Primary Treatment For Localized Prostate Cancer Research Articles

Abstract 3813: Relationship between race/ethnicity and oncologic outcomes in patients with biochemical recurrence after primary treatment for prostate cancer

Abstract Background: Prostate cancer (PC) is the most common form of cancer in men and accounts for ~35% and 24% of all new cancer diagnoses in Black and Hispanic men, respectively. Incidence rates of PC are higher and cancer is diagnosed at a younger age in Black compared to White men. The most frequently utilized primary treatment options are radical prostatectomy (with or without adjuvant radiotherapy) or radiotherapy. Despite the success of primary treatments for localized PC, many patients (pts) will eventually develop biochemical recurrence (BCR), defined as rising prostate-specific antigen (PSA) levels. Pts with BCR are at a higher risk of developing distant metastases and ultimately dying from PC. This targeted literature review aimed to assess the real-world (RW) relationship between race/ethnicity and BCR, and further identify any differences in oncologic outcomes (risk of metastases, PC-specific mortality, and overall survival). Methods: A targeted literature search was performed using Embase, PubMed, and the past 2 years of American Society of Clinical Oncology conference proceedings. Selected studies were limited to English-language articles focusing on BCR and race or ethnicity among US populations, published between 1/2010 and 7/2023. Results: Ten studies were selected after title and abstract review. Most studies had a White pt majority (83%-92%). Six studies reported no differences in BCR or oncologic outcomes when pts were stratified by race/ethnicity. Four studies reported a higher BCR risk for Black pts with low-risk PC after radical prostatectomy, but not for pts with high-risk PC. PSA and PSA doubling time (PSADT) were found to be strong predictors of oncologic outcomes. Conclusions: The FDA draft guidance on diversity plans recommends that clinical trials enroll an adequate number of participants from underrepresented racial and ethnic populations. This requires an understanding of the diversity of the population that will eventually use the treatment and of which race/ethnicity differences in outcomes should be expected and investigated. Based on this targeted review among pts with localized PC, most RW studies had a White pt majority, and the race distribution in these studies aligned with published census and epidemiology data. In addition, findings suggest that race/ethnicity differences were not pronounced among high-risk PC pts in the US when given equal access to care or treatment, and that oncologic outcomes and BCR risk were similar across Black, White, and Hispanic pt populations. Conversely, PSA and PSADT may be stronger prognostic markers for BCR and oncologic outcomes. Future clinical trials are needed to support these RW findings and should aim to actively enroll racial/ethnic minorities to identify potential differences in efficacy and safety, and to help advance the evidence base for pt PC management. Citation Format: Nasreen Khan, Vanessa Quintero, Clara Beck, Miryana Dimova-Dobreva, Binita Patel. Relationship between race/ethnicity and oncologic outcomes in patients with biochemical recurrence after primary treatment for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3813.

Long-term follow-up with a clinical decision support system based on laboratory reports to manage patients with biochemical recurrence after radical prostatectomy

IntroductionCurrently, prostate cancer (PCa) is the second most common cause of cancer death, and radical prostatectomy (RP) remains the primary treatment for localized PCa. Although there is no consensus on an optimal strategy, the determination of total serum prostate-specific antigen (tPSA) is the cornerstone for the detection of postoperative biochemical recurrence (BCR). The aim of this study was to evaluate the prognostic utility of serial tPSA levels together with other clinicopathological factors and to assess the impact of a commentary algorithm implemented in our laboratory information system. MethodsA descriptive and retrospective study of patients with clinically localized PCa who underwent RP. BCR-free survival was calculated over time (Kaplan-Meier analysis), and the ability of different clinicopathological factors to predict BCR was studied (univariate and multivariate analyses) with Cox models. ResultsA total of 203 patients underwent RP, of whom 51 presented with BCR during follow-up. In the multivariate model, doubling of tPSA, the Gleason score, tumour stage and tPSA nadir were detected as independent predictors of BCR. ConclusionA patient with undetectable tPSA after 1959 days of RP is unlikely to develop BCR, regardless of preoperative or pathologic risk factors. Furthermore, doubling of tPSA in the first 2 years of follow-up was the main prognostic factor for BCR in patients undergoing RP. Other prognostic factors included a tPSA nadir detectable after surgery, a Gleason score ≥ 7 and a tumour stage T ≥ 2c.

