Prostate Cancer Intervention Versus Observation Trial Research Articles

Re: Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-Up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT).

No AccessJournal of UrologyUrological Survey1 Jul 2020Re: Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-Up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT) Samir S. TanejaMD Samir S. TanejaSamir S. Taneja More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001056.01AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-Up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT)." The Journal of Urology, 204(1), p. 186 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 204Issue 1July 2020Page: 186-186 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Samir S. Taneja More articles by this author Expand All Advertisement PDF downloadLoading ...

Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT)

BackgroundVery long-term mortality in men with early prostate cancer treated with surgery versus observation is uncertain. ObjectiveTo determine long-term effects of surgery versus observation on all-cause mortality for men with early prostate cancer. Design, setting, and participantsThis study evaluated long-term follow-up of a randomized trial conducted at the US Department of Veterans Affairs and National Cancer Institute sites. The participants were men (n=731) ≤75yr of age with localized prostate cancer, prostate-specific antigen (PSA) <50ng/ml, life expectancy ≥10yr, and medically fit for surgery. InterventionRadical prostatectomy versus observation. Outcome measurements and statistical analysisAll-cause mortality was assessed in the entire cohort and patient and tumor subgroups. Intention-to-treat analysis was conducted using Kaplan-Meier methods with log-rank tests and Cox proportional hazard models; cumulative mortality incidence, between-group differences, and relative risks were also assessed at predefined time periods. Results and limitationsDuring 22.1yr (median follow-up for survivors=18.6yr; interquartile range: 16.6–20.0), 515 men died; 246 of 346 men (68%) were assigned to surgery versus 269 of 367 (73%) assigned to observation (hazard ratio 0.84 [95% confidence interval {CI}: 0.70–1.00]; p= 0.044 [absolute risk reduction = 5.7 percentage points, 95% CI: –0.89 to 12%]; relative risk: 0.92 [95% CI: 0.84–1.01]). The restricted mean survival in the surgical group was 13.6 yr (95% CI: 12.9–14.3) versus 12.6 yr (95% CI: 11.8–13.3) in the observation group; a mean of 1 life-year was gained with surgery. Results did not significantly vary by patient or tumor characteristics, although differences were larger favoring surgery among men aged <65 yr, of white race, and having better health status, fewer comorbidities, ≥34% positive prostate biopsy cores, and intermediate-risk disease. Results were not adjusted for multiple comparisons, and we could not assess outcomes other than all-cause mortality. ConclusionsSurgery was associated with small very long-term reductions in all-cause mortality and increases in years of life gained. Absolute effects did not vary markedly by patient characteristics. Absolute effects and mean survival were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. Patient summaryIn this randomized study, we evaluated death from any cause in men with early prostate cancer treated with either surgery or observation. Overall, surgery may provide small very long-term reductions in death from any cause and increases in years of life gained. Absolute effects were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. Strategies are needed to identify men needing and benefitting from surgery while reducing ineffective treatment and overtreatment.

MP05-05 ASSESSING THE EXTERNAL VALIDITY OF THE UPDATED PROSTATE CANCER(PCA) INTERVENTION VERSUS OBSERVATION TRIAL (PIVOT)

