Active Surveillance in Younger Men With Prostate Cancer

Reviewed by Dr. Chad Guenther
Leapman MS, et al. JCO. 2017 June 10;35(17):1894-1904

SUMMARY
The objective of this study was to determine the effect of age on surveillance outcomes for men with prostate cancer (PCa) on active surveillance (AS). The UCSF Urologic Oncology Database is a departmental database containing prospectively accrued data for patient with urologic cancers. Consenting individuals on AS with ≥6 months of follow-up were analyzed with data beginning in 1992. Institutional eligibility for AS including Gleason score (GS) ≤ 3+3, prostate specific antigen (PSA) ≤ 10 ng/mL, clinical stage ≤ T2, ≤ 33% of biopsy core specimen involvement, and no single core with > 50% involvement. AS consisted of PSA measurement every 3 months, confirmational biopsy within 12 months of original biopsy, transrectal ultrasound-guided biopsy every 12-24 months, and institutional pathologist review of outside biopsies if diagnosis was made outside of UCSF (74% of cases). Radical prostatectomy (RP) was offered if there was Gleason score upgrade (GSU), increase in tumor volume, increase in PSA, increase in clinical stage, patient anxiety, or patient preference. Date of diagnosis was defined as the date of first biopsy. Primary endpoint was GSU on biopsy to GS > 3+3. Secondary endpoints were biopsy-determined progression by GSU at biopsy or increase in volume > 33% of biopsy core specimens, rates of definitive treatment, PSA > 0.2 on 2 measurements after delayed RP, or salvage treatment with detectable PSA. Younger patients were defined as ≤ 60 years of age.

Data from 1433 men were reviewed with median follow-up of 49 months and median age of 63 (42% ≤ 60). GS was ≤ 3+3 in 89% of men. Overall, younger men had lower PSA and more frequent GS of 3+3. No GSU was detected by biopsy in 73% versus 64% in younger versus older men respectively at 3 years (p < 0.01) and 55% versus 48% at 5 years (p < 0.01). Younger age was independently associated with decreased risk of GSU (HR 0.969 for each decrease in year at diagnosis, 95% CI 0.956-0.983, p < 0.01) and biopsy-proven progression (HR 0.981 for each decrease in year at diagnosis, 95% CI 0.970-0.993, p < 0.01). Younger age compared to older age had decreased risk of biopsy-proven GSU (HR 0.67, 95% CI 0.55-0.83, p < 0.01) and decreased risk of biopsy-proven progression (HR 0.78, 95% CI 0.65-0.92, p < 0.01). Age groups had similar rates of definitive treatment, with 320 (22%) undergoing RP (64% due to progression, 6% with intermediate risk at diagnosis, 3% with PSA doubling in < 36 months). Eighty-four (26%) underwent RP in the absence of progression by PSA or biopsy.

COMMENTARY
Screening for and treatment of PCa has come under increasing scrutiny in recent years with some asserting that the disease is over-treated. AS is a management strategy wherein the patient is observed closely for signs or changes consistent with disease progression warranting definitive therapy. AS has been advocated as a strategy to avoid overtreatment in the setting of low-risk PCa. Given the natural history of cancer, there are some who feel that delaying definitive treatment might result in missing the opportunity for a cure. This would be especially concerning in younger patients who may otherwise have decades to live. However, younger patients may suffer from a greater overall decrease in quality of life if treated prematurely, especially given the morbidities associated with RP and baseline higher functional statuses.

This study adds to the increasing body of evidence that delaying definitive treatment in younger patients may not contribute to worsening outcomes when adequately monitored. The implications of this are broad. Perhaps most importantly, AS helps reduce over-treatment. Delaying definitive surgery may also preserve QOL in younger patients without an increased risk of progression. Furthermore, a reduction in over-treatment may help relieve some of the concerns associated with PSA screening in younger patients.

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