Prostate Ca: Some Younger Men Candidates for Active Surveillance (CME/CE)

FG_AUTHORS: MedPage Today

Action Points

  • Younger age at diagnosis of low-risk prostate cancer was independently associated with decreased risk of disease progression in men managed with active surveillance.
  • Note that importantly, age was not associated with time to treatment or subsequent clinical recurrence after delayed radical prostatectomy at 5 years, reinforcing the feasibility of initial active surveillance for younger patients with prostate cancer.

Younger age at diagnosis of low-risk prostate cancer was independently associated with decreased risk of disease progression in men managed with active surveillance, researchers reported.

Among 1,433 men with clinical low- and intermediate-risk prostate cancer, compared with the 58% of participants diagnosed when they were older than 60, those diagnosed at or before age 60 had a 7% reduction (55% versus 48%) in the rate of progression (as assessed by biopsy-based Gleason score upgrade-free rates) during 5 years of active surveillance (P<0.01), the authors wrote online in the Journal of Clinical Oncology.

On Cox regression analysis, younger age was independently associated with lower risk of biopsy-based Gleason score upgrade (hazard ratio per 1-year decrease, 0.97 [95% CI 0.956 to 0.983]; P<0.01), which persisted in an analysis restricted to the 66% of men who met strict active surveillance inclusion criteria, noted Michael Leapman, MD, of Yale University School of Medicine, and colleagues.

Importantly, age was not associated with time to treatment or subsequent clinical recurrence after delayed radical prostatectomy at 5 years, reinforcing the feasibility of initial active surveillance for younger patients with prostate cancer.

"At diagnosis, appropriately risk-stratified patients may be counseled that in the short to intermediate term, younger age was not associated with worse surveillance outcomes assessed by biopsy outcome and recurrence-free survival after delayed treatment," Leapman noted, cautioning that "longer follow-up is needed to assess more distant outcomes."

Study participants included 1,433 individuals choosing active surveillance beginning in 1992, with a minimum follow-up of 6 months from the time of initial diagnostic biopsy. Patients were a median of 63 years old at baseline, were followed for a median of 49 months, and most (89%) had a Gleason score at diagnosis of at least 3+3.

Significant baseline differences in the younger patient group included lower prostate-specific antigen (PSA) values, lower Gleason scores, and lower Cancer of the Prostate Risk Assessment scores.

Active surveillance has been shown to safely mitigate overtreatment of low-risk prostate cancer in this era of PSA screening, and as noted recently in MedPage Today, is increasingly if inconsistently used.

In the absence of standardized surveillance protocols, the younger cohort in this study received more surveillance biopsies than those over 60 in the same interval (median of three versus two; P<0.01), and similar numbers of PSA tests (median of 10 versus nine; P=0.27).

"From this perspective, the lower risks of progression despite greater scrutiny (i.e., an approximately 30% lower risk of upgrading over time) should be informative to counsel younger patients with low-risk prostate cancer who are considering initial management with surveillance," the authors suggested.

Given the higher baseline sexual and urinary function at the time of diagnosis, younger patients stand to lose the most by immediate treatment -- yet age remains an empirical driver of treatment decisions, "favoring early treatment in younger individuals."

Indeed, older patients in the study were more likely to receive radiation therapy than younger patients were (38% versus 21%) and were less likely than their younger counterparts to receive radical prostatectomy (58% versus 78%; P<0.01 for both), although these differences were not significantly associated with age after adjustment.

"Increasing the thoughtful application of active surveillance in patients with low-risk prostate cancer has the potential for benefits to healthcare systems as a whole, including improved health-related quality of life, reductions in treatment burden, and reduced costs," commented Mark Garzotto, MD, of the Veterans Administration Portland Health Care System in Oregon, writing in an accompanying editorial.

Reiterating the authors' acknowledgement that age only "marginally" improved the performance of multifactor risk models, Garzotto suggested that younger age may be better used to predict individual patient risk.

Evaluation should consider current health status, known risk factors for progression, and age, Garzotto noted. "It is important for clinicians to understand and explain to the younger patient that he concurrently has both the most to gain and the most to lose."

Leapman and colleagues wrote that although there is no consensus on the optimal screening approach, a growing body of literature supports obtaining an initial baseline screening at a young age -- as young as 45 -- and basing subsequent screens on this initial result.

Garzotto said that limitations to the study included the fact that a lower rate of cancer progression was seen in one in four patients referred externally (hazard ratio, 0.754; 95% CI, 0.60 to 0.95). "More information is needed to determine if they represent a random sample of the population or a selected group with more favorable underlying risk features."

Additional limitations included the increased proportion of younger than older patients who had lower-risk disease profiles and an initial diagnosis outside the authors' institution, and that the median follow-up duration after prostatectomy of 41 months may have underestimated the rates of recurrence.

The study was supported by the U.S. Department of Defense Transformative Impact Aware Prostate Cancer Research Program, the National Cancer Institute, and the Urological Research Foundation.

Leapman reported having no relationships to disclose; several co-authors reported relevant relationships with industry.

Garzotto disclosed relationships with Bayer, and through his institution, with Merck Sharp & Dohme, Astellas Medivation, Genomic Health, and Dendreon.

  • Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

2017-06-16T09:30:00-0400

Read more http://www.medpagetoday.com/HematologyOncology/ProstateCancer/66075

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