men with de novo high-volume disease benefit most from the triplet, while in cases with metachronous and/or low-volume disease, survival advantage is still disputable. As efficacy of ADT+NHA does not appear to be substantially amplified by combination with D, those men with a more favorable underlying tumor biology might mostly benefit from this doublet, also taking quality-adjusted survival into account., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Focal therapy (FT) is gaining increasing acceptance in the management of localized prostate cancer particularly due to its favorable safety. Preliminary evidence suggests advantageous utilization of local treatment in the field of oligometastatic prostate cancer (OMPC). Since data on the utilization of FT in OMPC are scarce, we sought to summarize available evidence., Methods: For this narrative comprehensive review, we employed PubMed ® , Web of Science™, Embase ® , Scopus ® , and clinicaltrial.gov databases and Google web search engine to seek peer-reviewed articles, published abstracts from international congresses, and ongoing trials in the English language using the terms "prostate cancer", "oligometastatic", "hormone-sensitive", "focal therapy", "focal treatment", "cryotherapy", "ablation", "cancer" as well as "metastasis-directed therapy. We focused on relevant publications on FT utilized in OMPC targeting the primary or metastatic sites as well as completed and ongoing clinical trials., Results: Growing evidence points to distinct differences in the biologic behavior and molecular signaling processes of OMPC as compared to polymetastatic disease (PMPC). No established biomarkers are available to accurately identify OMPC yet, while several candidates are currently under investigation. The evolution of molecular imaging is set to aid in selecting patients benefitting most from local management. Differences between OMPC and PMPC should be considered when designing the optimal therapeutic strategy. While efficacy data for FT in comparison to standard care in OMPC are scarce, longer progression-free survival and time to castration resistance have been demonstrated for bone metastatic prostate cancer with the primary tumor treated by cryosurgery followed by androgen deprivation therapy (ADT) compared to ADT alone., Conclusion: Ongoing research efforts are eagerly awaited to better characterize OMPC and establish customized strategies for patients with this condition., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Incidental prostate cancer (IPCa) is encountered in 10% of surgical procedures for benign prostatic obstruction (BPO). Identification of patients with underlying detrimental prostate cancer is paramount for tailored treatment decision-making, but guideline recommendations for this setting are lacking., Objective: To highlight clinical and histological characteristics related to BPO surgery that may predict IPCa with unfavorable pathology., Design, Setting, and Participants: We included men with IPCa who underwent radical prostatectomy (RP) in the short term after IPCa diagnosis. Two cohorts were built according to final pathology for the RP specimen: unfavorable pathology (International Society of Urological Pathology [ISUP] grade group [GG] ≥3 and/or ≥pT3a and/or pN1) versus favorable pathology., Outcome Measurements and Statistical Analysis: We performed multivariate regression analysis for the endpoint, which was unfavorable pathology for the RP specimen. Using the model estimates for prostate-specific antigen (PSA), ISUP GG, age, and prostate volume, we established a model for estimating the risk of unfavorable histopathology., Results and Limitations: Overall, 112 patients were included in the final assessment. On multivariate analysis, PSA (odds ratio [OR] 1.083, 95% confidence interval [CI] 1.003-1.170; p = 0.042), ISUP GG for the specimen from BPO surgery (OR 3.090; 95% CI 1.129-8.457; p = 0.028), and age (OR 1.121, 95% CI 1.026-1.225; p = 0.012) were independent predictors for unfavorable histopathology. On receiver operating characteristic analysis, the area under the curve was 0.751. A novel calculator was developed to predict adverse pathology for men with IPCa. The study is limited by its retrospective design., Conclusions: For men with IPCa, PSA before surgery for BPO, ISUP GG, and age are independent predictors of unfavorable disease. Our results might improve preoperative risk assessment for patient counseling., Patient Summary: We developed a novel calculator to estimate the risk of underlying detrimental disease in men diagnosed with prostate cancer at surgery for benign prostatic obstruction., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aim: Robot-assisted simple prostatectomy (RASP) is a minimally invasive alternative to open simple prostatectomy in the management of patients with large prostate glands suffering from moderate-to-severe lower urinary tract symptoms (LUTS). Our study aimed to evaluate two transvesical robotic approaches in order to compare functional outcomes and postoperative complications., Materials and Methods: Clinical data from 111 consecutive patients from three tertiary robotic centers were retrospectively collected. Patients were divided into two groups depending on the surgical approach: 58 Retzius sparing and 53 Retzius approach RASP. We evaluated peri-operative outcomes (operating time, blood loss, transfusion rate, length of hospital stay), as well as intra-operative and early complications using a Clavien Dindo scale. Fisher's exact test, chi-square test and Mann-Whitney U test were applied for statistical analyses. A p -value <0.05 was considered statistically significant., Results: Neither subgroup differed significantly in age ( p  = 0.104), Charlson comorbidity index ( p  = 0.088) or prostate volume ( p  = 0.507), total IPSS score (0.763) and Q max ( p  = 0.651). Total complication rates were lower for the Retzius approach subgroup (19 vs 11.9%) without reaching statistical significance in multivariate analysis (HR = 1.21, 95% CI = 0.17 - 8.44, p  = 0.84). No significant differences based on IPSS total score and Q max could be observed between the two subgroups during follow-up., Conclusions: Both RASP approaches provide similar results in terms of functional outcomes and present a good safety profile in the management of large prostatic adenomas. Larger trials are needed in order to establish the indications for each robotic technique.