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy I1 Apr 2018MP05-05 ASSESSING THE EXTERNAL VALIDITY OF THE UPDATED PROSTATE CANCER(PCA) INTERVENTION VERSUS OBSERVATION TRIAL (PIVOT) Firas Abdollah, Deepansh Dalela, Akshay Sood, Jacob Keeley, Nicolas von Landenberg, Quoc-Dien Trinh, Shaheen Alanee, James O Peabody, Craig G Rogers, and Mani Menon Firas AbdollahFiras Abdollah More articles by this author , Deepansh DalelaDeepansh Dalela More articles by this author , Akshay SoodAkshay Sood More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Nicolas von LandenbergNicolas von Landenberg More articles by this author , Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author , Shaheen AlaneeShaheen Alanee More articles by this author , James O PeabodyJames O Peabody More articles by this author , Craig G RogersCraig G Rogers More articles by this author , and Mani MenonMani Menon More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.176AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The PIVOT study has been instrumental in shaping health policy and public discourse about treatment of PCa in the US. However, concerns have been raised about the external validity of this trial to men diagnosed with PCa in the US. We assessed the study generalizability (external validity) to men who were diagnosed with PCa using three nationally representative databases. METHODS We used data of men diagnosed with PCa within the Surveillance, Epidemiology, and End-Results (SEER; population based registry) 2000-2004, National Cancer Database (NCDB; hospital based registry) 2004-2005, and Prostate, Lung, Colorectal and Ovarian (PLCO) trial between 1993-2001. We included only men undergoing surgery or observation who satisfied the inclusion criteria of PIVOT. Within SEER, men were excluded from the comparative analyses if surgery was not recommended (because of pre-existing conditions or otherwise): these men were separately assessed for age at diagnosis and overall mortality. Chi-square test and ANOVA test were used to compare proportions and means, respectively. RESULTS A total of 2847, 60089, and 63303 PCa patients were included from PLCO, SEER, and NCDB respectively. Mean age (standard deviation) at diagnosis of clinically localized PCa for men in PIVOT was 67.0 (5.2) years, compared to 65.8 (4.5), 61.3 (7.3) and 60.2 (7.0) in PLCO, SEER and NCDB respectively (p<.001). The majority of men (94-96.4%) in PLCO and NCDB had Charlson comorbidity index (CCI) of 0, compared to only 56% for men in PIVOT (p<.001). No comorbidity data were available in SEER. Overall mortality was 64% in PIVOT (over a median 12.7-year follow-up) vs. 8-23% in the three examined cohorts (the latter over a median 12.3-year follow-up). Interestingly, within SEER, the mean age at diagnosis for men who were not recommended surgery was 65.1 years, with overall mortality 50% over a median follow-up of 12.5 years. CONCLUSIONS These findings across multiple large datasets consistently demonstrate that men within PIVOT were older and sicker than their counterparts across the US. Interestingly, the reported overall survival in PIVOT was worse even when compared to men within SEER who were not recommended definitive treatment. These findings suggest a sampling bias, and highlight the lack of generalizability, and thus external validity, of PIVOT findings to men diagnosed with clinically localized PCa in the US. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e43-e44 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Firas Abdollah More articles by this author Deepansh Dalela More articles by this author Akshay Sood More articles by this author Jacob Keeley More articles by this author Nicolas von Landenberg More articles by this author Quoc-Dien Trinh More articles by this author Shaheen Alanee More articles by this author James O Peabody More articles by this author Craig G Rogers More articles by this author Mani Menon More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