Patient-reported Satisfaction and Regret Following Focal Therapy for Prostate Cancer: A Prospective Multicenter Evaluation

BackgroundSeveral reports are available regarding the treatment decision regret of patients receiving conventional treatments for localized prostate cancer (PCa); yet data on patients undergoing focal therapy (FT) are sparse. ObjectiveTo evaluate the treatment decision satisfaction and regret among patients who underwent FT for PCa with high-intensity focused ultrasound (HIFU) or cryoablation (CRYO). Design, setting, and participantsWe identified consecutive patients who underwent HIFU or CRYO FT as the primary treatment for localized PCa at three US institutions. A survey with validated questionnaires, including the five-question Decision Regret Scale (DRS), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF-5), was mailed to the patients. The regret score was calculated based on the five items of the DRS, and regret was defined as a DRS score of >25. Outcome measurements and statistical analysisMultivariable logistic regression models were applied to assess the predictors of treatment decision regret. Results and limitationsOf 236 patients, 143 (61%) responded to the survey. Baseline characteristics were similar between responders and nonresponders. During a median (interquartile range) follow-up of 43 (26–68) mo, the treatment decision regret rate was 19.6%. On a multivariable analysis, higher prostate-specific antigen (PSA) at nadir after FT (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.1–2, p = 0.009), presence of PCa on follow-up biopsy (OR 3.98, 95% CI 1.5–10.6, p = 0.006), higher post-FT IPSS (OR 1.18, 95% CI 1.01–1.37, p = 0.03), and newly diagnosed impotence (OR 6.67, 95% CI 1.57–27, p = 0.03) were independent predictors of treatment regret. The type of energy treatment (HIFU/CRYO) was not a predictor of regret/satisfaction. Limitations include retrospective abstraction. ConclusionsFT for localized PCa is well accepted by the patients, with a low regret rate. Higher PSA at nadir, presence of cancer on follow-up biopsy, bothersome postoperative urinary symptoms, and impotence after FT were independent predictors of treatment decision regret. Patient summaryIn this report, we looked at the factors affecting satisfaction and regret in patients with prostate cancer undergoing focal therapy. We found that focal therapy is well accepted by the patients, while presence of cancer on follow-up biopsy as well as bothersome urinary symptoms and sexual dysfunction can predict treatment decision regret.

MP46-18 PATIENTS REPORT SATISFACTION/REGRET FOLLOWING FOCAL THERAPY FOR LOCALIZED PROSTATE CANCER: A PROSPECTIVE MULTICENTER EVALUATION

