This narrative of the history of the Society of Urologic Oncology (SUO) presents the story of the founding and development of this organization and the creation and establishment of its initiatives and programs. It includes a description of how “Urologic Oncology: Seminars and Original Investigations” came to be designated as its “official journal”, thus commemorating the anniversary of the Journal's twenty-five years of publication.

Purpose African Americans experience greater prostate cancer risk and mortality than do Caucasians. An analysis of pooled phase III data suggested differences in overall survival (OS) between African American and Caucasian men receiving sipuleucel-T. We explored this in PROCEED (NCT01306890), an FDA-requested registry in over 1900 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T. Patients and methods OS for patients who received ≥1 sipuleucel-T infusion was compared between African American and Caucasian men using an all patient set and a baseline prostate-specific antigen (PSA)-matched set (two Caucasians to every one African American with baseline PSAs within 10% of each other). Univariable and multivariable analyses were conducted. Survival data were examined using Kaplan–Meier and Cox proportional hazard methodologies. Results Median follow-up was 46.6 months. Overall survival differed between African American and Caucasian men with hazard ratios (HR) of 0.81 (95% confidence interval [CI]: 0.68–0.97, P = 0.03) in the all patient set and 0.70 (95% CI: 0.57–0.86, P < 0.001) in the PSA-matched set. Median OS was longer in African Americans than in Caucasian men for both analysis sets, e.g., 35.3 and 25.8 months, respectively, in the PSA-matched set. Similar results were observed in the all patient set. Differences were larger when treatment began at lower baseline PSA; curves were more similar among patients with higher baseline PSA. In patients with baseline PSA below the median, the HR was 0.52 (95% CI: 0.37–0.72, P < 0.001), with median OS of 54.3 versus 33.4 months. Known prognostic factors and African American race (multivariable analyses; HR: 0.60, 95% CI: 0.48–0.74, P < 0.001) were independently associated with OS. Use of post-sipuleucel-T anticancer interventions was balanced between races. Conclusion In this exploratory analysis of a registry including nearly 12% African American men with mCRPC, OS was significantly different between African Americans and Caucasians, indicating further research is warranted.

Background: Numerous globally approved castration-resistant prostate cancer (CRPC) therapies are available. Enzalutamide and radium 223 (Ra 223) are approved for survival prolongation and ability to delay radiographic progression. Both have markedly different mechanisms of action as well as safety and tolerability profiles. We prospectively investigated their combined safety and tolerability. Patients and Methods: EnzaRadiCate, a phase II investigator-initiated trial, enrolled subjects with metastatic CRPC from 4 United States uro-oncology research sites. Safety assessment included physical examination, Eastern Cooperative Oncology Group status, electrocardiogram results, laboratory values, opioid use, radiographic responses, and adverse events (AEs). Quality of life and pain were assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and the Brief Pain Inventory Short Form (BPI-SF) questionnaires. Results: Thirty-nine subjects completed at least 2 cycles of Ra 223, and 34 (87%) completed all 6 cycles through and the EOT visit. Sixty-one treatment-related AEs were reported by 53.8% of subjects. The most frequent AEs were fatigue (25.6%), nausea (17.9%), and anemia (12.8%). Three subjects experienced non -treatment-related serious AEs. One subject was hospitalized for sepsis, and 2 deaths were attributed to disease progression. Fifteen (38.5%) subjects demonstrated radiographic progression, and 24 (61.5%) subjects had no radiographic progression. Conclusions: Safety and tolerability of combinatorial use of enzalutamide and Ra 223 were demonstrated. Subjects experienced improvements in quality of life and pain, without unexpected toxicities nor increases in falls, fractures, or deaths. Phase III combination trials of Ra 223 with novel oral hormonal agents are ongoing to further evaluate radiographic progression and overall survival benefit. (C) 2020 Elsevier Inc. All rights reserved.