FR-22 FROM "END OF UROLOGY" TO ENDOUROLOGY: UROLOGIC LEGACY OF THE THE MINNEAPOLIS VA

You have accessJournal of UrologyHistory Forum1 Apr 2018FR-22 FROM "END OF UROLOGY" TO ENDOUROLOGY: UROLOGIC LEGACY OF THE THE MINNEAPOLIS VA Giulia Lane, Maria Uloko, Vikram Narayan, and Cesar Ercole Giulia LaneGiulia Lane More articles by this author , Maria UlokoMaria Uloko More articles by this author , Vikram NarayanVikram Narayan More articles by this author , and Cesar ErcoleCesar Ercole More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.3042AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The Minneapolis VA Section of Urology has contributed to Urologic research and trained leaders in Urology since its affiliation with the University of Minnesota in 1946. It is the birthplace to the Gleason score, the Fuhrman grading system and Endourology. Herein we recount the Urologic contributions of the Minneapolis VAMC. METHODS A review of Urologic literature from the Minneapolis VAMC from 1946 to present. RESULTS Researchers at the Minneapolis VAMC helped shaped early innovations in Urologic Oncology. The VA Cooperative Urologic Research Group (VACURG) was developed by Dr. George Mellinger, Chief of Urology, in 1959. Dr. Mellinger enlisted Dr. Donald Gleason's aid in the development of a grading system for prostate cancer for the VACURG. Dr. Gleason's Grading system, first presented in 1965, has become the sole recommended grading system for prostate cancer. In the realm of renal tumors, Dr. Susan Fuhrman devised the Fuhrman Grading system in 1982 at the Minneapolis VAMC pathology department. The Fuhrman grading system gained popularity and has been found to be a prognostic factor for renal carcinoma. Dr. Paul Lange (VAMC Urology Chief 1977-86) alongside Dr. Thomas Hakala and Dr. Elwin Fraley (Chairman of Urology at the University of Minnesota 1969-93), studied the tumor markers for testicular cancer at the Minneapolis VAMC, providing evidence for the benefit of their clinical use.Dr. Fraley trained and recruited the Urologists that created the field of Endourology. In 1978, Dr. Arthur Smith and Dr. Lange published the first account of antegrade ureteral stent placement through a percutaneous nephrostomy tract, which was performed at the Minneapolis VAMC. Dr. Fraley coined the term Endo-Urology in 1979 and helped popularize the techniques through training courses in Minneapolis. Today, the Minneapolis VAMC is a lead institution for evidence based Urology through the work of Dr. Timothy Wilt and Dr. Philip Dahm. Dr. Wilt served as lead investigator in the the Prostate Cancer Intervention versus Observation Trial (PIVOT) and member of the United States Preventative Task Force (USPSTF) on prostate specific antigen. Dr. Dahm currenlty leads the the Cochrane Urology Collaborative Review Group from the Minneapolis VAMC. The VAMC also serves as a lead institution U.S. Grading Recommendations Assessment, Develop and Evaluation (GRADE) network. CONCLUSIONS The Minneapolis VA Section of Urology has produced leaders in Urology who contributed to the field of Urologic Oncology, founded the field of Endourology and continue to promote evidence based Urology. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1249 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Giulia Lane More articles by this author Maria Uloko More articles by this author Vikram Narayan More articles by this author Cesar Ercole More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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In the Prostate Cancer Intervention Versus Observation Trial (PIVOT), surgery was not associated with lower mortality compared with observation. However, the high competing mortality rate of approximately 33% after 10 yr among the PIVOT study population has raised concerns on the generalizability of these results. We investigated 4282 patients who underwent radical prostatectomy at our institution between 1992 and 2010 to determine which subgroups harbored a competing (non-prostate cancer) mortality risk comparable to that of PIVOT and tested several combinations of higher age and comorbidities (“worst case scenarios”) to identify subgroups reaching or even superseding the competing mortality rate of the PIVOT population. The competing mortality rate of PIVOT was not reached till an age-adjusted Charlson score of 5 or higher (corresponding to an age of 70–79 yr with diabetes with end-organ damage). Only 8.9% of patients belonged to this high-risk subgroup, and only small subgroups comprising 1–5% patients superseded the competing mortality rate among the PIVOT study population. This data underline that the results of PIVOT should be used with great caution to exclude candidates for radical prostatectomy with comorbidities from curative treatment. Patient summaryOnly <10% of patients selected for radical prostatectomy reached the competing mortality rate of approximately 33% observed in the Prostate Cancer Intervention Versus Observation Trial (PIVOT). The results of PIVOT should be used with great caution to exclude patients with concomitant diseases who seem otherwise fit for radical prostatectomy from curative treatment.

PNFLBA-11 RADICAL PROSTATECTOMY VERSUS OBSERVATION FOR EARLY PROSTATE CANCER: FOLLOW-UP RESULTS OF THE PROSTATE CANCER INTERVENTION VERSUS OBSERVATION TRIAL (PIVOT)