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy (MP46)1 Sep 2021MP46-18 PATIENTS REPORT SATISFACTION/REGRET FOLLOWING FOCAL THERAPY FOR LOCALIZED PROSTATE CANCER: A PROSPECTIVE MULTICENTER EVALUATION Alireza Ghoreifi, Masatomo Kaneko, Samuel Peretsman, Atsuko Iwata, Aliasger Shakir, Dordaneh Sugano, Jie Cai, Giovanni Cacciamani, Daniel Park, Osamu Ukimura, Duke Bahn, Inderbir Gill, and Andre Luis Abreu Alireza GhoreifiAlireza Ghoreifi More articles by this author , Masatomo KanekoMasatomo Kaneko More articles by this author , Samuel PeretsmanSamuel Peretsman More articles by this author , Atsuko IwataAtsuko Iwata More articles by this author , Aliasger ShakirAliasger Shakir More articles by this author , Dordaneh SuganoDordaneh Sugano More articles by this author , Jie CaiJie Cai More articles by this author , Giovanni CacciamaniGiovanni Cacciamani More articles by this author , Daniel ParkDaniel Park More articles by this author , Osamu UkimuraOsamu Ukimura More articles by this author , Duke BahnDuke Bahn More articles by this author , Inderbir GillInderbir Gill More articles by this author , and Andre Luis AbreuAndre Luis Abreu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002067.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The objective is to evaluate the treatment decision satisfaction and regret among patients who underwent Focal Therapy (FT) for localized prostate cancer (PCa) with high-intensity focused ultrasound (HIFU) or cryoablation (CRYO). METHODS: We identified consecutive patients who underwent hemi-gland HIFU or CRYO FT as primary treatment for localized PCa at three US institutions (IRB# HS-17-00749). A survey with validated questionnaires was mailed between February and December of 2020, including: 5-question Decision Regret Scale (DRS); International Prostate Symptom Score (IPSS); and International Index of Erectile Function (IIEF-5). Potency was defined as IIEF-5 ≥ 18. The regret score was calculated based on the 5 items of DRS (Figure). Agreement with each item is measured on a 5-point scale and the final score is converted to a 0-100 scale. Regret was defined as DRS ≥ 26. Multivariable logistic regression models were applied to assess baseline and post-FT predictors for treatment decision regret. Statistically significant if p<0.05. RESULTS: Out of 236 patients, 143 (61%) responded the survey (71/116 HIFU and 72/120 CRYO). Baseline characteristics were similar between responders and no-responders. For the responders, the median (IQR) follow-up was 43 (26-68) months. The treatment decision regret rate was 19.6%, being CRYO 23.6% vs. HIFU 15.5% (OR 1.7, p=0.22). The Figure shows the details of patients’ responses to each DRS question. Higher PSA at nadir (OR 1.48, 95%CI 1.1-2, p=0.009) post FT, presence of PCa on the follow-up biopsy (OR 3.98, 95%CI 1.5-10.6, p=0.006), higher IPSS after FT (OR 1.18, 95%CI 1.01-1.04, p=0.03), and de-novo impotence (OR 6.67, 95%CI 1.57-27, p=0.03) were independent predictors of treatment decision regret. CONCLUSIONS: Focal therapy for localized PCa is well-accepted by the patients. Higher PSA at nadir, presence of cancer on the follow-up biopsy, higher post-operative IPSS, and de-novo impotence are independent predictors of treatment decision regret. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e820-e821 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alireza Ghoreifi More articles by this author Masatomo Kaneko More articles by this author Samuel Peretsman More articles by this author Atsuko Iwata More articles by this author Aliasger Shakir More articles by this author Dordaneh Sugano More articles by this author Jie Cai More articles by this author Giovanni Cacciamani More articles by this author Daniel Park More articles by this author Osamu Ukimura More articles by this author Duke Bahn More articles by this author Inderbir Gill More articles by this author Andre Luis Abreu More articles by this author Expand All Advertisement Loading ...

Diagnostic utility of (18)f-fluciclovine positron emission tomography (FACBC) in biochemically recurrent (BCR) prostate cancer (PCa) based on prior primary treatment modality for localized disease and the impact of FACBC findings on treatment selection.

34 Background: Management of BCR PCa requires accurate assessment of location and extent of recurrent disease. FACBC has been shown to be a sensitive modality for detection and localization of recurrent disease but treatment guidelines are based on the findings of conventional (conv) imaging, including computed tomography, magnetic resonance imaging, or bone scintigraphy, and little is known about how prior treatment impacts FACBC findings and concordance with conv scans. Methods: This single-center retrospective study included 137 patients (pts) who had FACBC for BCR at the University of Wisconsin-Madison from 10/2017-10/2019. Clinical, pathological, imaging, and treatment data were collected by chart review. Pts were classified by type of primary treatment for localized PCa, either radical prostatectomy (RP) or radiation therapy (RT). Findings of conv scans performed within 4 weeks prior or any time after FACBC were collected. Results: 105 pts had RP and 32 pts had RT as their primary PCa treatment. Gleason score and PSA at diagnosis were similar between groups. Median PSA at time of FACBC was higher in the RT compared to RP group (3.3 vs 0.7 ng/dL) and median time from initial diagnosis to FACBC was longer (70 vs 55 months). Frequency of (+) FACBC findings was higher in the RT group (66% vs 47%); only 3% of pts in the RT group had a (-) FACBC compared to 29% in the RP group. The rate of (+) lesions in the prostate/prostate bed was higher in the RT group (41% vs 22%), while the rate of (+) lesions in pelvic nodes and distant sites was similar between groups. Of 69 pts who also had conv imaging, 61% had concordant conv imaging findings. In the RT group, conv and FACBC findings were similar in 47% of pts and not similar in 28%. In the RP group, conv and FACBC findings were similar in 26% of pts and not similar in 17%. Management after FACBC is listed in table. Median time from FACBC to first (+) conv scans was 6 (range: 0-18) and 5 (range: 0-17) months for RT and RP groups, respectively. Conclusions: In this large retrospective cohort, pts treated with initial RT had a longer median time from diagnosis to FACBC and higher median PSA at the time of FACBC compared to the RP group. RT patients had a higher rate of (+) FACBC findings but were more likely to continue on observation. The median time from FACBC to first (+) conv scan was 5-6 months, supporting the role of FACBC in earlier detection of recurrent disease in both groups of patients. Further analysis of concordance between FACBC and conv imaging is in process. [Table: see text]

