Is Death From Prostate Cancer the Right Clinical Endpoint to Guide Screening and Treatment Choices?

Jonathan D. Tward, MD, PhD
Published: Thursday, Jul 03, 2014
Huntsman Cancer Institute Jonathan D. Tward, MD, PhD
Jonathan D. Tward, MD, PhD
Assistant Professor,
Department of Radiation Oncology
Huntsman Cancer Institute at the University of Utah
Salt Lake City, UT
Alliance Partner Logo
There are few controversies in oncology as divisive as the value of prostate-specific antigen (PSA) screening and subsequent treatment for prostate cancer. Two widely reported and mature prospective trials, the European Randomized Study of Screening for Prostate Cancer (ERSPC)1 and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial,2 found marginal to no benefit for PSA screening with overall survival as the primary endpoint.

This led the US Preventive Services Task Force to recommend against PSA screening.

Specialty societies such as the American Academy of Family Practice, the American Society of Clinical Oncology, and the American Geriatric Society have issued warnings against PSA screening as part of their “Choosing Wisely” initiatives of the American Board of Internal Medicine Foundation.

So if the probable fate of a PSA-screened person is not death from prostate cancer, does the test have any merit? In the ERSPC trial 9.6% of men in the screened group and 6% of men in the control group were diagnosed with prostate cancer. This translates to a number needed to screen (NNS) of 28 persons to diagnose an additional prostate cancer. In the PLCO trial, the NNS was 89 persons. (The actual NNS is almost certainly lower due to contamination in the control groups of men who actually received PSA screening.) Interestingly, in the subgroup of men with minimal to no comorbidities, the NNS to prevent one prostate cancer death was only five persons.3

In order to know if identifying these cancers through screening was worthwhile absent a mortality benefit, we would have to know if screening otherwise maintained or improved quality of life.

Impact of “Conservative” Approach

In 2009, Lu-Yao and colleagues used the SEER-Medicare database4 to study the fate of men with localized prostate cancers who were initially put on a “conservative” management approach.

Like the randomized screening trials, prostate cancer deaths were uncommon, with fewer than 6% of these men dying of prostate cancer in the decade following the diagnosis. In PSA screen– diagnosed men aged 66 to 74 years with Gleason sum cancers of 5 to 7, six out of every 10 men were treated with androgen-deprivation therapy (ADT). One in 10 men were treated with palliative radiotherapy, chemotherapy, or spinal surgery. These treatments occurred within the first decade following diagnosis, and ADT was started within the first six months following diagnosis the majority of the time.

Revisiting Radical Treatment Strategy

If we further conclude that, most of the time, the fate of a patient with PSA screening–detected prostate cancer who does not choose a curative- intent treatment upfront leads to ADT—and a concomitant decrease in quality of life and potentially serious health problems—would treating them with a definitive therapy have altered the subsequent use of androgen deprivation and palliative therapy?

The Prostate Cancer Intervention Versus Observation Trial (PIVOT) trial,5 which tracks a mostly PSA-screened population randomized to surgery or observation, did report on nonmortality endpoints. Buried in the supplemental appendix to the publication is the finding of an absolute risk reduction of 6% in the prostatectomy group over the watch-and-wait group (number needed to treat of 17) to prevent bone metastasis.

Notable was the fact that this change in development of bone metastases was realized almost exclusively within the first eight years following diagnosis. The PIVOT trial has not reported on hormone therapy–free survival.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
35th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow® Clinical Vignette SeriesJan 31, 20192.0
Publication Bottom Border
Border Publication