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Sources of Funding: None

Introduction

The prognostic heterogeneity in patients with Gleason Score (GS) 7 prostate cancer (PC) is owed to the more aggressive behavior of GS 4+3 vs. 3+4 disease. Modifications in the Gleason grading system were proposed to address these differences in cancer behaviors when reporting GS 7 PC, as Grade Group 3 portends a higher likelihood of systemic spread compared to Grade Group 2. Prognostic differences are recognized in patients undergoing surgical extirpation; we therefore sought to investigate differences in outcomes between Groups 2 and 3 patients treated with radiotherapy with or without hormone therapy (HT).

Methods

A retrospective analysis was performed on a prospectively maintained database of patients receiving brachytherapy ± external beam radiation therapy ± hormone therapy (HT) for NCCN low, intermediate or high-risk PC at a single institution between 1990-2011. Patients with a minimum follow-up of 5 years were included. Kaplan-Meier survival analyses were used to compare GS 3+4 vs 4+3 for the study endpoints of biochemical recurrence (BCR; Phoenix criteria), distant metastases, and cancer specific survival (CSS), with and without stratification by biological effective dose (BED; <150 vs. 150-200 vs. >200 Gy). Cox proportional hazards model was used to assess risk of BCR over time, adjusting for HT receipt, GS, stage, PSA, and BED.

Results

472 patients were identified with GS 7 PC; 276 with GS 3+4 and 196 patients with GS 4+3. No significant differences were seen in BCR (p=0.349), distant metastasis (p=0.07), and CSS (p=0.62) in GS 3+4 vs. 4+3. Among patients with PSA > 10 ng/ml or stage > T2b, significant differences in biochemical freedom from failure (BFFF) were observed for GS 3+4 vs. 4+3 stratified by escalating BED (table 1). Neoadjuvant HT improved 10-year BFFF from 81.3% to 88.2% for GS 3+4 and from 66.3% to 87.6% for GS 4+3 (p=0.021). Cox proportional hazards model demonstrated HT receipt (HR 11.86, 95% CI 1.26 – 112.06, p=0.031) and total BED (HR 0.98, 95% CI 0.97 – 0.99, p=0.001) significantly impact time to BCR.

Conclusions

BCR, distant metastasis, and CSS were similar between patients in Group 2 and 3 PC treated with radiotherapy. Higher BED substantially improves BFFF in higher risk patients with PSA >10 and stage > T2b, especially in Group 3. Higher dose and neoadjuvant HT should be strongly considered in GS 7 PC with adverse features.

Funding

None