Irreversible Electroporation for the Ablation of Prostate Cancer.

Although still considered experimental, focal irreversible electroporation (IRE) as a primary treatment for prostate cancer (PCa) is considered one of the most promising ablative technologies for focal therapy. This review provides a description of the principle of IRE for the treatment of PCa, combined with an overview of the recent research. It has been almost a decade since the first human studies of focal IRE for PCa were trying to demonstrate its feasibility and safety, and recently new data are emerging regarding the functional and oncological outcomes. It was shown that the expected ablation efficacy of IRE is dependent on increased safety margins of > 9mm and an uninterrupted IRE procedure, but these findings need further investigation in larger cohorts and randomized control trials (RCT). Recent data from larger cohorts with a longer follow-up of up to 12months prove that focal IRE as primary treatment for localized PCa is indeed safe, has effective short-term oncological control in selected patients, and it has good functional outcomes by retaining urinary function and causing only mild erectile dysfunction.

Endocrine disrupting-chemicals and biochemical recurrence of prostate cancer after prostatectomy: A cohort study in Guadeloupe (French West Indies).

Previous studies have suggested that exposure to environmental chemicals with hormonal properties, also called endocrine disrupting chemicals, may be involved in the occurrence of prostate cancer (PCa). Such exposure may also influence the treatment outcome as it is still present at the time of diagnosis, the beginning of therapy, and beyond. We followed 326 men in Guadeloupe (French West Indies) who underwent radical prostatectomy as primary treatment of localized PCa. We analyzed the relationship between exposure to the estrogenic chlordecone, the antiandrogenic dichlorodiphenyldichloroethylene (DDE, the main metabolite of the insecticide DDT), and the nondioxin-like polychlorinated biphenyl congener 153 (PCB-153) with mixed estrogenic/antiestrogenic properties and the risk of biochemical recurrence (BCR) after surgery. After a median follow-up of 6.1 years after surgery, we found a significant increase in the risk of BCR, with increasing plasma chlordecone concentration (adjusted hazard ratio = 2.51; 95% confidence interval: 1.39-4.56 for the highest vs. lowest quartile of exposure; p trend = 0.002). We found no associations for DDE or PCB-135. These results shown that exposure to environmental estrogens may negatively influence the outcome of PCa treatment.

Prostatectomie totale de rattrapage après échec de traitement local pour cancer de prostate : morbidité, résultats oncologiques et fonctionnels

Salvage radical prostatectomy (sRP) for radiorecurrent prostate cancer (PCa) is a challenging procedure. To report our experience with sRP for selected patients with local recurrence after primary treatment for localised PCa. From 2005to 2015, 24patients underwent sRP for recurrent PCa in our center and were included in this retrospective study. Local recurrence was suspected by PSA increase>nadir+2ng/mL and was confirmed by biopsy. Perioperative complications according to Clavien-Dindo classification, oncological and functional results were analysed. Overall, 24patients with a median age of 59years (IQR: 55-60) were included. Median follow-up was 25months (IQR: 9-26). Procedures were performed with open-retropubic approach in 50% and robot-assisted laparoscopic approach in 50%. Overall, 5 (21%) and 2 (8%) patients experienced grade≤IIIa and grade≥IIIb postoperative complication, respectively. Surgical margins were positive in 46% of cases. Three out of 4patients with postoperatively detectable PSA (>0.2ng/mL) had positive surgical margins. Seven patients experienced biochemical recurrence in a median delay of 19months (9-62). Seventy-one percent (5) of these patients experienced clinical recurrence in a median delay of 24months (10-113). Severe urinary incontinence (≥3pads/day) and erectile dysfunction were reported in 25% and 63%, respectively. sRP for patients is a feasible procedure with encouraging local control rate and acceptable morbidity. This technique should be discussed as a treatment option for locally recurrent PCa in well-selected patients. 4.