You have accessJournal of UrologyPlenary: Next Frontier (PNFLBA)1 Apr 2017PNFLBA-11 RADICAL PROSTATECTOMY VERSUS OBSERVATION FOR EARLY PROSTATE CANCER: FOLLOW-UP RESULTS OF THE PROSTATE CANCER INTERVENTION VERSUS OBSERVATION TRIAL (PIVOT) Timothy Wilt, Karen Jones, Michael Barry, Gerald Andriole, Daniel Culkin, Thomas Wheeler, William Aronson, and Michael Brawer Timothy WiltTimothy Wilt More articles by this author , Karen JonesKaren Jones More articles by this author , Michael BarryMichael Barry More articles by this author , Gerald AndrioleGerald Andriole More articles by this author , Daniel CulkinDaniel Culkin More articles by this author , Thomas WheelerThomas Wheeler More articles by this author , William AronsonWilliam Aronson More articles by this author , and Michael BrawerMichael Brawer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.03.037AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We previously found no mortality differences between surgery and observation in men with localized prostate cancer through 12 years. Uncertainty persists regarding nonfatal health outcomes and long-term mortality. We evaluated clinically important outcomes for men with early stage prostate cancer diagnosed during the early PSA era who were randomly assigned to treatment with either surgery or observation. METHODS Between 1994 and 2002, we randomly assigned 731 men with localized prostate cancer to radical prostatectomy or observation. We extended follow-up through August 2014 for our primary outcome, all-cause mortality, and main secondary outcome, prostate cancer mortality. We describe disease progression, additional treatments received and patient reported outcomes through the original follow-up of January 2010. RESULTS During 19.5 years of follow-up (Median=12.7 years), 223 of 364 men (61.3%) assigned to surgery died compared to 245 of 367 (66.8%) assigned to observation; (Absolute risk reduction(ARR)=5.5%, 95% Confidence Interval[CI], -1.5, 12.4); Hazard ratio(HR)=0.84, 95%CI, 0.70, 1.01; P=0.06). Prostate cancer mortality occurred in 27 men (7.4%) randomized to surgery versus 42 men (11.4%) randomized to observation; (ARR = 4.0, 95%CI, -0.2 to 8.3; HR=0.63, 95% CI, 0.39 to 1.02; P=0.06). The effect of surgery on mortality did not vary by baseline patient characteristics. Radical prostatectomy may have reduced all-cause mortality among men with intermediate (ARR=14.5%, 95%CI, 2.8 to 25.6) but not low (ARR=0.6%, 95%CI, -10.5 to 11.8) or high risk disease (ARR=2.3%, 95%CI, -11.5 to 16.1)(P for interaction = 0.08). Surgery reduced disease progression treatment, primarily androgen deprivation for asymptomatic, local or PSA progression, by 26.2 percentage points(95%CI, 19.0 to 32.9). Urinary incontinence, erectile and sexual dysfunction were each greater by more than 30 percentage points with surgery. Disease or treatment related bother and limitations in activities of day-to-day living were greater with surgery though 2 years but not at later follow-up. CONCLUSIONS After nearly 20 years, surgery did not significantly reduce all-cause or prostate cancer mortality compared with observation. Surgery had more adverse effects, but reduced disease progression and subsequent treatments; most asymptomatic, local or biochemical and may have reduced all-cause mortality in men with intermediate risk disease. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e915 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Timothy Wilt More articles by this author Karen Jones More articles by this author Michael Barry More articles by this author Gerald Andriole More articles by this author Daniel Culkin More articles by this author Thomas Wheeler More articles by this author William Aronson More articles by this author Michael Brawer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Generalizability of the Prostate Cancer Intervention Versus Observation Trial (PIVOT) Results to Contemporary North American Men with Prostate Cancer

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) concluded that radical prostatectomy (RP) offered no survival benefit compared with observation in men with clinically localized prostate cancer (PCa). We identified patients within the National Cancer Database (NCDB) for the period 2004-2012 who met the inclusion criteria of PIVOT (ie, histologically confirmed PCa, clinical stage T1–2NxM0, prostate-specific antigen <50 ng/ml, age <75 yr, estimated life expectancy >10 yr, and undergoing RP or observation as initial treatment within 12 mo of diagnosis) to confirm the generalizability of the PIVOT results to the US population. Life expectancy was calculated using the US Social Security Administration life tables and was adjusted for comorbidities at diagnosis. Compared with PIVOT, men in the NCDB were younger (mean age 60.3 vs 67.0 yr) and healthier (Charlson-Deyo comorbidity index of 0: 93% vs 56%; both p < 0.001). Furthermore, 42% of men randomized to receive RP in PIVOT harbored D’Amico low-risk PCa, whereas 32% of men undergoing RP in the NCDB had low-risk disease. Our findings were confirmed in a sensitivity analysis including men regardless of life expectancy but satisfying all other inclusion criteria of PIVOT. Given that the NCDB represents nearly 70% of all incident cancers diagnosed in the United States, our data provide further evidence that PIVOT results may not be generalizable to contemporary clinical practice. Patient summaryWe observed that men diagnosed with clinically localized prostate cancer within the National Cancer Database (2004–2012) were younger, healthier, and more likely to have radical prostatectomy for higher risk disease than men in the Prostate Cancer Intervention Versus Observation Trial (PIVOT), raising questions about the applicability of PIVOT conclusions to the contemporary US population.

