BERKELEY, CA (UroToday.com) -
Commentary on the USPTF Conclusions regarding Prostate Cancer Screening and Treatment: Evidence Based or Biased?
It is clear that many men treated for prostate cancer are not benefitted. It is also clear that “active surveillance” is a viable option for many men with low-risk disease. Unfortunately, the United States Preventative Task Force's (USPTF) conclusions about treatment of prostate cancer are wholly inadequate and fundamentally flawed.[1] How did this happen?
First, they asked the wrong question. Second, the answers to this question resulted in biased conclusions about the merits of treatment. They asked “Key Question 3: What Are the Benefits of Treatment of Early-Staged or Screening-Detected Prostate Cancer?"
In their discussion of treatment for prostate cancer, they concluded that, “at the time of the USPSTF's commissioned evidence review, only one recent randomized, controlled trial of surgical treatment versus observation for clinically localized prostate cancer was available …,” and they went on to state, “… preliminary results were reported from another randomized trial that compared external beam radiotherapy (EBRT) with watchful waiting…,” and …"radiotherapy did reduce distant progression and recurrence-free survival.” They also concluded, “…preliminary findings from PIVOT show that, after 12 years, intention to treat with radical prostatectomy did not reduce disease-specific or all-cause mortality compared with observation…” They also concluded this section by noting that, “up to 0.5% of men will die within 30 days of having radical prostatectomy…radiation therapy is also associated with increases in erectile, bowel, and bladder dysfunction.” If these statements fairly and objectively summarize the state of evidence-based knowledge about treatment for prostate cancer, one should certainly wonder why any man should ever be treated.
Here are the problems:
- What is “early-staged or screening-detected prostate cancer? From the perspective of a medical oncologist, patients with clinically localized non-metastatic disease are considered “early.” In contrast, from the perspective of physicians who treat patients with clinically localized disease, “low-risk” patients are considered “early,” while others are considered either “intermediate” or “high risk.”[2] This latter form of “early” includes patients for whom active surveillance (AS) would be considered a viable option. The most favorable of these patients made up most of the patients entered on treatment versus no treatment trials -- both by design and because of ethical concern. Unfortunately the USPTF does not clarify the fact that their conclusions should only be limited to this subset of patients.
- When evaluating the benefits of treatment, why limit the studies on which conclusions are based to those with a “no treatment” arm? By deciding to arbitrarily make this decision, they end up excluding 98% of phase III randomized trials including men with clinically localized prostate cancer! This causes bias against treatment because the greatest benefits obtained from treatment are seen in the highest-risk patients. The studies they included had very few of such patients, thus creating tremendous bias.
In a recent JNCI review, we argued that there is a large and growing body of literature which demonstrates that, based on level I evidence, populations of men with prostate cancer can be defined who clearly benefit from treatment.[3] As is shown in the Tables 1-7 from this review, the number needed to treat (NNT) (in the positive studies) was generally quite low, supporting the notion that treatment for those who needed it is well justified by level I evidence. The USPTF conclusions imply quite the opposite.
References:
- Chou R, Croswell JM, Dana T, et al., Screening for Prostate Cancer: A Review of the Evidence for the U.S. Preventive Services Task Force. Annals of Internal Medicine, 2011 2.
- Mohler JL, Armstrong AJ, Bahnson RR, et al., Prostate cancer, Version 3.2012: featured updates to the NCCN guidelines. J Natl Compr Canc Netw 10:1081-7, 2012
- Roach M, 3rd, Thomas K: Overview of randomized controlled treatment trials for clinically localized prostate cancer: implications for active surveillance and the United States preventative task force report on screening? J Natl Cancer Inst Monogr 2012:221-9, 2012
Written by:
Mack Roach III, MD, FACR as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
UCSF-Helen Diller Family Comprehensive Cancer Center, San Francisco, CA USA
Overview of randomized controlled treatment trials for clinically localized prostate cancer: Implications for active surveillance and the United States preventative task force report on screening - Abstract
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