Objective: To access the feasibility of palliative cystoprostatectomy/pelvic exenteration in patients with bladder/rectal invasion due to prostate cancer (PC)., Patients and Methods: Twenty-five men with cT4 PC were retrospectively identified in the institutional databases of six tertiary referral centers in the last decade. Local invasion was documented by CT or MRI scans and was confirmed by urethrocystoscopy. Oncological therapies, local symptoms, previous local treatments, time from diagnosis to intervention and type of surgical procedure were recorded. Patients were divided into groups: ADT group (12 pts) and 13 pts without any history of previous local/systemic treatments for PCa (nonADT groups). Perioperative complications were classified using the Clavien-Dindo system. Overall survival (OS) was defined as the time from surgery to death from any cause. A Cox regression analysis, stratified for ISUP score and previous hormonal treatment (ADT) was also performed for survival analysis., Results: Ileal conduit was the main urinary diversion in both cohorts. For the entire cohort, complication rate was 44%. No significant differences regarding perioperative complications and complication severity between both subgroups were observed (p = 0.2). Median follow-up was 15 months (range 3-41) for the entire cohort with a median survival of 15 months (95% CI 10.1-19.9). In Cox regression analysis stratified for ISUP score, no statistically significant differences in OS in patients with and without previous ADT before cystectomy or exenteration were observed (HR 3.26, 95% CI 0.62-17.23, p = 0.164)., Conclusion: Palliative cystoprostatectomy and pelvic exenteration represent viable treatment options associated with acceptable morbidity and good short-term survival outcome., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Recently, a plethora of life-prolonging cytotoxic, next-generation hormonal, immunotherapeutical as well as radionuclide therapies has emerged as a standard care for metastasized castration-resistant prostate cancer. Being strikingly effective in cancer control, these novel therapies might in fact exert a beneficial impact on skeletal events. Therefore, combining anticancer drugs with osteoprotective agents might lead to additional clinical advantage but must be weighed against simultaneously exposing patients to serious toxicities. In addition, further survival prolongation by changing treatment paradigm in both metastasized hormone-sensitive and nonmetastatic castration-resistant disease might potentially increase the risk for bone density reduction complications due to a growing efficacy of androgen ablation leading to prolonged exposure. To address both possible indications of combined treatment and to draw practical conclusions, we performed a comprehensive review of the currently available evidence., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Androgen deprivation therapy (ADT) is commonly used as a first-line treatment for locally advanced and metastatic prostatic cancer (Pca). There is no consensus about which alternative treatment should be used after the failure of initial ADT. We aimed to investigate the effect of changes in treatment on PSA and testosterone levels., Material and Methods: A total of 120 patients with an established diagnosis of either locally advanced or metastatic Pca in two different centers. Depending on the type of medical and/or surgical management protocol planned at initial presentation, all cases were divided into three main groups as follows. Group 1 (n: 80) included the patients who underwent medical management during whole follow-up period in whom the initial management protocol was later on switched to another medical treatment with different agents, Group 2 (n: 20) included patients who were initially treated with a medical management protocol and switched to surgical castration during follow-up evaluation and lastly Group 3 (n: 20) included the patients undergoing treated surgical castration as initial treatment modality without any further medical management protocol., Results: Evaluation of our data did clearly demonstrate a statistically significant difference between the initial and final PSA as well as testosterone levels in Group 1 cases. Mean PSA and testosterone levels increased significantly in these cases despite a change in hormonal therapy by using another agent for androgen deprivation. Cases in Group 2 and 3 cases did not show any statistically significant difference with respect to the mean PSA as well as testosterone values during the same follow-up period., Conclusions: Our data clearly indicated that in case of a biochemical progression, switching into another alternative medical treatment was not effective enough in limiting the rising PSA levels in a statistically significant manner when compared with the approaches of switching to surgical castration after initial medical treatment or continuing with regular and close follow-up after initial surgical castration alone.

Objective: To test the expandability of active surveillance (AS) to Gleason score 3+4 cancers by assessing the unfavorable disease risk in a large multi-institutional cohort., Materials and Methods: We performed a retrospective analysis including 2,323 patients with localized Gleason score 3+4 prostate cancer who underwent a radical prostatectomy between 2005 and 2013 from 6 academic centers. We analyzed the rates of biopsy downgrading/upgrading and advanced stage in the overall cohort by employing standardized AS criteria (using biopsy Gleason score 3+4)., Results: The final pathologic Gleason score was 3+3 = 6 in 8%, 3+4 = 7 in 67%, 4+3 = 7 in 20%, and 8 to 10 in 5% cases. The overall rate of unfavorable disease (upgrading or advanced stage or both) was 46%. In multivariable analysis, prostate-specific antigen (PSA) level>10 ng/ml, PSA density (PSAD) >0.15 ng/ml/g, clinical stage >T1, and>2 positive cores were predictors of unfavorable disease. According to the AS criteria used, the risk of unfavorable disease ranged from 30% to 42%. In patients without any risk factor (PSA level≤ 10 ng/ml, PSAD ≤ 0.15 ng/ml/g, T1c, and ≤ 2 positive cores), the unfavorable disease rate was 19%. The main limitations of this study are the retrospective design and nonstandardization of pathologic assessment between centers., Conclusions: Approximately half of patients with biopsy Gleason score 3+4 cancer have unfavorable disease at final pathology. Nevertheless, expanding AS eligibility to these patients may be acceptable provided adherence to strict selection criteria leading to a<20% risk of unfavorable disease. Future tools for selection such as magnetic resonance imaging, early rebiopsy, and serum markers may be especially beneficial in this group of patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)