PD37-02 SURVIVAL OUTCOMES AFTER PROSTATECTOMY IN A HEALTHY POPULATION OF VETERANS: COMPARISON TO THE SURGICAL COHORT FROM PIVOT

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV1 Apr 2016PD37-02 SURVIVAL OUTCOMES AFTER PROSTATECTOMY IN A HEALTHY POPULATION OF VETERANS: COMPARISON TO THE SURGICAL COHORT FROM PIVOT Eric Kim, Suhong Luo, Katiuscia O'Brian, Niraj Badhiwala, Bettina Drake, Kenneth Carson, M'Liss Hudson, and Robert Grubb Eric KimEric Kim More articles by this author , Suhong LuoSuhong Luo More articles by this author , Katiuscia O'BrianKatiuscia O'Brian More articles by this author , Niraj BadhiwalaNiraj Badhiwala More articles by this author , Bettina DrakeBettina Drake More articles by this author , Kenneth CarsonKenneth Carson More articles by this author , M'Liss HudsonM'Liss Hudson More articles by this author , and Robert GrubbRobert Grubb More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1141AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent controversy regarding prostate-specific antigen (PSA) screening is based in part on the results of the Prostate Cancer Intervention versus Observation Trial (PIVOT). Although radical prostatectomy (RP) remains the gold-standard for curative treatment for localized prostate cancer (PCa), the study suggests there is no survival benefit for surgery compared to watchful waiting. We examined survival outcomes after RP for a healthy population of veterans and compared this to the RP cohort from PIVOT. METHODS We utilized a national cohort of 231,174 veterans between the ages of 40 and 70 years, free of heart disease, who at least annually visited the Veterans Healthcare Administration (VHA), who underwent PSA screening between October 2000 and September 2007. We identified 2805 veterans who were diagnosed with PCa, 966 of these veterans underwent RP. Kaplan-Meier and Cox proportional hazards analyses were performed for overall (OS) and cancer-specific survival (CSS). Comorbidity was measured by Charlson Comorbidity Index. Chi-squared test was used to compare our study cohort and PIVOT. P-values less than 0.05 were considered significant. RESULTS At a median follow-up of 93 months, 75 of the 966 (7.8%) men in our study cohort died as compared to 171 of the 364 (47.0%) men in the RP arm of PIVOT at median follow-up of 120 months (p<0.0001). In our study cohort, 12 deaths were attributable to PCa (1.2%), whereas 21 of the 364 (5.8%) men in the RP arm of PIVOT died of PCa (p<0.0001). Patients in our study cohort were more likely to have Gleason >7 PCa than in the surgery arm of PIVOT (50.0% versus 26.9%, p<0.0001). No patients in our study cohort carried a diagnosis of heart disease at study entry, while 11% of men in the surgery arm of PIVOT had a history of myocardial infarction or congestive heart failure and 9.9% had a history of peripheral vascular disease, cerebral vascular disease, or stroke. CONCLUSIONS Although with shorter median follow-up, OS and CSS were significantly higher for patients undergoing RP in our study cohort than the RP arm of PIVOT. Differences in OS between the two cohorts may be attributable to differences in baseline cardiovascular health. Additional studies are needed to determine if RP provides a survival benefit over watchful waiting in veterans with less comorbidity. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e855 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Eric Kim More articles by this author Suhong Luo More articles by this author Katiuscia O'Brian More articles by this author Niraj Badhiwala More articles by this author Bettina Drake More articles by this author Kenneth Carson More articles by this author M'Liss Hudson More articles by this author Robert Grubb More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Comorbidity and the Receipt of Curative Therapy for Favorable-risk Prostate Cancer Prior to and Following the Publication of PIVOT

