Abstract
BACKGROUND: Up to half of men with Gleason score 6 (GS6) prostate cancers initially managed with active surveillance (AS) will eventually require definitive therapy, usually due to tumor grade reclassification during follow-up. We examined the association between PTEN status on biopsy and subsequent clinicopathologic outcomes in men with GS6 cancers who enrolled in AS. METHODS: We performed a case-control study of men enrolled in the Johns Hopkins AS cohort with diagnostic biopsy tissue available for immunohistochemical (IHC) staining. IHC was performed for PTEN using genetically validated protocols for all patients. Cases included men who underwent grade reclassification to GS ≥ 3 + 4 = 7 on biopsy within 2 years of follow-up (i.e., early reclassification) or reclassification to GS ≥ 4 + 3 = 7 on biopsy or radical prostatectomy during follow-up (i.e., extreme reclassification). Control patients were diagnosed with GS6 cancer and monitored on AS for at least 8 years without undergoing biopsy reclassification. RESULTS: Among 67 cases with adequate tissue, 31 men underwent early reclassification and 36 men underwent extreme reclassification. Cases were compared to 65 control patients with adequate tissue for assessment. On initial prostate biopsy, cases were older (median age 67 vs. 65, p = 0.024) and were less likely to meet very-low-risk criteria (64 vs 79%, p = 0.042) as compared to controls. Although not statistically significant, PTEN loss was observed in only 1 (1.5%) of 65 controls as compared to 6 (9%) of 67 cases (p = 0.062). CONCLUSIONS: PTEN loss was rare among men with GS6 prostate cancer enrolled in AS at Johns Hopkins. Despite this, PTEN loss was more frequent among men who underwent early or extreme reclassification to higher-grade cancer as compared to controls. Additional studies in larger low-risk cohorts may better elucidate a potential role for PTEN in selecting patients for AS.