Metabolic syndrome, dyslipidemia and prostate cancer recurrence after primary surgery or radiation in a veterans cohort.

Metabolic syndrome (MetS) has been hypothesized to be associated with cancer, including prostate cancer (PCa), but the relationship is not well characterized. We analyze the relationship between MetS features and localized PCa recurrence after treatment. Men having primary treatment for localized PCa were included from a multi-site regional veteran network. Recurrence was defined as nadir PSA +2 ng ml(-1) (radiation) or PSA⩾0.2 ng ml(-1) (prostatectomy). MetS was based on consensus professional society guidelines from the American Heart Association and International Diabetes Federation (three of: hypertension >130/85 mm Hg, fasting blood glucose ⩾100 mg dl(-1), waist circumference >102 cm, high-density lipoprotein <40 mg dl(-1), triglycerides ⩾150 mg dl(-1)). Closely related abnormality in low-density lipoprotein (LDL; >130 mg dl(-1)) was also examined. Analysis of PCa recurrence risk included multivariable Cox proportional hazards regression with propensity adjustment. Of the 1706 eligible men, 279 experienced recurrence over a median follow-up period of 41 months (range 1-120 months). Adjustment variables associated with PCa recurrence included: index PSA, Gleason, and tumor stage. Independent variables of interest associated with PCa recurrence were hyperglycemia and elevated LDL. Elevated LDL was associated with PCa recurrence (multivariable hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.03, 1.74; propensity adjusted HR 1.33, 95% CI 1.03, 1.72). There was also an association between impaired fasting glucose and PCa recurrence in (multivariable HR 1.54, 95% CI 1.10, 2.15; propensity adjusted HR 1.41, 95% CI 1.01, 1.95). MetS was not associated with PCa recurrence (multivariable: HR 0.96, 95% CI 0.61, 1.50; propensity adjusted HR 1.04, 95% CI 0.67, 1.62). PCa recurrence is not associated with MetS but is associated with elevated LDL and impaired fasting glucose. If confirmed, these data may help provide modifiable targets in preventing recurrence of PCa.

Long-term Health-related Quality of Life After Primary Treatment for Localized Prostate Cancer: Results from the CaPSURE Registry

BackgroundFew studies have reported on late declines and long-term health-related quality of life (HRQOL) after prostate cancer (PCa) treatment. ObjectiveWe assessed long-term HRQOL following various treatments for localized PCa. Design, setting, and participantsThis cohort study of HRQOL up to 10 yr after treatment used a prospectively accrued, nationwide PCa registry that collects longitudinal patient-reported HRQOL. InterventionVarious primary treatments for localized PCa. Outcome measurements and statistical analysisThe Medical Outcomes Studies 36-item Short Form and the University of California, Los Angeles, Prostate Cancer Index characterized physical function, mental health, and sexual, urinary, and bowel function and bother. Repeated measures mixed-model analysis assessed change in HRQOL by treatment over time, and logistic regression was used to measure the likelihood of a clinically significant decline in HRQOL. Results and limitationsAmong 3294 men, 1139 (34%) underwent nerve-sparing radical prostatectomy (NSRP), 860 (26%) underwent non-NSRP, 684 (21%) underwent brachytherapy, 386 (12%) underwent external beam radiotherapy, 161 (5%) underwent primary androgen deprivation therapy, and 64 (2%) pursued watchful waiting/active surveillance. Median follow-up was 74 mo (interquartile range: 50–102). Most treatments resulted in early declines in HRQOL, with some recovery over the next 1–2 yr and a plateau in scores thereafter. Surgery had the largest impact on sexual function and bother and on urinary function, radiation had the strongest effect on bowel function, and androgen deprivation therapy had the strongest effect on physical function. The main limitation was attrition among the cohort. ConclusionsAlthough most men experience initial declines in HRQOL in the first 2 yr after treatment, there is little change from 3 to 10 yr and most differences between treatments attenuated over time. Patient summaryVarious treatments for prostate cancer result in a distinct constellation of adverse effects on health-related quality of life, which may have a long-term impact. These findings are helpful regarding shared decision making over choice of primary treatment.

