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Until the 1980s, testosterone suppression for men with advanced prostate cancer was managed surgically, with bilateral orchiectomy, or medically, with diethylstilbestrol, a drug that was associated with a problematic side effect profile. Beginning in the mid-1980s, the U.S. Food and Drug Administration approved the first luteinizing hormone-releasing hormone agonists, which proved effective for suppressing circulating testosterone levels and led to a significant shift away from surgical castration to medical management during the past 25 years. The luteinizing hormone-releasing hormone agonists resulted in a periodic return of noncastrate testosterone levels once the receptor desensitization attenuated and the effect of androgen agonism resumed. Therefore, the introduction of an androgen receptor antagonist (gonadotropin-releasing hormone antagonist) appeared, conceptually at least, to be a preferable alternative. The first such agent, degarelix, has proved to provide rapid testosterone suppression without the initial testosterone surge associated with luteinizing hormone-releasing hormone agonists. Other new agents in early development include a selective and irreversible inhibitor of CYP17, abiraterone, which has shown success in patients with castration-resistant metastatic prostate cancer, and MDV3100, a novel small molecule that acts as an oral nonsteroidal antiandrogen agent. In sum, these latest agents might lead to a paradigm shift in the treatment of patients with advanced prostate cancer; however, additional studies are required to clarify the many questions that remain regarding the optimal use and sequence of these agents. [ABSTRACT FROM AUTHOR]

The Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) is an ongoing longitudinal observational study of current trends in prostate cancer staging and treatment across a spectrum of different treatment facilities in the United States. To date, the study has documented 2 principal findings: (a) a large variation exists in the treatment choices applied to similar patient presentations across the range of facility type, size, and geographic location in the United States; and (b) although it does not seem to make much difference in mortality outcomes which approach—hormonal therapy, radiotherapy, or surgery—is applied to men at low or intermediate risk, a survival benefit exists with surgery for men at high risk. [ABSTRACT FROM AUTHOR]

Bone pain is a well-known quality-of-life detriment for individuals with prostate cancer and is associated with survival. This study expands previous work into racial differences in multiple patient-reported dimensions of pain and the association between baseline and longitudinal pain and mortality. This is a prospective cohort study of individuals with newly diagnosed advanced prostate cancer enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) from 2017 to 2023 at U.S. sites. Differences in four pain scores at study enrollment by race were investigated. Cox proportional hazards models and joint longitudinal survival models were fit for each of the scale scores to estimate HRs and 95% confidence intervals (CI) for the association with all-cause mortality. The cohort included 879 individuals (20% self-identifying as Black) enrolled at 38 U.S. sites. Black participants had worse pain at baseline compared with White participants, most notably a higher average pain rating (mean 3.1 vs. 2.2 on a 10-point scale). For each pain scale, higher pain was associated with higher mortality after adjusting for measures of disease burden, particularly for severe bone pain compared with no pain (HR, 2.47; 95% CI: 1.44-4.22). The association between pain and all-cause mortality was stronger for participants with castration-resistant prostate cancer compared with those with metastatic hormone-sensitive prostate cancer and was similar among Black and White participants. Overall, Black participants reported worse pain than White participants, and more severe pain was associated with higher mortality independent of clinical covariates for all pain scales., Significance: Black participants with advanced prostate cancer reported worse pain than White participants, and more pain was associated with worse survival. More holistic clinical assessments of pain in this population are needed to determine the factors upon which to intervene to improve quality of life and survivorship, particularly for Black individuals., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Purpose: In 2022 the American Urological Association (AUA) requested an Update Literature Review (ULR) to incorporate new evidence generated since the 2020 publication of this guideline. The resulting 2023 Guideline Amendment addresses updated recommendations for patients with advanced prostate cancer., Materials and Methods: The ULR addressed 23 of the original 38 guideline statements and included an abstract-level review of eligible studies published since the 2020 systematic review. Sixteen studies were selected for full text review. The current summary presents the updates made to the Guideline as a result of that new literature., Results: The Advanced Prostate Cancer Panel amended evidence- and consensus-based statements based on an updated review to aid clinicians in the management of patients with advanced prostate cancer. These statements are detailed herein., Conclusion: This Guideline Amendment provides a framework designed to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer with the most current evidence-based information. Further research and publication of high-quality clinical trials will be essential to continue to improve the quality of care for these patients.

Purpose: The summary presented herein represents Part I of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. Please refer to Part II for discussion of the management of castration-resistant disease., Materials and Methods: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles., Results: The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein., Conclusions: This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