The publication of the randomized Prostate Cancer Intervention Versus Observation Trial (PIVOT) in July 2012, in which men with favorable-risk prostate cancer (PCa) were not found to benefit from radical prostatectomy, had the potential to shift PCa practice patterns. Using a prospectively assembled database of 5398 men with low-risk or favorable intermediate-risk PCa selected for curative treatment with brachytherapy in the years preceding and the year following the publication of PIVOT, we evaluated the odds of receiving curative treatment after adjusting for risk group (favorable intermediate vs low), race (black, Hispanic, or other), number of cardiometabolic comorbidities, and age. Following publication, the receipt of curative treatment was significantly lower (adjusted odds ratio [AOR]: 0.40; 95% confidence interval [CI], 0.16–0.99; p=0.05) among men with at least two cardiometabolic comorbidities, in contrast to the increasing trend (p=0.02) noted prior to PIVOT. Among black men, a subgroup at risk for occult high-grade disease, the odds of receiving curative treatment increased after PIVOT (AOR: 1.55; 95% CI, 1.06–2.26; p=0.02). These observations suggest that PIVOT's publication appropriately contributed to decreasing the use of curative treatment in men unlikely to benefit. Patient summaryThe Prostate Intervention Versus Observation Trial (PIVOT) showed that radical prostatectomy did not benefit men with favorable-risk prostate cancer. Following the publication of PIVOT, the selection of men with multiple medical issues for curative treatment declined, whereas treatment of men at high risk of having aggressive prostate cancer increased.

Comorbidity and the receipt of curative therapy for favorable-risk prostate cancer prior to and following the publication of PIVOT.

17 Background: On July 19, 2012, the Prostate Cancer Intervention versus Observation Trial (PIVOT) was published and reported that after a median follow up of 10 years, radical prostatectomy neither improved overall survival nor reduced prostate cancer (PC)-specific mortality in men with low-risk PC compared to watchful waiting. However, the trial’s applicability may be somewhat limited by the participants’ poorer-than-average overall health. This study aimed to evaluate the impact of the PIVOT by assessing practice patterns before and after its publication. Methods: Between October 1997 and May 2013, 6,818 men with low-risk (n = 5,081, 74.5%) or favorable intermediate-risk (N = 1,737, 25.5%) PC were treated with curative intent at the Chicago PC Foundation. We compared the proportions of these men with ≥2, 1, or 0 comorbid conditions, restricted to myocardial infarction, congestive heart failure, diabetes mellitus, and coronary artery disease. We assessed for a trend in these proportions by time tertile prior to the PIVOT’s publication and compared them one month following PIVOT to the final pre-publication time tertile. Results: Of 6,818 men treated with curative intent, 5,208 (76.5%), 1,307 (19.2%), and 293 (4.3%) had 0, 1, and ≥2 comorbidities, respectively. Prior to PIVOT, the proportion of men with the greatest comorbidity (≥2) increased by time tertile (3.5% vs. 4.2% vs. 5.4%; p = 0.002), while 1 month following publication, there was a decline in the proportion of men with the highest degree of comorbidity (5.4% vs. 2.9%; p = 0.05). In addition to the drop in men with greatest comorbidity, men treated following the publication of the PIVOT were also younger (median age 65.7 vs. 66.8 years; p = 0.04), more likely to be black or Hispanic (24.7% vs. 17.4%; p = 0.003), and more likely to have favorable intermediate than low-risk PC (36.1% vs. 28.4%; p = 0.007). Conclusions: Following the publication of the PIVOT, men with low or favorable intermediate-risk PC whose health was poorer than the national average were less likely to undergo curative treatment, whereas men at higher risk for harboring occult high grade PC despite favorable-risk indices were more likely to undergo curative treatment.

Prostate-specific antigen-based screening: controversy and guidelines.

