EAU 2018: Assessing the external validity of the updated prostate cancer intervention versus observation trial (PIVOT)

Copenhagen, Denmark (UroToday.com) Dr. Abdollah and colleagues from Henry Ford Hospital in Detroit reported their results assessing the external validity of the updated PIVOT trial. The PIVOT study [1] has been instrumental in shaping health policy and public discourse about treatment of prostate cancer in the US. However, concerns have been raised about the external validity of this trial to men diagnosed with prostate cancer in the US [2]. The objective of this study was to assess the updated PIVOT trial’s [3] generalizability (external validity) to men who were diagnosed with prostate cancer using three nationally representative databases.

For this study, the authors used data of men diagnosed with prostate cancer within the Surveillance, Epidemiology, and End-Results (SEER; population based registry) 2000-2004, National Cancer Database (NCDB; hospital based registry) 2004-2005, and Prostate, Lung, Colorectal and Ovarian (PLCO) trial between 1993-2001. Only men undergoing surgery or observation who satisfied the inclusion criteria of PIVOT were included in the study. Within SEER, men were excluded from the comparative analyses if surgery was not recommended (because of pre-existing conditions or otherwise): these men were separately assessed for age at diagnosis and overall mortality. Chi-square test and ANOVA test were used to compare proportions and means, respectively.

A total of 2,847 (PLCO), 60,089 (SEER), and 63,303 (NCDB) prostate cancer patients were included in the analysis. Mean age (standard deviation(SD)) at diagnosis of clinically localized prostate cancer for men in PIVOT was 67.0 (5.2) years, compared to 65.8 (4.5), 61.3 (7.3) and 60.2 (7.0) in PLCO, SEER and NCDB respectively (p<0.001). The majority of men (94-96.4%) in PLCO and NCDB had Charlson comorbidity index (CCI) of 0, compared to only 56% for men in PIVOT (p<0.001). A limitation is that no comorbidity data are available in the SEER database. Patients in PIVOT were more likely to have well-differentiated histological grade (21.5%) on pathologic review compared to the other databases (1.2-5.9%, p<0.001). Overall mortality was 64% in PIVOT (over a median 12.7-year follow-up) vs. 8-23% in the three examined cohorts (over a median 12.3-year follow-up). Interestingly, within SEER, the mean age at diagnosis for men who were not recommended surgery was 65.1 years, with overall mortality 50% over a median follow-up of 12.5 years.

Dr. Abdollah concluded that these findings across multiple large datasets consistently demonstrate that men within PIVOT were older and sicker than their counterparts across the US. The reported overall survival in PIVOT was worse even when compared to men within SEER who were not recommended definitive treatment. The authors note that these findings suggest a sampling bias, and highlight the lack of generalizability, and thus external validity, of PIVOT findings to men diagnosed with clinically localized prostate cancer in the US.

Speaker: Firas Abdollah, Vattikuti Urology Institute, Henry Ford Hospital, Detroit, USA

Co-Authors: Dalela D, Akshay S, Alanee S, Keeley J, Peabody J, Rogers C, Mani M

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md, at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark


1. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012;367:203-213.
2. Wallis CJD, Klotz L. Prostatectomy versus Observation for Early Prostate Cancer. N Engl J Med 2017;377(13):1301-1302.
3. Wilt TJ, Jones KM, Barry MJ, et al. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med 2017;377(2):132-142.

EAU 2018: Analysis shows influential US prostate study not representative of real-world patients