RATIONALE: Watchful waiting until symptoms appear may be effective in patients with prostate cancer. It is not yet known if watchful waiting is more effective than prostatectomy for early prostate cancer.

PURPOSE: Randomized phase III trial to compare surgery with watchful waiting in men who have stage I or stage II prostate cancer.

OBJECTIVES:

• Compare the overall mortality rate in patients with clinically localized prostate cancer treated with radical prostatectomy and early intervention for subsequent disease progression vs expectant management with therapy reserved for palliation of symptomatic or metastatic disease.
• Compare the prostate cancer-specific survival of patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.
• Compare the progression-free survival of patients treated with these regimens.
• Determine the effects of radical prostatectomy on disease recurrence in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Within 6 weeks after randomization, patients undergo pelvic lymph node dissection (at the discretion of the urologist) followed within 2 weeks by radical prostatectomy. The choice of surgical procedure (retropubic, perineal, nerve sparing, or nonnerve sparing) is at the discretion of the urologist. Patients with metastases may undergo standard therapy, including prostatectomy, observation, orchiectomy or hormonal therapy, or radiotherapy. Patients with disease progression may undergo standard therapy, including hormonal therapy, radiotherapy, mechanical intervention, or observation.
• Arm II: Patients undergo expectant management with interventions reserved for symptomatic or metastatic disease. Asymptomatic disease progression (e.g., enlarging mass on digital rectal exam or imaging study, increase in PSA) without evidence of metastatic disease is not considered an indication for intervention. Patients with symptomatic local progression are treated first with alpha blockers or mechanical intervention (e.g., transurethral resection of the prostate (TURP), transurethral incision of the prostate, stent placement). Patients with symptomatic regional progression undergo mechanical intervention, radiotherapy, or hormonal therapy, as indicated. Hormonal therapy is considered first-line therapy for patients with disease progression requiring nonmechanical therapy. Patients with disease that continues to progress or fails to respond to hormonal therapy undergo radiotherapy or chemotherapy. Patients with symptomatic local disease progression (defined as recurrent and persistent gross hematuria or bladder outlet obstruction) despite TURP, stents, and alpha blockers may undergo prostatectomy.

Quality of life is assessed at baseline and then every 6 months.

Patients are followed every 3 months for 1 year and then every 6 months for 15 years.

PROJECTED ACCRUAL: A total of 1,050 patients will be accrued for this study within 7 years.

• Drug: chemotherapy
• Drug: endocrine-modulating drug therapy
• Procedure: conventional surgery
• Radiation: radiation therapy

• Wilt TJ, Brawer MK, Barry MJ, Jones KM, Kwon Y, Gingrich JR, Aronson WJ, Nsouli I, Iyer P, Cartagena R, Snider G, Roehrborn C, Fox S. 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 to watchful waiting for men with clinically localized prostate cancer. Contemp Clin Trials. 2009 Jan;30(1):81-7. Epub 2008 Aug 23.
• Wilt TJ, Brawer MK. The Prostate Cancer Intervention Versus Observation Trial (PIVOT). Oncology (Huntingt). 1997 Aug;11(8):1133-9; discussion 1139-40, 1143. Review.
• 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.
• 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.
• Wilt TJ, Brawer MK. The Prostate Cancer Intervention Versus Observation Trial: a randomized trial comparing radical prostatectomy versus expectant management for the treatment of clinically localized prostate cancer. J Urol. 1994 Nov;152(5 Pt 2):1910-4.
• [No authors listed] Screening for prostate cancer. American College of Physicians. Ann Intern Med. 1997 Mar 15;126(6):480-4. Review. No abstract available.

DISEASE CHARACTERISTICS:

• Adenocarcinoma of the prostate diagnosed within the past year

  • Clinically localized disease (T1a-c or T2a-c, NX, M0)
• PSA no greater than 50 ng/mL
• No evidence of metastatic disease on bone scan
• No evidence of nonlocalized disease on other imaging studies

PATIENT CHARACTERISTICS:

Age:

• 75 and under

Performance status:

• Not specified

Life expectancy:

• At least 10 years

Hematopoietic:

• Not specified

Hepatic:

• No severe hepatic impairment

Renal:

• Creatinine no greater than 3.0 mg/dL
• No severe renal impairment

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• No myocardial infarction within the past 6 months
• No unstable angina
• No other severe cardiac impairment

Pulmonary:

• No severe pulmonary impairment

Other:

• No other significant concurrent medical condition that is acute or debilitating or would increase risk
• No dementia
• No nondermatologic malignancy within the past 5 years

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for prostate cancer

Endocrine therapy:

• No prior hormonal therapy for prostate cancer
• No concurrent estrogens or antiandrogens

Radiotherapy:

• No prior radiotherapy for prostate cancer

Surgery:

• No prior surgery for prostate cancer except transurethral resection

Other:

• No concurrent participation in another intervention research study

• National Cancer Institute (NCI)
• Cancer and Leukemia Group B
• Southwest Oncology Group
• Eastern Cooperative Oncology Group