Overdetection of recurrence after radical prostatectomy: estimates based on patient and tumor characteristics

Abstract

Purpose: Prostate-specific antigen recurrence (PSA-R) after radical prostatectomy (RP) can occur years before metastasis. This study estimates the chance that an untreated PSA-R would not progress to clinical metastasis within the patient's lifetime, that is, that recurrence is overdetected.

Experimental design: Times from PSA-R to metastasis were estimated from patients with RP treated at Johns Hopkins University (Baltimore, MD) who did not receive salvage treatment (n = 441) at PSA-R. Times to other-cause death were based on U.S. life tables adjusted to reflect other-cause survival among RP cases in the Surveillance, Epidemiology, and End Results (SEER) registry. We used competing risks simulation to estimate lower bounds on the chance that other-cause death would precede clinical metastasis for patients with disease characteristics at diagnosis based on the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database (n = 4,455).

Results: Cumulative incidence of PSA-R in CaPSURE was 13.6% at 5 years and 19.9% at 10 years. The risk of other-cause death among patients with RP in SEER was 60% lower than the age-matched U.S. population. At least 9.1% of patients with PSA-R <5 years after RP and at least 15.6% of patients with PSA-R 5 to 10 years after RP were overdetected. At least 31.4% of patients over the age of 70 years at diagnosis, who recurred <10 years of diagnosis, were overdetected.

Conclusions: This analysis indicates that PSA-R after RP may be overdetected, with risk depending on patient age and tumor characteristics. The potential for overdetection of recurrence confirms the need for approaches to determine whether and when to initiate salvage therapies.

Figure 1

Schematic showing how the frequency of overdetection of recurrence may be estimated. Panel A is the survival curve for the time from PSA recurrence to metastasis in the absence of other-cause death. Panel B is the survival curve for the time from PSA recurrence to other-cause death. Overdiagnosis of PSA recurrence occurs when an individual dies of other causes before the point of metastasis and is represented by the smaller bar in Panel C. The computation of overdiagnosis of recurrence requires complete follow-up for metastasis and other-cause death; in practice we compute a lower bound on this quantity due to limited follow-up for metastasis.