Factors Associated with Time to Conversion from Active Surveillance to Treatment for Prostate Cancer in a Multi-Institutional Cohort

Abstract

Purpose: We examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer.

Materials and methods: A multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses.

Results: Of 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36-1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29-2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11-1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41-1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19-5.96) and number of cancerous biopsy cores (3 vs 1-2 cores aHR 1.59, 95% CI 1.37-1.84; ≥4 vs 1-2 cores aHR 3.29, 95% CI 2.94-3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93-0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry.

Conclusions: A shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.

Keywords: human genetics; prostatic neoplasms; race factors; watchful waiting.

Figure 1.

Scaled Venn diagram shows reason for conversion to treatment including grade reclassification, tumor volume progression and/or PSA progression (a), and anxiety alone without other reasons (b). Percentages are out of total number of men who converted (2,260). Overlap between anxiety with other reasons for conversion: grade reclassification, 5 (0.2%); tumor volume progression, 0; PSA progression, 6 (0.3%).

Figure 2.

Kaplan-Meier analysis of time to conversion to treatment by patient demographic and cancer clinical factors. A, Kaplan-Meier plots of prostate cancer clinical variables in relation to time to conversion. P value is reported from log-rank test. B, Kaplan-Meier plots of race, genetic ancestry and family history of prostate cancer in relation to time to conversion. P value is reported from log-rank test. CFP, conversion-free probability.