Although prostate-specific antigen (PSA) screening has improved the detection of prostate cancer, allowing for stage migration to less advanced disease, the precise mortality benefit of early detection is unclear. This is in part due to a discrepancy between the two large randomized controlled trials comparing PSA screening to usual care. The European Randomized Study of Screening for Prostate Cancer (ERSPC) found a survival benefit to screening, while the United States Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial did not. Furthermore, the benefit of immediate surgical intervention for screen-detected prostate cancer is unclear, as the results superficially differ between the two large randomized controlled trials comparing prostatectomy to observation. The Prostate Cancer Intervention Versus Observation Trial (PIVOT) found no survival benefit for prostatectomy in PSA screened U.S. men, while the Scandinavian Prostate Cancer Group Study Number Four (SPCG-4) found a survival benefit for prostatectomy in clinically diagnosed prostate cancer. As a result of the controversy surrounding PSA screening and subsequent prostate cancer treatment, guidelines vary widely by organization.

Management of localized prostate cancer: the pendulum swings (back to the middle).

Herein, we discuss 18-year follow-up data from the Scandinavian Prostate Cancer Group-4 (SPCG-4) trial, a randomized study comparing observation and radical prostatectomy (RP) in patients with localized prostate cancer. The results of this study are contrasted with another study employing a similar randomization, the Prostate Cancer Intervention Versus Observation Trial (PIVOT). We highlight several key differences in study eligibility and enrollment that may account for distinct results, and describe how these datasets impact the complex landscape of therapy for localized prostate cancer.

The 6-item CAPRA-S score predicted cancer recurrence after radical prostatectomy

Source Citation Punnen S, Freedland SJ, Presti JC Jr, et al. Multi-institutional validation of the CAPRA-S score to predict disease recurrence and mortality after radical prostatectomy. Eur Urol. 2013;S0302-2838:00352-7. 23587869

Ascertaining cause of death among men in the Prostate Cancer Intervention Versus Observation Trial

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) randomized 731 men with localized prostate cancer to radical prostatectomy or observation. We describe the methods and results for cause-of-death assignments in PIVOT, and compare them to alternative strategies for ascertaining prostate cancer-specific mortality, as well as to the methods and results in the similar Scandinavian Prostate Cancer Group Study 4 (SPCG-4) trial. Three PIVOT Endpoints Committee members, blinded to randomized treatment assignments, reviewed medical records and death certificates when available to assign a cause of death using a primary and a secondary adjudication question. Initial disagreements were resolved through discussion. The level of initial agreement among committee members was examined, as well as guesses at randomized treatment assignments for a convenience sample of cases. Final cause of death determinations were compared to death certificates. Complete agreement on cause of death by all three committee members before any discussion was achieved in 200/354 (56%) cases on the primary and 209/354 (59%) cases on the secondary. However, complete agreement on the primary rose to 306/354 (86%) when 'definite' and 'probably' categories were collapsed, as planned a priori. The three committee members' proportions of correct guesses of randomized treatment assignment were 82/121 (68%), 113/148 (76%), and 99/134 (74%). Using the committee's final adjudications as a gold standard, death certificates had suboptimal sensitivities, specificities, or predictive values depending on how they were used to determine cause of death. There was no separate 'gold standard' by which to judge the accuracy of the final endpoints committee adjudications, and useful death certificates could not be obtained on about a third of PIVOT participants who died. The low level of initial agreement on cause of death among endpoint committee members and the potential for biased determinations due to partial unblinding to treatment assignment raise methodologic concerns about using prostate cancer mortality as an endpoint in clinical trials like PIVOT.

There is no role for focal therapy in prostate cancer

There is no role for focal therapy in prostate cancer

Screening and efficacy of radical prostatectomy

Screening and efficacy of radical prostatectomy

Effects of Screening on Radical Prostatectomy Efficacy: The Prostate Cancer Intervention Versus Observation Trial

