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Active surveillance of prostate cancer associated with favorable outcomes in younger men

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May 1, 2017

Younger age was associated with lower risks for disease progression and biopsy-based Gleason score upgrades during active surveillance of low- or intermediate-risk prostate cancer, according to a study published in Journal of Clinical Oncology.

“The results of this study indicate that younger patients with low-risk prostate cancer experienced favorable outcomes when managed with active surveillance at nearly 5-year median follow-up,” Michael Leapman, MD, assistant professor in the department of urology at Yale University School of Medicine, told HemOnc Today. “Younger patients have conventionally been counseled to receive definitive treatment, even in the setting of low-risk disease. This study is impactful as it may expand the use of surveillance, potentially limiting the harms of overtreatment for patients with screening-detected low-grade tumors.”

Michael Leapman

Active surveillance is a management strategy consisting of close, periodic disease observation with the opportunity for delayed definitive therapy with curative intent. Despite historical patterns indicating high rates of initial primary treatment of patients with low-risk disease, trends show an increased use of active surveillance, with estimates of nearly 40% of American men with low-risk prostate cancer choosing this option.

Leapman and colleagues identified 1,433 patients (median age at diagnosis, 63 years; interquartile range [IQR], 57-68) undergoing active surveillance who had a PSA concentration at diagnosis at or below 10 ng/mL. At diagnosis, men had Gleason scores of 3 + 3 or lower (n = 1,258; 89%) or 3 + 4 (n = 137; 10%).

Active surveillance involved PSA testing at 3-month intervals and biopsies within 12 months, as well as transrectal ultrasound–guided surveillance biopsy procedures every 12 to 24 months based on clinical risk and disease trajectory.

The association between younger patient age and biopsy-based Gleason score upgrade — defined as any increase to 3 + 4 or higher — served as the study’s primary endpoint. Biopsy-determined progression, the rates of definitive treatment and biochemical recurrence after delayed radical prostatectomy served as secondary endpoints.

Researchers divided patients into groups based on age 60 years or younger (n = 599; 42%) or 61 years and older (n = 834; 58%). Compared with men aged 61 years or older, younger patients had lower PSA levels at diagnosis (median, 5 ng/mL vs. 5.6 ng/mL; P < .01) and a more frequent Gleason pattern of 3 + 3 (93% vs. 85%; P < .01).

Median follow-up was 49 months (IQR, 26-80).

Biopsy-based Gleason score upgrade-free rates were higher among younger men at 3 years (73% vs. 64%) and 5 years (55% vs. 48%; P < .01).

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On Cox regression analysis, younger age was independently associated with lower risk for biopsy-based Gleason score upgrades (HR per 1-year decrease = 0.96; 95% CI, 0.95-0.98). This association persisted upon restriction to men meeting strict active surveillance inclusion criteria.

The treatment-free survival rates were similar among younger and older men at 3 years (78% vs. 74%) and 5 years (65% vs. 64%).

Among those who underwent definitive treatments, a greater proportion of older men than younger men received radiation therapy (38% vs. 21%); however, fewer older men received delayed radical prostatectomies (58% vs. 78%; P < .01 for both).

However, there was no significant association between younger age and risks for definitive treatment or biochemical recurrence after delayed radical prostatectomy.

Researchers acknowledged their analysis lacked complete longitudinal health-related quality-of-life data, which prevented a direct comparison of urinary, sexual function and psychologic outcomes by age.

“The study findings indicate that patient age should not serve as a singular factor in determining eligibility for surveillance, but should be comprised of a broader appraisal of risk,” Leapman said. “By demonstrating comparatively favorable outcomes in terms of freedom from biopsy upgrade, these findings stand to improve the understanding of the viability of surveillance in younger patients.”

Earlier in April, the U.S. Preventive Services Task Force amended its recommendation on prostate cancer screening, stating that men aged 55 to 69 years should speak with their clinicians about the potential benefits and harms of PSA tests.

“Active surveillance stands to mitigate the harms of overtreatment for those with incidentally detected low-grade cancers and its use has significantly increased nationally in recent years,” Leapman said. “As the focus on screening continues to shift toward younger patients, the use of surveillance in this population may be an important strategy to limit overtreatment.”

Increasing the use of active surveillance in patients with low-risk prostate cancer has the potential to improve health-related quality of life and reduce treatment burden and costs, Mark Garzotto, MD, urologic oncologist at Veterans Administration Portland Health Care System and Oregon Health & Science University, wrote in an accompanying editorial.

“It is important for clinicians to understand and explain to the younger patient that he concurrently has the most to gain and the most to lose,” Garzotto wrote. “Prior PSA–era studies have examined the safety of active surveillance in younger men and it seems efficacious in properly selected men. However, it is important to have clear and realistic expectations set for young men who choose to undergo active surveillance and, in turn, agree to undergo regimented monitoring of their condition.

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“Future advancements in surveillance for disease progression will likely come from innovations in promising areas such as MRI, blood and tissue markers, which must then be prospectively validated in well-designed clinical trials,” he added. – by Chuck Gormley

For more information:

Michael Leapman, MD, can be reached at Department of Urology, Yale University School of Medicine, 789 Howard Ave., Fitkin 300, New Haven, CT 06520; e-mail: michael.leapman@yale.edu.

Disclosure: U.S. Department of Defense Transformative Impact Aware Prostate Cancer Research Program, the Urological Research Foundation, and the NCI funded this study. Leapman reports no relevant financial disclosures. Garzotto reports a consultant role with Bayer. Please see the full study for a list of all other researchers’ relevant financial disclosures.

itj+ Infographic

Infographic shows outcomes of active surveillance in men with prostate cancer

itj+ Perspective