5035 Background: Prostate cancer risk and mortality are higher in AAs versus CAUs. Post-hoc analyses of pooled Phase 3 data (n = 737) suggested substantial OS benefit for AA men receiving sipuleucel-T (n = 33) vs placebo (n = 10) (McLeod 2012). Compared with pooled placebo patients (n = 249), number needed to treat for OS benefit at 3 years was 3 for AAs and 8 for all sipuleucel-T-treated patients (n = 488) (Moses 2019). Herein we analyzed PROCEED (NCT01306890), a large real-world registry, in which all patients received sipuleucel-T. Methods: In PROCEED, 1902 mCRPC patients received ≥1 sipuleucel-T infusion. OS of all AA (n = 221) and CAU (n = 1649) men were compared. Baseline prostate-specific antigen (PSA), the most important prognostic variable for OS after sipuleucel-T (Schellhammer 2013), substantially differed by race. Thus, OS for a PSA-matched cohort (n = 219 AA; n = 438 CAU) was compared and univariable/multivariable analyses were performed. Post-sipuleucel-T use of OS-prolonging anticancer interventions was also assessed. Results: After a median follow-up of 46.6 mo, median OS was 35.2 (all sipuleucel-T-treated AAs) and 29.9 mo (all sipuleucel-T-treated CAUs): HR 0.81, 95% CI 0.68–0.97; P = 0.03. In the PSA-matched cohort, median OS was 35.3 and 25.8 mo, respectively (HR 0.70, 95% CI 0.57–0.86; P < 0.001). Sipuleucel-T-treated AAs with lower baseline PSA had markedly longer median OS vs sipuleucel-T-treated CAUs. Among those with ≤ median baseline PSA (29.48 ng/ml), median OS was 54.3 mo (AA) vs. 33.4 (CAUs); HR 0.52, 95% CI 0.37–0.72; p < 0.001. Along with other known prognostic factors, AA race was independently associated with prolonged OS on detailed multivariable analyses (HR 0.60, 95% CI 0.48–0.74; p < 0.001) and confirmed on sensitivity analyses. Post-sipuleucel-T life-prolonging anti-cancer therapies were balanced between groups. Conclusions: Sipuleucel-T-treated AAs had significantly improved OS vs sipuleucel-T-treated CAUs. This analysis marks the largest known racial difference in OS in response to any therapy for mCRPC, a finding with implications for both prostate cancer pathophysiology and cancer immunotherapy. Clinical trial information: NCT01306890.

Purpose: Antiandrogens inhibit the androgen receptor and have an important role in the treatment of prostate cancer. This review provides a historical perspective on the development and clinical benefit of antiandrogens in the treatment of prostate cancer. Materials and Methods: We searched PubMed (R) for clinical trials with the search terms antiandrogens and prostate cancer combined with drug names for antiandrogens. This article represents a collaboration of clinical investigators who have made critical scientific contributions leading to the approval of antiandrogens for treating patients with prostate cancer. Results: Antiandrogens differ in chemical structure and exert varying efficacy and safety profiles. The unfavorable therapeutic index of steroidal antiandrogens led to replacement by safer nonsteroidal agents. Flutamide, nilutamide and bicalutamide, which were designed to target the androgen receptor, were developed primarily for use in combination with castration to provide combined androgen blockade. Modest clinical benefits were observed with the combination of first generation antiandrogens and castration vs castration alone. With increased knowledge of androgen receptor structure and its biological functions a new generation of antiandrogens without agonist activity was designed to provide more potent inhibition of the androgen receptor. Randomized clinical trials in patients with metastatic, castration resistant prostate cancer showed significant survival benefits, which led to the approval of enzalutamide in August 2012. Apalutamide was recently approved while darolutamide is not yet approved in the United States. These next generation antiandrogens are being actively tested in earlier disease states such as nonmetastatic prostate cancer. Evolving knowledge of resistance mechanisms to androgen receptor targeted treatments will stimulate research and drug discovery for additional compounds. Further testing in nonmetastatic castration resistant prostate cancer as well as castration sensitive disease states will hopefully augment our ability to treat a broader spectrum of patients with prostate cancer. Conclusions: Antiandrogens have already provided important benefits for prostate cancer treatment. Greater knowledge about the structural and functional biology of the androgen receptor in prostate cancer will facilitate further discovery and development of further improved antiandrogens with enhanced clinical activity in patients with advanced metastatic disease. Testing these new agents earlier in the course of prostate cancer may further improve the survival and quality of life of patients with current local and/or systemic treatment modalities.