The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial showed that radical prostatectomy (RP) reduced prostate cancer deaths with an absolute mortality difference (AMD) between the RP and watchful waiting arms of 6.1% (95% confidence interval [CI] = 0.2% to 12.0%) after 15 years. In the United States, the Prostate Cancer Intervention Versus Observation Trial (PIVOT) produced an AMD of 3% (95% CI = -1.1% to 6.5%) after 12 years. It is not known whether a higher frequency of screen detection in PIVOT explains the lower AMD. We assumed the SPCG-4 trial represents RP efficacy and prostate cancer survival in an unscreened population. Given the fraction of screen-detected prostate cancers in PIVOT, we adjusted prostate cancer survival using published estimates of overdiagnosis and lead time to project the effect of screen detection on disease-specific deaths. On the basis of published estimates, we assumed that 32% of screen-detected cancers were overdiagnosed and a mean lead time among non-overdiagnosed cancers of 7.7 years. When we adjusted prostate cancer survival for the 76% of case patients in PIVOT who were screen detected, we projected that the AMD after 12 years would be 2.0% (95% CI = -1.6% to 5.6%) based on variation in published estimates of overdiagnosis and mean lead time in the United States. If RP efficacy and prostate cancer survival in the absence of screening are similar to that in the SPCG-4 trial, then overdiagnosis and lead time largely explain the lower AMD in PIVOT. If these artifacts of screening are the correct explanation, then there is a subset of case subjects that should not be treated with RP, and identifying this subset should lead to a clearer understanding of the benefit of RP in the remaining cases.

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) in Perspective

Low risk localised prostate cancer may be able to be observed rather than treated according to the Prostate Cancer Intervention Versus Observation Trial (PIVOT). This review summarises the key issues surrounding the debate in the management of localised prostate cancer, and contextualises the PIVOT’s contribution.

The Prostate Cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): Design and Baseline Results of a Randomized Controlled Trial Comparing Radical Prostatectomy With Watchful Waiting for Men With Clinically Localized Prostate Cancer

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. In the United States, 90% of men with prostate cancer are more than age 60 years, diagnosed by early detection with the prostate-specific antigen (PSA) blood test, and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting (WW), surgery to remove the prostate gland (radical prostatectomy), external-beam radiation therapy and interstitial radiation therapy (brachytherapy), and androgen deprivation. Little is known about the relative effectiveness and harms of treatments because of the paucity of randomized controlled trials. The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study #407:Prostate Cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy with WW in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods, and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy vs WW conducted in Scandinavia. We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment. From these, 5023 met initial age, comorbidity, and disease eligibility criteria, and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African American. Approximately 85% reported that they were fully active. The median PSA was 7.8ng/mL (mean 10.2ng/mL). In three-fourths of men, the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade, and tumor stage, it was found that approximately 40% had low-risk, 34% had medium-risk, and 21% had high-risk prostate cancer based on local histopathology. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinically localized prostate cancer.

Surgery no better than observation for localized prostate cancer

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) found that men with localized prostate cancer survived just as long regardless of whether they underwent prostate-removal surgery. The study enrolled 731 men with localized prostate cancer diagnosed through prostate-specific antigen (PSA) blood tests and biopsies.1 Approximately one-half of the men were randomly assigned to undergo radical prostatectomies whereas the others were assigned to an observation group. The latter received palliative care or chemotherapy if their cancer progressed. After 12 years of follow-up, researchers found no real difference between the groups in terms of the number of men who died of prostate cancer or its treatment. Participants were classified as having low-risk, intermediate-risk, or high-risk prostate cancer based on their PSA levels and Gleason scores. They found that men in the low-risk category were least likely to benefit from surgery, and the results support the recommendation that men with localized prostate cancer, and particularly those with low-risk disease, benefit from observation versus surgery. Approximately 21.4% of men in the surgery group developed a complication within 30 days of surgery, including 1 death. Infection was the most common complication, whereas urinary incontinence and impotence were much more common 2 years after surgery in the surgery group compared with the observation group. In an accompanying editorial, Ian Thompson, MD, of the University of Texas Health Science Center in San Antonio, and Catherine Tangen, DrPH, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, pointed out that the trial's size may have impacted its results. They noted that PIVOT originally was designed to enroll 2000 patients, but because of difficulty in recruiting patients, the trial was changed. Ultimately, they concluded that there were too few patients to definitively demonstrate that surgery could reduce mortality. Meanwhile, the American Society of Clinical Oncology published recommendations by an expert committee that advised against PSA screening for prostate cancer in men with a life expectancy of fewer than 10 years and recommended that physicians discuss the potential benefits and risks of PSA testing with men who have a life expectancy of 10 years or more.2 These recommendations are similar to those of the American Cancer Society, which suggests that this discussion should occur starting at age 50 years for men who are at average risk of developing prostate cancer and at age 45 years for men who are at higher risk of the disease. Reference