Outcomes of Active Surveillance for Clinically Localized Prostate Cancer in the Prospective, Multi-Institutional Canary PASS Cohort

Abstract

Purpose: Active surveillance represents a strategy to address the overtreatment of prostate cancer, yet uncertainty regarding individual patient outcomes remains a concern. We evaluated outcomes in a prospective multicenter study of active surveillance.

Materials and methods: We studied 905 men in the prospective Canary PASS enrolled between 2008 and 2013. We collected clinical data at study entry and at prespecified intervals, and determined associations with adverse reclassification, defined as increased Gleason grade or greater cancer volume on followup biopsy. We also evaluated the relationships of clinical parameters with pathology findings in participants who underwent surgery after a period of active surveillance.

Results: At a median followup of 28 months 24% of participants experienced adverse reclassification, of whom 53% underwent treatment while 31% continued on active surveillance. Overall 19% of participants received treatment, 68% with adverse reclassification, while 32% opted for treatment without disease reclassification. In multivariate Cox proportional hazards modeling the percent of biopsy cores with cancer, body mass index and prostate specific antigen density were associated with adverse reclassification (p=0.01, 0.04, 0.04, respectively). Of 103 participants subsequently treated with radical prostatectomy 34% had adverse pathology, defined as primary pattern 4-5 or nonorgan confined disease, including 2 with positive lymph nodes, with no significant relationship between risk category at diagnosis and findings at surgery (p=0.76).

Conclusions: Most men remain on active surveillance at 5 years without adverse reclassification or adverse pathology at surgery. However, clinical factors had only a modest association with disease reclassification, supporting the need for approaches that improve the prediction of this outcome.

Keywords: prospective studies; prostatic neoplasms; watchful waiting.

Figure 1. Status of PASS participants

Participants are grouped according to whether they experienced adverse reclassification (an increase in biopsy Gleason grade and/or ratio of number of cores containing cancer to total number of cores from <34% to ≥34%) or had no reclassification. Participants with no reclassification are further divided into participants who had at least one repeat biopsy, and thus able to be reclassified, and those who had not yet had a repeat biopsy, and thus not able to be reclassified. Participants are further divided into those that are active (continuing to use active surveillance), had documented treatment, or inactive (left the study with no documentation of treatment).

Figure 2. Kaplan-Meier estimates of survival free of outcome

Outcomes are a.) any increase in biopsy Gleason score (grade reclassification); b.) either an increase in biopsy Gleason score or volume to ≥34% of cores with cancer (grade/volume reclassification), c.) treatment. Time zero was defined as the time of diagnosis. Participants without event were censored at the date of last study contact.