Outcomes Research in Review

Follow-up of Prostatectomy versus Observation for Early Prostate Cancer

Wilt T, Jones K, Barry M, et al. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med 2017;377:132–42.



Objective. To determine differences in all-cause and prostate cancer–specific mortality between subgroups of patients who underwent watchful waiting versus radical prostactectomy (RP) for early-stage prostate cancer.

Design. Randomized prospective multicenter trial (PIVOT study).

Setting and participants. Study participants were Department of Veterans Affairs (VA) patients younger than age 75 with biopsy-proven local prostate cancer (T1–T2, M0 by TNM staging and centrally confirmed by pathology laboratory in Baylor) between November 1994 and January 2002. They were patients at NCI medical center–associated VA facilities. Patients had to be eligible for RP and not limited by concomitant medical comorbidities. Patients were excluded if they had undergone therapy for prostate cancer other than transurethral resection of prostate cancer (TURP) for diagnostic purposes including radiation, androgen deprivation theory (ADT), chemotherapy, or definitive surgery. They were also excluded if they had a PSA > 50 ng/mL or a bone scan suggestive of metastatic disease.

Main outcome measures. The primary outcome of the study was all-cause mortality. The secondary outcome was prostate cancer–specific mortality. These were measured from date of diagnosis to August 2014 or until the patient died. A third-party end-points committee blinded to patient arm in the trial determined the cause of death from medical record assessment.

Main results. 731 men with a mean age of 67 were randomly assigned to RP or watchful waiting. The median PSA of patients was 7.8 ng/mL with 75% of patients having a Gleason score ≤ 7 and 74% of patients having low- or intermediate-risk prostate cancer. As of August 2014, 468 of 731 men had died; cause of death was unavailable in 7 patients (2 patients in the surgery arm and 5 in the observation arm). Median duration of follow-up to death or end of follow-up was 12.7 years. All-cause mortality was not significantly different between RP and observation arms (hazard ratio 0.84, 95% confidence interval [CI] 0.7–1.01, P = 0.06). The incidence of death at 19.5 years was 61.3% in patients assigned to surgery versus 66.8% in the watchful waiting arm (relative risk 0.92, 95% CI 0.82–1.02). Deaths from prostate cancer or treatment occurred in 69 patients in the study; 65 from prostate cancer and 4 from treatment. Prostate cancer–associated mortality was not significantly lower in the RP arm than in the watchful waiting arm (hazard ratio 0.63, 95% CI 0.39–1.02, P = 0.06). Mortality was not significantly reduced in any examined subgroup (age > or < 65, white or black ethnicity, PSA > 10 ng/mL or < 10 ng/mL, low/high/intermediate grade, Gleason score). Fewer men who underwent surgery (40.9%) had progression compared to those who underwent observation (68.4%). Most of these patients experienced local progression: 34.1% in the surgery arm and 61.9% in the observation arm. Distant progression was seen in 10.7% of patients treated with RP and 14.2% in the untreated arm. Treatment for progression (local, asymptomatic or by PSA rise) occurred in 59.7% of men assigned to observation and in 33.5% of men assigned to surgery. ADT was more frequently utilized as a treatment modality in men who were initially observed (44.4%) than in men who had up-front surgery (21.7%).

With regard to patient-related outcomes (PROs), more men assigned to RP reported bothersome symptoms such as physical discomfort and limitations in performing activities of daily living (ADLs) at 2 years than in men who did not undergo the intervention. This difference did not persist at later time points beyond 2 years. The use of incontinence pads was markedly higher in surgically treated men than in untreated men. 40% of patients in the treatment arm had to use at least 1 incontinence pad per day within 6 months of RP; this number remained unchanged at 10 years. Rates of erectile dysfunction were reported as lower at 2 (80% versus 45%), 5 (80% versus 55%) and 10 (85% versus 70%) years in men who were watched versus those who underwent surgery. Rates of optimal sexual function were reported as lower in resected men at 1 (35% versus 65%), 5 (38% versus 55%) and 10 (50% versus 70%) years than in men who were watched.

Conclusion. Patients with localized prostate cancer who were randomized to observation rather than RP did not experience greater all-cause mortality or prostate cancer–specific mortality than their surgical counterparts. Furthermore, they experienced less erectile dysfunction, less sexual function impairment, and less incontinence than patients who underwent surgery. Patients who underwent surgery had higher rates of ADL dysfunction and physical discomfort although these differences did not persist beyond 2 years.


Nearly 162,000 men will be diagnosed with prostate cancer in 2017, and it is anticipated 27,000 will succumb to their disease [1]. This ratio of incident cases to annual mortality represents one of the lowest ratios amongst all cancer sites and suggests most prostate cancers are indolent. Localized prostate cancer is usually defined by low (Gleason score ≤ 6, PSA < 10 ng/mL and ≤ T2 stage) or intermediate (Gleason score ≤ 7, PSA 10–20 ng/mL, and ≤ T2b stage) risk characteristics. 70% of patients present with low-risk disease, which carries a mortality risk of close to 6% at 15 years [2]. Despite this, nearly 90% of these patients are treated with RP, external beam radiation, or brachytherapy. Some published studies suggest up to 60% of low-risk prostate cancer patients may be overtreated [3,4]. The decision to treat low-risk patients is controversial, as morbidities (eg, sexual dysfunction, erectile dysfunction, incontinence) from a radical prostatectomy or focal radiation therapy are significant while the potential gain may be minimal.

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