Between 1960 and 1975, the Veterans Association Cooperative Urological Research Group (VACURG) conducted a series of large randomized trials to test several oestrogenic compounds in varying doses and combinations with regard to their efficacy and safety in the treatment of all stages of prostate cancer 1. The major message conveyed by these trials was the significant cardiovascular morbidity and mortality associated with 5 mg of oral diethylstilbesterol and the adverse impact on overall survival. Much less attention was given to the cancer-specific survival in the oestrogen arms of the study, which prompted the trial statistician to attribute the favourable effect of oestrogen to testosterone-lowering as well as to a direct cytotoxic effect. One half-century later clinical trial investigators in the UK are reevaluating the therapeutic utility of oestrogen delivered via a transdermal rather than an oral route to address and challenge some of the major conclusions of VACURG. The PATCH (Prostate Adenocarcinoma: TransCutaneous Hormone, MRC, PR 09) trial is an ongoing randomized trial comparing transdermal oestrogen with LHRH analogues in men with advanced prostate cancer. Among the critical endpoints will be overall survival, cancer-specific survival, PSA progression and quality of life. Castrate levels of testosterone have been achieved more rapidly in the transdermal oestrogen arm, there is no testosterone flare, and dose escalation may further improve on the 92–93% of patients reaching castrate levels of testosterone. Trial data published thus far have shown that transdermal oestrogen has a significant advantage with regard to maintaining bone health 2. In the present issue of BJUI, Gilbert et al. 3 address quality-of-life outcomes for 700 patients, representing > 80% of the study cohort, who submitted pre-treatment and 6-month post-treatment questionnaires. For all ages, 6-month global quality of life declined in both arms, but to a statistically lesser extent in the transdermal oestrogen arm compared with the LHRHa arm. There was also a statistically lesser decline in physical function and fatigue and sexual interest with transdermal oestrogen. Sexual interest decline was more pronounced for men aged < 70 years. As expected, hot flashes were significantly lower with transdermal oestrogen and were responsible, along with associated sleep disturbances, for a significant component of the quality-of-life decline in the LHRHa arm. Also, as expected, gynecomastia was more frequent with transdermal oestrogen but was associated with a decline in quality of life only in a small minority (8%) of patients who reported ‘very much’ gynecomastia. Only two patients underwent surgery for gynecomastia. For the small percentage of men for whom gynecomastia/dynia is problematic, more frequent employment of subcutaneous mastectomy could be of benefit. The acceptance of gynecomastia is likely to be quite different between cultures and countries. The finding that sexual interest was improved in the transdermal oestrogen arm is substantiated by clinical trials specifically investigating the role of oestrogen in male sexual health. Both oestrogen and testosterone are necessary 4. Endogenous oestrogen in men is derived from testosterone through aromatization. The absence of testosterone translates to the absence of oestrogen. It is beneficial to be only mono-hormone-deprived (testosterone) rather than dual-hormone-deprived (testosterone and oestrogen). Additional benefits associated with oestrogen in the male have been reviewed by Wibowo et al. 5. The previously reported bone health advantage and the current quality-of-life data would appear quite convincing in favour of transdermal oestrogen as a preferred or at least an alternate option for androgen deprivation therapy; however, the association of oestrogen with cardiovascular toxicity has presented a major hurdle. Interestingly, Byar and Corle 1 noted that on initial publication of the cardiovascular morbidity data, physicians were not convinced and were resistant to changing their support of oral diethylstilbesterol therapy. Today, however, the mindset is the polar opposite: a conviction that oestrogen will expose patients to unacceptable cardiovascular morbidity. However, transdermal delivery, which avoids the enterohepatic first pass through the liver circulation, bypasses the coagulopathies associated with oral oestrogen. A previous report from PATCH confirmed that, with 19-month follow-up there is a similar rate of cardiovascular events between the transdermal oestrogen and LHRHa arms 6. Finally, my favourable drift in this summary is based on personal bias that warrants disclosure and explanation. When my prostate cancer became castration-resistant 8 years ago, LHRHa androgen deprivation therapy was replaced by transdermal oestradiol. My impression that the progression to metastatic castration-resistant prostate cancer was slowed is subject to debate, but my quality-of-life improvement is not. I say this with some degree of confidence, based on cycling between the two agents. Initially on switching to transdermal oestradiol from LHRHa I ‘felt better’. Entry into a subsequent clinical trial required discontinuation of oestrogen and replacement with LHRHa. I regressed, and ‘felt worse’. On completion of the trial I discontinued LHRHa, resumed transdermal oestrogen and ‘felt better’ once again. In moving the needle back to the old so that it becomes new again, we are faced with a difficult mindset hurdle. In the case of transdermal oestrogen, I feel, based on quality of life and even perhaps a survival benefit, it is a hurdle well worth exploration. None declared.

