In addition, an ARR of 4.0% (95% CI; -0.2-8.3%, P = .06) was found for prostate cancer (PC)-specific mortality (7.4% vs. 11.4%). By comparison, the ARR for all-cause and cancer-specific mortalities in the 10-year follow-up analysis previously reported in The New England Journal of Medicine were 2.9% and 2.6%, respectively. On subgroup analysis, surgery reduced all-cause mortality among men with intermediate-risk disease (ARR = 14.5%, 95% CI 2.8%-25.6%). By contrast, no benefit was seen in the low- or high-risk groups. While surgery reduced the need for treatment of progressive disease, there were increased incidences of therapy-related long-term complications such as urinary incontinence and erectile and sexual dysfunction.
The PIVOT was the first prospective, randomized, controlled study to assess the impact of surgery in PC patients in the PSA screening era. Long-term follow-up of an earlier study in those with clinically diagnosed, localized PC demonstrated an ARR of 11% in cancer-specific survival in the surgically treated group.2 However, with the advent of PSA screening and the ensuing stage migration, the benefit of prostatectomy in clinically low-risk PC was called into question. The original analysis of the PIVOT demonstrated a lack of benefit in patients with clinically low-risk PC. Based on this conclusion, the strategy of active surveillance has been increasingly adopted in the management of low-risk localized PC.
However, the implications of the PIVOT results for intermediate- and high-risk PC remain hotly debated.3-6 When separated into the different D’Amico risk classifications, surgery attenuated all-cause mortality in the intermediate-risk group and cancer-specific mortality in the high-risk group.1 Taken together, the PIVOT was interpreted by many as an affidavit for the futility of surgical treatment for PC. Even with longer follow-up, many weaknesses in the trial design deserve mention.
The PIVOT was created to demonstrate a 25% relative reduction in mortality. To put this in perspective, early coronary artery bypass graft versus medical management demonstrated a mere 17% relative reduction in overall mortality.7 To achieve such a lofty objective, selection criteria to include patients with minimal competing risks were of paramount importance. The overall mortality rates at the 10-year analysis were 47.0% and 49.9% in the treatment and control groups, respectively. These rates were high compared with age-matched subjects in the general population (20.6%), indicating a higher incidence of comorbidities.8 In the face of these restrictions, the enrollment in the trial fell short of the numbers needed to demonstrate statistical difference.4 In addition to these shortfalls, the intent-to-treat analysis was marred by a 20.5% incidence of definitive treatment in the observation arm. While longer follow-up incrementally added to the strength of the analysis, many of the abovementioned deficiencies could not be rectified.
Notwithstanding the PIVOT’s inadequacies, the trial remains a benchmark study, pointing to the critical importance of uncoupling treatment from diagnosis in the PSA era as well as the need for more accurate characterization of the different risk categories of disease.
Presented By: Timothy Wilt, MD, MPH, Minneapolis VA Center for Chronic Disease Outcomes Research, Minneapolis, MN
Written By: Roger Li, MD, Urologic Oncology Fellow, University of Texas MD Anderson Cancer Center, @UrogerliMD, and Ashish M. Kamat, MD, Wayne B. Duddlesten Professor, University of Texas MD Anderson Cancer Center
at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA
1. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367(3):203-213.
2. Bill-Axelson A, Holmberg L, Garmo H, et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014;370(10):932-942.
3. Sartor O. Implications of the prostate intervention versus observation trial (PIVOT). Asian J Androl. 2012;14(6):803-804.
4. Thompson IM Jr, Tangen CM. Prostate cancer — uncertainty and a way forward. N Engl JMed. 2012;367(3):270-271.
5. Weinberg AE, Brooks JD. PIVOT and the challenges of localized prostate cancer care. Transl Androl Urol. 2012;1(3):141-143.
6. Wilt TJ. Implications of the prostate intervention versus observation trial (PIVOT). Asian J Androl. 2012;14(6):815.
7. Yusuf S, Zucker D, Peduzzi P, et al. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet. 1994;344(8922):563-570.
8. Shikanov S, Kocherginsky M, Shalhav AL, Eggener SE. Cause-specific mortality following radical prostatectomy. Prostate Cancer Prostatic Dis. 2012;15(1):106-110.