Prostate Cancer Intervention Versus Observation Trial (PIVOT)

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00007644
• Collaborator: Agency for Healthcare Research and Quality (AHRQ) (U.S. Fed), National Cancer Institute (NCI) (NIH)
• Enrollment: 731
• Locations: 31
• Arms: 2
• Duration (Months): 182
• Patients Per Site: 23.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Procedure: Radical prostatectomy	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 731 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Nov 1, 1994
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Other: Radical Prostatectomy Surgical removal of the prostate	Procedure: Radical prostatectomy; Surgical removal of the prostate
No Intervention: Watchful Waiting Closely watching, waiting and treating symptoms if and when cancer progresses

Outcome Measures

Primary Outcome Measures

1. All Cause Mortality [From date of randomization until date of death from any cause, assessed until end of study, up to 16 years]

   Number of deaths from any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Medical Center, Birmingham	Birmingham	Alabama	United States	35233
2	Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock	North Little Rock	Arkansas	United States	72114-1706
3	VA Medical Center, Long Beach	Long Beach	California	United States	90822
4	VA Medical Center, San Francisco	San Francisco	California	United States	94121
5	VA Greater Los Angeles HCS, Sepulveda	Sepulveda	California	United States	91343
6	James A. Haley Veterans Hospital, Tampa	Tampa	Florida	United States	33612
7	VA Medical Center, Boise	Boise	Idaho	United States	83702
8	Jesse Brown VAMC (WestSide Division)	Chicago	Illinois	United States	60612
9	Richard Roudebush VA Medical Center, Indianapolis	Indianapolis	Indiana	United States	46202-2884
10	VA Medical Center, Iowa City	Iowa City	Iowa	United States	52246-2208
11	VA Medical Center, Lexington	Lexington	Kentucky	United States	40502
12	Overton Brooks VA Medical Center, Shreveport	Shreveport	Louisiana	United States	71101
13	VA Ann Arbor Healthcare System	Ann Arbor	Michigan	United States	48113
14	Minneapolis VA Health Care System	Minneapolis	Minnesota	United States	55417
15	VA New Jersey Health Care System, East Orange	East Orange	New Jersey	United States	07018
16	VA Stratton Medical Center, Albany	Albany	New York	United States	12208
17	VA Medical Center, Bronx	Bronx	New York	United States	10468
18	New York Harbor Health Care System, Brooklyn	Brooklyn	New York	United States	11209
19	VA Western New York Healthcare System at Buffalo	Buffalo	New York	United States	14215
20	VA Medical Center, Syracuse	Syracuse	New York	United States	13210
21	VA Medical Center, Oklahoma City	Oklahoma City	Oklahoma	United States	73104
22	VA Medical Center, Portland	Portland	Oregon	United States	97201
23	VA Pittsburgh Health Care System	Pittsburgh	Pennsylvania	United States	15240
24	VA Medical Center, Providence	Providence	Rhode Island	United States	02908
25	VA Medical Center, Memphis	Memphis	Tennessee	United States	38104
26	VA North Texas Health Care System, Dallas	Dallas	Texas	United States	75216
27	Central Texas Veterans Health Care System	Temple	Texas	United States	76504
28	VA Medical Center, Hampton	Hampton	Virginia	United States	23667
29	VA Puget Sound Health Care System, Seattle	Seattle	Washington	United States	98108
30	VA Medical Center, Clarksburg	Clarksburg	West Virginia	United States	26301
31	Wlliam S. Middleton Memorial Veterans Hospital, Madison	Madison	Wisconsin	United States	53705

Sponsors and Collaborators

• VA Office of Research and Development
• Agency for Healthcare Research and Quality (AHRQ)
• National Cancer Institute (NCI)

Investigators

• Study Chair: Timothy J. Wilt, MD MPH, Minneapolis Veterans Affairs Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT00007644
• Other Study ID Numbers: 407; NCT00002606
• First Posted: Jan 1, 2001
• Last Update Posted: Feb 24, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by VA Office of Research and Development: cancer of the prostate (CAP); cancer treatment; chronic diseases; expectant management; genitourinary; prostate; prostate specific cancer mortality; radical prostatectomy
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	Enrollment begain in November 1994 and ended in January 2002 with follow-up through January 2010. We recruited men from 44 Department of Veterans Affairs sites and 8 National Cancer Institute sites.
Pre-assignment Detail	A total of 13,022 men were entered into study logs as potentially eligible. Based upon further chart review, 6707 met age, comorbidity and prostate cancer specific criteria and received detailed information about the study. From these, 5023 were considered likely to be eligible and a total of 731 men agreed to participate.

Arm/Group Title	Radical Prostatectomy	Watchful Waiting
Arm/Group Description	Surgical removal of the prostate	Closely watching, waiting and treating symptoms if and when cancer progresses
Period Title: Overall Study
STARTED	364	367
COMPLETED	364	367
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Radical Prostatectomy	Watchful Waiting	Total
Arm/Group Description	Surgical removal of the prostate	Closely watching, waiting and treating symptoms if and when cancer progresses	Total of all reporting groups
Overall Participants	364	367	731
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	122 33.5%	131 35.7%	253 34.6%
>=65 years	242 66.5%	236 64.3%	478 65.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.0 (5.2)	66.8 (5.6)	66.9 (5.4)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	364 100%	367 100%	731 100%
Region of Enrollment (participants) [Number]
United States	364 100%	367 100%	731 100%

Outcome Measures

1. Primary Outcome

Title	All Cause Mortality
Description	Number of deaths from any cause.
Time Frame	From date of randomization until date of death from any cause, assessed until end of study, up to 16 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radical Prostatectomy	Watchful Waiting
Arm/Group Description	Surgical removal of the prostate Radical prostatectomy: Surgical removal of the prostate	Closely watching, waiting and treating symptoms if and when cancer progresses
Measure Participants	364	367
Count of Participants [Participants]	171 47%	183 49.9%

Adverse Events

Arm/Group Title	Radical Prostatectomy		Watchful Waiting
Arm/Group Description	Surgical removal of the prostate		Closely watching, waiting and treating symptoms if and when cancer progresses
All Cause Mortality
	Radical Prostatectomy		Watchful Waiting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Radical Prostatectomy		Watchful Waiting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	171/364 (47%)		183/367 (49.9%)
General disorders
Death	171/364 (47%)	171	183/367 (49.9%)	183
Other (Not Including Serious) Adverse Events
	Radical Prostatectomy		Watchful Waiting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/364 (0%)		0/367 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.