No AccessJournal of UrologyLetter to the Editor/Errata1 Mar 2016Re: Should the Urologist Treat Castration Resistant Prostate Cancer? YesM. P. Wirth and M. Froehner J Urol 2015; 194: 286. Paul F. Schellhammer Paul F. SchellhammerPaul F. Schellhammer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.08.106AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Should the Urologist Treat Castration Resistant Prostate Cancer? Yes." The Journal of Urology, 195(3), pp. 803–804 © 2016 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 195Issue 3March 2016Page: 803-804 Advertisement Copyright & Permissions© 2016 by American Urological Association Education and Research, Inc.MetricsAuthor Information Paul F. Schellhammer More articles by this author Expand All Advertisement PDF downloadLoading ...

A urologist's personal experience with multiple surgical, hormonal, and radio/immunotherapeutic options for the treatment of advanced prostate cancer and thoughts on the role of old and new therapies.

PSA screening for prostate cancer is a controversial issue around the world. In this article the authors describe the situation in North America where screening is not being advised. They argue that patients should be tested and that men will adapt and learn to live with the results as active surveillance becomes more acceptable.

PURPOSE:Inaccurate diagnoses of prostate cancer can result from transposition or contamination of patient biopsy specimens, which are known as specimen provenance complications. We assessed the clinical and economic burden of specimen provenance complications in prostate biopsies in the United States.MATERIALS AND METHODS:We performed a comprehensive, systematic review of the literature to approximate the effect of specimen provenance complications on direct medical costs, patient QALYs and medicolegal costs. Data were extracted from published studies on specimen provenance complications rates, prostate cancer treatment efficacy, treatment cost, litigation/settlement costs after false diagnoses of prostate biopsies and patient quality of life. Sensitivity analysis was done to identify factors that most influenced the outcomes and assess the robustness of the findings.RESULTS:Of the estimated 806,251 primary and secondary prostate biopsies performed annually in the United States 20,322 specimen provenance complications were projected to result in 4,570 clinically meaningful false diagnoses and an expected loss of 634 QALYs. The total burden of specimen provenance complications was projected to exceed $879.9 million or $3,776 per positive cancer diagnosis. This estimate was most sensitive to the indemnity cost per false-positive case and the rate of transpositions at independent reference laboratories.CONCLUSIONS:The societal burden of specimen provenance complications in patients who undergo prostate biopsy exceeds $880 million annually in the United States. This analysis framework may be useful as policy makers, health organizations and researchers seek to decrease false diagnoses of prostate cancer and the consequent effects of delayed or unnecessary treatment. Further study is warranted to quantify the economic burden among additional diseases.

