Intermediate and Longer-Term Outcomes From a Prospective Active-Surveillance Program for Favorable-Risk Prostate Cancer

Abstract

Purpose: To assess long-term outcomes of men with favorable-risk prostate cancer in a prospective, active-surveillance program.

Methods: Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy. Primary outcomes were overall, cancer-specific, and metastasis-free survival. Secondary outcomes were the cumulative incidence of reclassification and curative intervention. Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model.

Results: A total of 1,298 men (median age, 66 years) with a median follow-up of 5 years (range, 0.01 to 18.00 years) contributed 6,766 person-years of follow-up since 1995. Overall, cancer-specific, and metastasis-free survival rates were 93%, 99.9%, and 99.4%, respectively, at 10 years and 69%, 99.9%, and 99.4%, respectively, at 15 years. The cumulative incidence of grade reclassification was 26% at 10 years and was 31% at 15 years; cumulative incidence of curative intervention was 50% at 10 years and was 57% at 15 years. The median treatment-free survival was 8.5 years (range, 0.01 to 18 years). Factors associated with grade reclassification were older age (hazard ratio [HR], 1.03 for each additional year; 95% CI, 1.01 to 1.06), prostate-specific antigen density (HR, 1.21 per 0.1 unit increase; 95% CI, 1.12 to 1.46), and greater number of positive biopsy cores (HR, 1.47 for each additional positive core; 95% CI, 1.26 to 1.69). Factors associated with intervention were prostate-specific antigen density (HR, 1.38 per 0.1 unit increase; 95% CI, 1.22 to 1.56) and a greater number of positive biopsy cores (HR, 1.35 for one additional positive core; 95% CI, 1.19 to 1.53).

Conclusion: Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention.

Fig 1.

CONSORT diagram for the Johns Hopkins active surveillance program. (*) Treatment is recommended in all cases of grade reclassification (ie, Gleason score upgrading). (†) Death from nonprostate cancer (PCA) causes. (‡) Includes five men who died of non-PCA causes after treatment. (§) Includes 27 men who were undecided on treatment at the time of analysis, eight men with no treatment data available, and two men who were found to have metastatic disease shortly after grade reclassification and subsequently died of PCA without treatment of their local disease. (‖) Includes four men who died of non-PCA causes after treatment. (¶) Includes 54 men who elected continued observation and 15 men with no treatment data available.

Fig 2.

Cumulative hazard of death as a result of any cause (dashed line) and prostate cancer death or metastasis (solid line).

Fig 3.

Cumulative incidence of secondary outcomes: treatment (gray line), grade reclassification (gold line), and reclassification by grade or cancer extent (dashed blue line).

Fig 4.

Cumulative incidence of Gleason grade reclassification (GR) for men with very-low-risk prostate cancer (solid lines) and low-risk prostate cancer (dashed lines): all GR (blue), GR to 3 + 4 (gold), and GR to 4 + 3 and greater (gray).