Long-Term Outcomes in Patients Using Protocol-Directed Active Surveillance for Prostate Cancer

Abstract

Importance: Outcomes from protocol-directed active surveillance for favorable-risk prostate cancers are needed to support decision-making.

Objective: To characterize the long-term oncological outcomes of patients receiving active surveillance in a multicenter, protocol-directed cohort.

Design, setting, and participants: The Canary Prostate Active Surveillance Study (PASS) is a prospective cohort study initiated in 2008. A cohort of 2155 men with favorable-risk prostate cancer and no prior treatment were enrolled at 10 North American centers through August 2022.

Exposure: Active surveillance for prostate cancer.

Main outcomes and measures: Cumulative incidence of biopsy grade reclassification, treatment, metastasis, prostate cancer mortality, overall mortality, and recurrence after treatment in patients treated after the first or subsequent surveillance biopsies.

Results: Among 2155 patients with localized prostate cancer, the median follow-up was 7.2 years, median age was 63 years, 83% were White, 7% were Black, 90% were diagnosed with grade group 1 cancer, and median prostate-specific antigen (PSA) was 5.2 ng/mL. Ten years after diagnosis, the incidence of biopsy grade reclassification and treatment were 43% (95% CI, 40%-45%) and 49% (95% CI, 47%-52%), respectively. There were 425 and 396 patients treated after confirmatory or subsequent surveillance biopsies (median of 1.5 and 4.6 years after diagnosis, respectively) and the 5-year rates of recurrence were 11% (95% CI, 7%-15%) and 8% (95% CI, 5%-11%), respectively. Progression to metastatic cancer occurred in 21 participants and there were 3 prostate cancer-related deaths. The estimated rates of metastasis or prostate cancer-specific mortality at 10 years after diagnosis were 1.4% (95% CI, 0.7%-2%) and 0.1% (95% CI, 0%-0.4%), respectively; overall mortality in the same time period was 5.1% (95% CI, 3.8%-6.4%).

Conclusions and relevance: In this study, 10 years after diagnosis, 49% of men remained free of progression or treatment, less than 2% developed metastatic disease, and less than 1% died of their disease. Later progression and treatment during surveillance were not associated with worse outcomes. These results demonstrate active surveillance as an effective management strategy for patients diagnosed with favorable-risk prostate cancer.

Figure 1.. Occurrence of Biopsy Reclassification and Treatment Among Canary PASS Participants

ADT indicates androgen deprivation therapy; PASS, Prostate Active Surveillance Study; RP, radical prostatectomy. Participants treated after the confirmatory biopsy (n = 425); participants treated after subsequent surveillance biopsy (n = 325); participants treated before surveillance biopsy (n = 49).

Figure 2.. Cumulative Incidence Curves for Outcomes During Active Surveillance

The curves for each end point were calculated separately and superimposed. The median time of observation from diagnosis for each outcome in the full cohort (N = 2155) (A and B) and in the subcohort enrolled after diagnosis and before confirmatory biopsy (n = 1403) (C and D), respectively, were: treatment, 6.3 years (IQR, 3.5-11) and 5.6 years (IQR, 3.5-9.7); any reclassification, 6.1 years (IQR, 3.5-11) and 5.5 years (IQR, 3.5-9.4); extreme reclassification, 6.3 years (IQR, 3.6-11), and 5.6 years (IQR, 3.5-9.7); all-cause mortality, 7.1 years (IQR, 4.2-11) and 6.6 years (IQR, 4-10); metastasis, 7.2 years (IQR, 4.2-11) and 6.7 years (IQR, 4-10); and prostate cancer–specific mortality, 7.2 years (IQR, 4.2-11) and 6.7 years (IQR, 4-10).

Figure 3.. Timelines From Cancer Diagnosis for Individual Participants Sorted First by Status at Last Contact and Then by Time Receiving Active Surveillance

GG indicates grade group; PSA, prostate-specific antigen; RP, radical prostatectomy. Panel B is an inset of participants in panel A who had recurrence after treatment; panel C is an inset of participants in panel A who developed metastasis.