Clinical trial NCT00007644: Prostate Cancer Intervention Versus Observation Trial (PIVOT)
Official title: CSP #407 - Prostate Cancer Intervention Versus Observation Trial (PIVOT): A Randomized Trial Comparing Radical Prostatectomy Versus Palliative Expectant Management for the Treatment of Clinically Localized Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: cancer of the prostate (CAP)
cancer treatment
chronic diseases
expectant management
genitourinary
prostate
prostate specific cancer mortality
radical prostatectomy
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Agency for Healthcare Research and Quality (AHRQ)
name: National Cancer Institute (NCI)
First posted: 2001-01-01
Enrollment: 731
Sex: MALE
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Primary Hypothesis: To determine whether radical prostatectomy or expectant management is more effective in reducing mortality and extending life.

Secondary Hypothesis: To determine which treatment strategy is superior in terms of prostate specific cancer mortality, quality of life, occurrence or recurrence of symptoms and need for cancer treatment.

Intervention: 1) Radical prostatectomy, plus intervention for evidence of disease persistence or recurrence, 2) Expectant management with palliative therapy reserved for symptomatic or metastatic disease progression.

Primary Outcomes: All cause mortality.

Study Abstract: Cancer of the prostate (CAP) is the most common nondermatologic and the second most frequent cause of cancer deaths in men. No cure is currently possible for disseminated disease. Cancer confined to the prostate is believed to be curable, with the most frequently recommended therapy being surgical extirpation of the tumor with radical prostatectomy. However, despite increasing cancer detection and aggressive surgical treatment, population-based mortality rates from prostate cancer have not decreased, neither nationally nor in states with high rates of radical prostatectomy. Existing evidence does not demonstrate the superiority of this procedure compared to expectant management in the treatment of localized prostate cancer. Data from case series suggest that either treatment approach provides equivalent all-cause as well as prostate cancer specific mortality. The only randomized trial was limited by a small sample size but the results favored expectant management.

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.

Eligibility criteria: Inclusion Criteria:

* Patients with clinically localized CAP
* Diagnosis of Prostate Cancer within previous 6 months
* Age 75 years or younger

Exclusion Criteria:

PSA \> 50 ng/ml Bone scan consistent with metastatic disease Other evidence that cancer of the prostate is not clinically localized Diagnosis of prostate cancer greater than 12 months ago Life expectancy less than 10 years Serum creatinine greater than 3 mg/dl Myocardial infarction within last 6 months Unstable angina New York Heart Association Class III or IV congestive heart failure Severe pulmonary disease Lifer failure Severe dementia Debilitating illness Malignancies, except for nonmelanomatous skin cancer, in the last 5 years

