Radical prostatectomy provides potentially curative removal of the cancer. However, it subjects patients to the morbidity and mortality of the surgery and may be neither necessary nor effective. Expectant management does not offer potential cure. However, it provides palliative therapy for symptomatic or metastatic disease progression, avoids potentially excessive and morbid interventions in asymptomatic patients, and emphasizes management approaches for focus on relieving symptoms while minimizing therapeutic complications.
The primary objective of this study is to determine which of two strategies is superior for the management of clinically localized CAP: 1) radical prostatectomy with early aggressive intervention for disease persistence or recurrence, 2) expectant management with reservation of therapy for palliative treatment of symptomatic or metastatic disease progression. Outcomes include total mortality, CAP mortality, disease free and progression free survival, morbidity, quality of life, and cost effectiveness.
Background: Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. Ninety percent of men with prostate cancer are over aged 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 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 due to the paucity of randomized controlled trials. The VA/NCI/AHRQ Cooperative Studies Program Study #407: Prostate cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy to watchful waiting in men with clinically localized prostate cancer. Methods: 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 versus watchful waiting conducted in Scandinavia. Results: We screened 13,022 men with prostate cancer at 52 United States 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 they were fully active. The median prostate specific antigen (PSA) was 7.8 ng/mL (mean 10.2 ng/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, approximately 43% had low risk, 36% had medium risk and 20% had high-risk prostate cancer. 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 U.S. and quite different from men in the Scandinavian trial. Conclusions: 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 to watchful waiting for men with predominately PSA detected 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.
BACKGROUND: L'efficacia della chirurgia contro osservazione per gli uomini con carcinoma prostatico localizzato rilevate mediante l'antigene prostatico specifico (PSA) non è noto.
METODI: Dal novembre 1994 al gennaio 2002 sono stati assegnati in modo casuale 731 uomini con carcinoma prostatico localizzato (età media, 67 anni; il valore del PSA mediana, 7,8 ng per millilitro) di prostatectomia radicale o di osservazione e li ha seguiti fino a gennaio del 2010. L'outcome primario era la mortalità; l'esito secondario era la mortalità prostata cancro.
RISULTATI: Durante il follow-up mediano di 10,0 anni, 171 dei 364 uomini (47,0%) assegnati alla prostatectomia radicale sono morti, rispetto ai 183 di 367 (49,9%) assegnato a osservazione (hazard ratio, 0.88; 95% intervallo di confidenza [ CI], 0,71-1,08; P = 0,22; riduzione del rischio assoluto, 2,9 punti percentuali). Tra gli uomini assegnati a prostatectomia radicale, 21 (5,8%) sono morti di cancro alla prostata o di trattamento, rispetto a 31 uomini (8,4%) assegnati alla sola osservazione (hazard ratio, 0.63; 95% CI, 0,36-1,09; P = 0,09; assoluta riduzione del rischio, 2,6 punti percentuali). L'effetto del trattamento su tutte le cause e mortalità cancro alla prostata non differiva in base all'età, alla razza, condizioni coesistenti, performance status auto-riferito, o caratteristiche istologiche del tumore. Prostatectomia radicale è stato associato a ridotta mortalità per tutte le cause tra gli uomini con un valore di PSA superiore a 10 ng per millilitro (P = 0.04 per interazione) e, eventualmente, tra quelli con tumori a rischio intermedio o alto rischio (p = 0.07 per interazione). Gli eventi avversi entro 30 giorni dopo l'intervento si è verificato in 21,4% degli uomini, tra cui un decesso.
In conclusione, tra gli uomini con carcinoma della prostata localizzato rilevato durante il primo periodo di test PSA, prostatectomia radicale non riducevano significativamente tutte le cause e mortalità prostata cancro, rispetto a osservazione, attraverso almeno 12 anni di follow-up. Differenze assolute erano meno di 3 punti percentuali. (Finanziato dal Department of Veterans Affairs Cooperative Studies Program e altri;. Numero PIVOT ClinicalTrials.gov, NCT00007644).
Radical prostatectomy provides potentially curative removal of the cancer. However, it subjects patients to the morbidity and mortality of the surgery and may be neither necessary nor effective. Expectant management does not offer potential cure. However, it provides palliative therapy for symptomatic or metastatic disease progression, avoids potentially excessive and morbid interventions in asymptomatic patients, and emphasizes management approaches for focus on relieving symptoms while minimizing therapeutic complications.
The primary objective of this study is to determine which of two strategies is superior for the management of clinically localized
CAP:
1) radical prostatectomy with early aggressive intervention for disease persistence or recurrence, 2) expectant management with reservation of therapy for palliative treatment of symptomatic or metastatic disease progression. Outcomes include total mortality, CAP mortality, disease free and progression free survival, morbidity, quality of life, and cost effectiveness.