Objective: To bridge gaps in translational science and develop the concepts for 2 novel biomarker-driven clinical trials: one in the presurgical setting and the other in the setting of bladder preservation with chemoradiation., Methods and Materials: The National Cancer Institute sponsored a forum, "Novel Neoadjuvant Therapy for Bladder Cancer," which brought leading clinical and laboratory-based scientists together with the advocacy community., Results: The group designed a neoadjuvant clinical trial to compare the clinical efficacy of the two frontline chemotherapy regimens (gemcitabine plus cisplatin versus MVAC) and the ability of a gene expression profiling-based algorithm (CoXEN) to predict complete pathological response. The trial was recently opened under the leadership of the Southwest Oncology Group (SWOG, S1314), receiving support for the biomarker studies from the NCI's BISQFP resource. A second clinical trial was planned that will examine the relationship between expression of the DNA repair protein MRE11 and complete response in patients treated with concurrent 5-fluorouracil/mitomycin C plus radiation., Conclusion: The meeting provided a unique opportunity to launch a collective effort to establish molecular-based therapies for muscle-invasive urothelial cancer. The goal is to use this framework to develop comparable trials with immunotherapy in non-muscle invasive cancers and to exploit the neoadjuvant platform to develop targeted therapy in muscle-invasive disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Exposure to ionizing radiation has been linked to myelodysplastic syndromes (MDS); it is not clear whether therapeutic radiation doses used for prostate cancer pose an increased MDS risk., Methods: We performed a retrospective cohort study of prostate cancer patients diagnosed between 1986 and 2011 at Cleveland Clinic, comparing those who underwent definitive treatment with radical prostatectomy (RP) to radiotherapy either external beam radiotherapy (EBRT) or prostate interstitial brachytherapy (PI) and to population-based registries. Competing risk regression analyses were used to determine the cumulative risk of developing MDS. All statistical tests were two-sided., Results: Of 10924 patients, 5119 (47%) received radiation (n = 2183 [43%] in EBRT group and n = 2936 [57%] in PI group) and 5805 (53%) were treated with RP. Overall, 31 cases of MDS were observed, with age-adjusted incidence rates no higher than in population-based registries. In univariate analyses, advancing age (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.09 to 1.20; P < .001) and radiotherapy exposure (HR = 3.44; 95% CI = 1.41 to 8.37; P = .007) were statistically significantly associated with development of MDS. In multivariable analyses, although advanced age (HR = 1.13; 95% CI = 1.06 to 1.19; P < .001) remained statistically associated with MDS, radiation did not, although a small non-statistically significant trend existed for PI-treated patients. MDS rates were no higher than in population-based registries., Conclusions: With relatively short follow-up, prostate cancer patients definitively treated with radiation did not appear to have a statistically increased risk of subsequent MDS.

Background: There have been no improvements in the treatment of metastatic urothelial cancer in the past several decades. A census of contemporary clinical research in this disease was performed to identify potential barriers and opportunities., Methods: These authors performed a search for clinical trials exploring interventions in muscle-invasive and metastatic urothelial cancer, using the ClinicalTrials.gov registry. Data extracted from the registry included title, recruitment status, interventions, sponsor, phase, enrollment, study design, and study sites., Results: Among 120 eligible trials exploring interventions in muscle-invasive and metastatic urothelial cancer, 73% were phase 2 and 73% were nonrandomized. The majority (63%) involved treatment in the metastatic disease state. The median planned enrollment size per trial was 45 patients (interquartile range, 47 patients). The majority of trials (55%) involved ≤ 3 study sites. Trials most commonly explored interventions in the first-line metastatic (30%) or second-line metastatic (37%) settings. Targeted therapeutics were studied in 58% of the trials. Among 56 trials that completed enrollment, the median time to complete accrual was 50 months (range, 10-109 months), and these trials enrolled a median of 40 patients per trial (interquartile range, 44 patients)., Conclusions: The majority of contemporary clinical trials in muscle-invasive and metastatic urothelial cancer are small, nonrandomized, phase 2 trials involving 1 to 3 study sites. Enhanced communication and collaboration among the urothelial cancer community, and other stakeholders, is needed to facilitate the design and conduct of trials capable of expediting progress in this disease., (Copyright © 2013 American Cancer Society.)

Objective: To determine, in a phase I/II trial, the maximum tolerated dose (MTD), clinical activity and safety of concurrent subcutaneous (s.c.) interleukin-2 (IL-2), interferon-α2b (IFN-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF)., Patients and Methods: Patients with metastatic renal cell carcinoma (RCC) received on a 3+3 trial design escalating doses of s.c. GM-CSF, IL-2 and IFN-α. Dose-limiting toxicities (DLTs) during the first 6-week cycle were used to determine the MTD. A phase II trial was then initiated to determine clinical activity., Results: A total of sixty patients were enrolled in the study (phase I = 31; phase II = 29). Two DLTs were observed (G3 nausea/vomiting and fatigue) and the MTD was determined to be GM-CSF 5.0 µg/kg/day, IL-2 9.0 mIU/m(2)/day and IFN-α 5.0 mU/m(2)/day. Patients received a median (range) of four (one to 11) cycles of therapy. G3 adverse events were reported in 10 of 31 (32%) patients. The overall response rate was 20% (one complete response and 11 partial responses), including patients who were rendered free of disease with surgery. The median progression-free survival and overall survival were 6.0 and 23.4 months, respectively., Conclusions: Immunotherapy with concurrent s.c. GM-CSF, IL-2 and IFN-α is generally well tolerated. The overall response rate observed with this combination continues to show the efficacy of immunotherapy in a selected group of metastatic RCC patients., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Unlabelled: This was a single-agent phase II clinical trial of the antifol piritrexim in patients with advanced transitional cell carcinoma of the bladder., Methods: Patients with previously-treated, advanced urothelial carcinoma were treated with oral piritrexim at a dose of 25 mg three times daily for 5 consecutive days each week for 3 consecutive weeks followed by a 1-week rest period. Courses were repeated every 28 days., Results: Thirty-five patients were enrolled in the study, with 28 patients evaluable for survival and toxicity and 27 evaluable for response., Toxicity: Myelosuppression was the major dose-limiting toxicity, with WHO grade 3/4 thrombocytopenia in 4 patients, granulocytopenia in 1 patient, and anemia in 3 patients. Grade 3 nonhematologic toxicity consisted of neuropathy in 5 patients, hepatotoxicity in 2, nausea in 2, and 1 each with pulmonary toxicity and rash., Efficacy: Of the 27 patients evaluable for response, 2 (7%) achieved an objective response, lasting 112 and 142 days, respectively., Conclusion: Piritrexim has minimal activity in patients with previously treated transitional cell carcinoma of the bladder, regardless of prior exposure to methotrexate, and further evaluation of this compound in this clinical setting is not warranted.