Primary outcomes:
measure: All Cause Mortality
timeFrame: From date of randomization until date of death from any cause, assessed until end of study, up to 16 years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: VA Medical Center, Birmingham
state: Alabama
city: North Little Rock
country: United States
facility: Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
state: Arkansas
city: Long Beach
country: United States
facility: VA Medical Center, Long Beach
state: California
city: San Francisco
country: United States
facility: VA Medical Center, San Francisco
state: California
city: Sepulveda
country: United States
facility: VA Greater Los Angeles HCS, Sepulveda
state: California
city: Tampa
country: United States
facility: James A. Haley Veterans Hospital, Tampa
state: Florida
city: Boise
country: United States
facility: VA Medical Center, Boise
state: Idaho
city: Chicago
country: United States
facility: Jesse Brown VAMC (WestSide Division)
state: Illinois
city: Indianapolis
country: United States
facility: Richard Roudebush VA Medical Center, Indianapolis
state: Indiana
city: Iowa City
country: United States
facility: VA Medical Center, Iowa City
state: Iowa
city: Lexington
country: United States
facility: VA Medical Center, Lexington
state: Kentucky
city: Shreveport
country: United States
facility: Overton Brooks VA Medical Center, Shreveport
state: Louisiana
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System
state: Minnesota
city: East Orange
country: United States
facility: VA New Jersey Health Care System, East Orange
state: New Jersey
city: Albany
country: United States
facility: VA Stratton Medical Center, Albany
state: New York
city: Bronx
country: United States
facility: VA Medical Center, Bronx
state: New York
city: Brooklyn
country: United States
facility: New York Harbor Health Care System, Brooklyn
state: New York
city: Buffalo
country: United States
facility: VA Western New York Healthcare System at Buffalo
state: New York
city: Syracuse
country: United States
facility: VA Medical Center, Syracuse
state: New York
city: Oklahoma City
country: United States
facility: VA Medical Center, Oklahoma City
state: Oklahoma
city: Portland
country: United States
facility: VA Medical Center, Portland
state: Oregon
city: Pittsburgh
country: United States
facility: VA Pittsburgh Health Care System
state: Pennsylvania
city: Providence
country: United States
facility: VA Medical Center, Providence
state: Rhode Island
city: Memphis
country: United States
facility: VA Medical Center, Memphis
state: Tennessee
city: Dallas
country: United States
facility: VA North Texas Health Care System, Dallas
state: Texas
city: Temple
country: United States
facility: Central Texas Veterans Health Care System
state: Texas
city: Hampton
country: United States
facility: VA Medical Center, Hampton
state: Virginia
city: Seattle
country: United States
facility: VA Puget Sound Health Care System, Seattle
state: Washington
city: Clarksburg
country: United States
facility: VA Medical Center, Clarksburg
state: West Virginia
city: Madison
country: United States
facility: Wlliam S. Middleton Memorial Veterans Hospital, Madison
state: Wisconsin
Study officials:
affiliation: Minneapolis Veterans Affairs Medical Center
name: Timothy J. Wilt, MD MPH
role: STUDY_CHAIR
References:
citation: Wilt T. Expectant management or early intervention for clinically localized prostate cancer? What we need are randomized trials. Clinical Care For Prostatic Diseases. 1994 Jan 6; 1:1-9.
citation: Moon TD, Brawer MK, Wilt TJ. Prostate Intervention Versus Observation Trial (PIVOT): a randomized trial comparing radical prostatectomy with palliative expectant management for treatment of clinically localized prostate cancer. PIVOT Planning Committee. J Natl Cancer Inst Monogr. 1995;(19):69-71. No abstract available.
citation: Wilt TJ, Brawer MK. Early intervention or expectant management for prostate cancer. The Prostate Cancer Intervention Versus Observation Trial (PIVOT): a randomized trial comparing radical prostatectomy with expectant management for the treatment of clinically localized prostate cancer. Semin Urol. 1995 May;13(2):130-6. No abstract available.
citation: Wilt TJ, Brawer MK. The Prostate Cancer Intervention Versus Observation Trial (PIVOT). Oncology (Williston Park). 1997 Aug;11(8):1133-9; discussion 1139-40, 1143.
citation: Wilt T. The importance of randomized treatment trials in early stage prostate cancer. New Developments in Prostate Cancer and Treatment. 1997 Feb 21; 2:29-35.
citation: Wilt TJ. Prostate cancer screening: practice what the evidence preaches. Am J Med. 1998 Jun;104(6):602-4. doi: 10.1016/s0002-9343(98)00127-2. No abstract available.
citation: Wilt TJ. Uncertainty in prostate cancer care: the physician's role in clearing the confusion. JAMA. 2000 Jun 28;283(24):3258-60. doi: 10.1001/jama.283.24.3258. No abstract available.
citation: Wilt TJ. Prostate carcinoma practice patterns: what do they tell us about the diagnosis, treatment, and outcomes of patients with prostate carcinoma? Cancer. 2000 Mar 15;88(6):1277-81. No abstract available.
citation: Wilt T. Editorial comment. Urology. 2001 Nov 1; 58(6):964-965.
citation: Wilt TJ. Clarifying uncertainty regarding detection and treatment of early-stage prostate cancer. Semin Urol Oncol. 2002 Feb;20(1):10-7. doi: 10.1053/suro.2002.30393.
citation: Wilt TJ. SPCG-4: a needed START to PIVOTal data to promote and protect evidence-based prostate cancer care. J Natl Cancer Inst. 2008 Aug 20;100(16):1123-5. doi: 10.1093/jnci/djn259. Epub 2008 Aug 11. No abstract available.
citation: Kaplan SA, McConnell JD, Roehrborn CG, Meehan AG, Lee MW, Noble WR, Kusek JW, Nyberg LM Jr; Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 ml or greater. J Urol. 2006 Jan;175(1):217-20; discussion 220-1. doi: 10.1016/S0022-5347(05)00041-8.
citation: Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, Gingrich JR, Wei JT, Gilhooly P, Grob BM, Nsouli I, Iyer P, Cartagena R, Snider G, Roehrborn C, Sharifi R, Blank W, Pandya P, Andriole GL, Culkin D, Wheeler T; Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012 Jul 19;367(3):203-13. doi: 10.1056/NEJMoa1113162.
citation: Wilt TJ. Implications of the prostate intervention versus observation trial (PIVOT). Asian J Androl. 2012 Nov;14(6):815. doi: 10.1038/aja.2012.103. Epub 2012 Sep 17. No abstract available.
citation: Wilt TJ. 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. J Natl Cancer Inst Monogr. 2012 Dec;2012(45):184-90. doi: 10.1093/jncimonographs/lgs041.
citation: Barry MJ, Andriole GL, Culkin DJ, Fox SH, Jones KM, Carlyle MH, Wilt TJ. Ascertaining cause of death among men in the prostate cancer intervention versus observation trial. Clin Trials. 2013;10(6):907-14. doi: 10.1177/1740774513498008. Epub 2013 Aug 29.
citation: Wilt TJ, Scardino PT, Carlsson SV, Basch E. Prostate-specific antigen screening in prostate cancer: perspectives on the evidence. J Natl Cancer Inst. 2014 Mar;106(3):dju010. doi: 10.1093/jnci/dju010. Epub 2014 Mar 4. No abstract available.
citation: Wilt TJ, Vo TN, Langsetmo L, Dahm P, Wheeler T, Aronson WJ, Cooperberg MR, Taylor BC, Brawer MK. Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT). Eur Urol. 2020 Jun;77(6):713-724. doi: 10.1016/j.eururo.2020.02.009. Epub 2020 Feb 21.
citation: Wilt TJ, Jones KM, Barry MJ, Andriole GL, Culkin D, Wheeler T, Aronson WJ, Brawer MK. Follow-up of Prostatectomy versus Observation for Early Prostate Cancer. N Engl J Med. 2017 Jul 13;377(2):132-142. doi: 10.1056/NEJMoa1615869.