Results of a phase II trial of docetaxel (DOC), bevacizumab (BEV), and androgen deprivation therapy (ADT) for biochemical relapse (BCR) after definitive local therapy for prostate cancer (PC).

54 Background: Despite primary treatment for localized PC, 20-30% of men experience a BCR, detected by a rise in prostate-specific antigen (PSA). Though 30% of these patients develop metastatic disease, the optimal treatment of men with BCR has yet to be determined. In this trial, we evaluate the efficacy of DOC, BEV, and ADT for men with BCR after local therapy for PC. Methods: 41 men with a BCR and PSA doubling time of ≤10 months (mos) were enrolled. Patients received 4 cycles of DOC (75 mg/m2) every 3 weeks, 8 cycles of BEV (15 mg/kg) every 3 weeks, 18 mos of a luteinizing-hormone releasing hormone (LHRH) agonist, and 15 mos of bicalutamide (50 mg daily) beginning after completion of DOC. The primary endpoint was the proportion of patients free from PSA-progression 1 year after completion of ADT. Secondary endpoints included PSA response, testosterone recovery, and toxicity. Results: Median follow-up was 27.6 mos. Median age at diagnosis was 58 years. Median PSA at diagnosis was 6.7 ng/mL, with the majority of patients (59%) having Gleason 7 disease. Most patients underwent radical prostatectomy +/- radiation therapy (n=36). At baseline, 33 men (81%) had a normal testosterone (&gt; 240 ng/dL). The table describes the PSA responses for the entire cohort. 10 men (28%) had a normal testosterone 6 mos after completing ADT. 17 men (47%) had a normal testosterone 12 mos after completing ADT, of whom 5 (29%) had a PSA &lt;0.2 ng/mL at that time. There were 15% grade 1, 34% grade 2, 39% grade 3, and 12% grade 4 adverse events (AEs). The most frequent grade 3-4 AEs included neutropenia (24%), febrile neutropenia (11%), and hypertension (9%). Conclusions: DOC, BEV, and ADT for BCR resulted in complete responses in 16 men (44%) 1 year after completion of therapy. Longer follow-up is needed to determine the efficacy of this regimen. Clinical trial information: NCT00658697. [Table: see text]

1003 LONG TERM HEALTH RELATED QUALITY OF LIFE OUTCOMES AFTER PRIMARY TREATMENT FOR LOCALIZED PROSTATE CANCER: RESULTS FROM THE CAPSURE REGISTRY

Background: Few studies have reported on late declines and long-term health-related quality of life (HRQOL) after prostate cancer (PCa) treatment. Objective: We assessed long-term HRQOL following various treatments for localized PCa. Design, setting, and participants: This cohort study of HRQOL up to 10 yr after treatment used a prospectively accrued, nationwide PCa registry that collects longitudinal patientreported HRQOL. Intervention: Various primary treatments for localized PCa. Outcome measurements and statistical analysis: The Medical Outcomes Studies 36item Short Form and the University of California, Los Angeles, Prostate Cancer Index characterized physical function, mental health, and sexual, urinary, and bowel function and bother. Repeated measures mixed-model analysis assessed change in HRQOL by treatment over time, and logistic regression was used to measure the likelihood of a clinically significant decline in HRQOL. Results and limitations: Among 3294 men, 1139 (34%) underwent nerve-sparing radical prostatectomy (NSRP), 860 (26%) underwent non-NSRP, 684 (21%) underwent brachytherapy, 386 (12%) underwent external beam radiotherapy, 161 (5%) underwent primary androgen deprivation therapy, and 64 (2%) pursued watchful waiting/active surveillance. Median follow-up was 74 mo (interquartile range: 50–102). Most treatments resulted in early declines in HRQOL, with some recovery over the next 1–2 yr and a plateau in scores thereafter. Surgery had the largest impact on sexual function and bother and on urinary function, radiation had the strongest effect on bowel function, and androgen deprivation therapy had the strongest effect on physical function. The main limitation was attrition among the cohort. Conclusions: Although most men experience initial declines in HRQOL in the first 2 yr after treatment, there is little change from 3 to 10 yr and most differences between treatments attenuated over time. Patient summary: Various treatments for prostate cancer result in a distinct constellation of adverse effects on health-related quality of life, which may have a long-term impact. These findings are helpful regarding shared decision making over choice of primary treatment.