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History III1 Apr 2015MP14-02 PROSPECTIVE QUALITY OF LIFE IMPACT ANALYSIS FOLLOWING LOCALIZED PROSTATE CANCER TREATMENTS: BRACHYTHERAPY, CRYOTHERAPY, AND RADICAL PROSTATECTOMY LONG-TERM FOLLOW-UP Matthew Ingham, Arjun Poddar, Mark Shaves, Michael Fabrizio, Raymond Lance, Robert Given, Kurt McCammon, Paul Schellhammer, and Michael Williams Matthew InghamMatthew Ingham More articles by this author , Arjun PoddarArjun Poddar More articles by this author , Mark ShavesMark Shaves More articles by this author , Michael FabrizioMichael Fabrizio More articles by this author , Raymond LanceRaymond Lance More articles by this author , Robert GivenRobert Given More articles by this author , Kurt McCammonKurt McCammon More articles by this author , Paul SchellhammerPaul Schellhammer More articles by this author , and Michael WilliamsMichael Williams More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.864AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A number of treatment modalities for localized prostate cancer (CaP) exist, often with similar oncologic outcomes. As such, health related quality of life (HRQOL) plays a significant role in treatment decisions. We sought to evaluate the long-term HRQOL impact of four such treatments. METHODS Patients undergoing open radical prostatectomy (ORP), robotic assisted prostatectomy (RAP), brachytherapy (BT), or cryotherapy (CRYO) for localized CaP between March 2002 and October 2009 were asked to complete the UCLA-PCI pre-op and at 1, 3, 6, 12, 18, 24, 30, 36, 48, and 60 months post-op. 586 of 1094 patients returned surveys out to the 60-month endpoint. Outcomes were compared across treatment modalities and age cohorts (<60, 60–70, and >70 years). Baseline scores were obtained along with a percent of baseline score (PBS) for all subsequent surveys. RESULTS For urinary function (UF) and bother (UB) domains, those undergoing BT or CRYO showed a significant improvement in HRQOL vs ORP or RAP, which persisted to the 60-month endpoint. BT and CRYO also showed a faster return of HRQOL, plateauing by 6–12 months compared with ORP and RAP which plateaued at 18–24 months (Fig 1). Sexual function (SF) and bother (SB) domains showed a significantly improved HRQOL for BT over ORP, RAP, and CRYO. By 12 months, BT patients had roughly double the improvement of the other groups. BT, however, demonstrated a decline in SF after 36 months vs ORP, RAP, and CRYO which had stable SF over the same period. For patients > 70 years, a near complete return to baseline UF and UB by 12 months was noted which persisted to 60 months vs the younger cohorts whose PBS plateaued at roughly 80. Conversely, at 60 months, SF PBS scores of 53, 41, and 29 were found for the <60, 60–70, and >70 years cohorts, respectively. CONCLUSIONS In this cohort of patients followed to 5 years, BT and CRYO offer durable HRQOL benefits in both UF and UB over ORP and RAP. BT alone offers improved HRQOL outcomes for SF as compared to ORP, RAP, or CRYO. Patients age >70 have an excellent recovery of baseline UF and UB but do poorly with SF recovery as compared to younger cohorts. Certainly, these findings can be employed for appropriate counselling prior to treatment decisions. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e151 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Ingham More articles by this author Arjun Poddar More articles by this author Mark Shaves More articles by this author Michael Fabrizio More articles by this author Raymond Lance More articles by this author Robert Given More articles by this author Kurt McCammon More articles by this author Paul Schellhammer More articles by this author Michael Williams More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Background: Few data exist regarding the impact on survival of definitive treatment of the prostate in men diagnosed with metastatic prostate cancer (mPCa).Objective: To evaluate the survival of men diagnosed with mPCa based on definitive treatment of the prostate.Design, setting, and participants: Men with documented stage IV (M1a-c) PCa at diagnosis identified using Surveillance Epidemiology and End Results (SEER) (2004-2010) and divided based on definitive treatment of the prostate (radical prostatectomy [RP] or brachytherapy [BT]) or no surgery or radiation therapy (NSR).Outcome measurements and statistical analysis: Kaplan-Meier methods were used to calculate overall survival (OS). Multivariable competing risks regression analysis was used to calculate disease-specific survival (DSS) probability and identify factors associated with cause-specific mortality (CSM).Results and limitations: A total of 8185 patients were identified: NSR (n = 7811), RP (n = 245), and BT (n = 129). The 5-yr OS and predicted DSS were each significantly higher in patients undergoing RP (67.4% and 75.8%, respectively) or BT (52.6 and 61.3%, respectively) compared with NSR patients (22.5% and 48.7%, respectively) (p < 0.001). Undergoing RP or BT was each independently associated with decreased CSM (p < 0.01). Similar results were noted regardless of the American Joint Committee on Cancer (AJCC) Mstage. Factors associated with increased CSM in patients undergoing local therapy included AJCC T4 stage, high-grade disease, prostate-specific antigen >= 20 ng/ml, age >= 70 yr, and pelvic lymphadenopathy (p < 0.05). The major limitation of this study was the lack of variables from SEER known to influence survival of patients with mPCa, including treatment with systemic therapy.Conclusions: Definitive treatment of the prostate in men diagnosed with mPCa suggests a survival benefit in this large population-based study. These results should serve as a foundation for future prospective trials.Patient summary: We used a large population-based cancer database to examine survival in men diagnosed with metastatic prostate cancer (mPCa) undergoing definitive therapy for the prostate. Local therapy (LT) appeared to confer a survival benefit. Therefore, we conclude that prospective trials are needed to further evaluate the role of LT in mPCa. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.