Nuclear Stat5a/b predicts early recurrence and prostate cancer–specific death in patients treated by radical prostatectomy

There is an urgent need for reliable markers to identify patients whose prostate cancer (PCa) will recur after initial therapy and progress to lethal disease. Gleason score (GS) is considered the most accurate predictive marker for disease-specific mortality after primary treatment of localized PCa. Most PCas cluster into groups of GS 6 and 7 with considerable variation in the disease recurrence and disease-specific death. In preclinical PCa models, Stat5a/b promotes PCa growth and progression. Stat5a/b is critical for PCa cell viability in vitro and for tumor growth in vivo and promotes metastatic dissemination of cancer in nude mice. Here, we analyzed the predictive value of high nuclear Stat5a/b protein levels in 2 cohorts of PCas: Material I (n = 562) PCas treated by radical prostatectomy (RP), and Material II (n = 106) PCas treated by deferred palliative therapy. In intermediate GS PCas treated by radical prostatectomy, high levels of nuclear Stat5a/b predicted both early recurrence (univariable analysis; P < .0001, multivariable analysis; HR = 1.82, P = .017) and early PCa-specific death (univariable analysis; P = .028). In addition, high nuclear Stat5a/b predicted early disease recurrence in both univariable (P < .0001) and multivariable (HR = 1.61; P = .012) analysis in the entire cohort of patients treated by RP regardless of the GS. Patients treated by deferred palliative therapy, elevated nuclear Stat5a/b expression was associated with early PCa-specific death by univariable Cox regression analysis (HR = 1.59; 95% CI = [1.04, 2.44]; P = .034). If confirmed in future prospective studies, nuclear Stat5a/b may become a useful independent predictive marker of recurrence of lethal PCa after RP for intermediate GS PCas.

Planning controlled clinical trials

Objective To address principles in the design and conduct of clinical trials on prostate cancer (PC) with special reference to localized disease. Methods In advance of and during the World Health Organization (WHO) conference on Prostate Cancer in Stockholm in September 1996, 6 members of a working group evaluated and reached consensus on key points for the planning and conduction of controlled clinical trials in PC. The key points discussed were 1) hypothesis formulation, 2) general methodological principles, 3) special problems of PC trials, 4) alternatives to randomization, and 5) trial organization. Results The hypothesis must be clearly formulated and also clinically relevant enough to justify the expenses (in a broad sense) of a randomized clinical trial. Patient selection, definition of endpoints, and sample size calculations must be carefully considered and correspond to the aims of the study. Stratification on important prognostic factors should be contemplated. Maintaining the accrual rate and ensuring compliance are critical for a quality study. Survival is the main endpoint and intention to treat analysis is the standard methodology. Secondary endpoints (eg, quality of life and costs) are important for the evaluation of many treatment modalities. The use of surrogate endpoints for survival, such as prostate-specific antigen (PSA) elevation, may be misleading. Surrogate endpoints require further validation. Special features, such as long natural history in localized disease and difficulties in assessing objective responses in advanced disease, need consideration in PC trials. The controlled randomized trial is the gold standard methodology. Nonrandomized trials are often hampered by severe methodological problems, such as selection bias and biased ascertainment of endpoints due to the doctor's or patient's preferences. For the organization of a successful trial, a wellconstructed study protocol is essential. Good clinical practice as defined within the European Community helps define and solve practical problems. Conclusions The past 30 years of poorly designed clinical research on PC has left us without reliable answers in key clinical issues regarding, for example, the efficacy of primary treatment of localized PC. It is a stimulating and important challenge to the urological scientific community to conduct well-organized controlled clinical trials.