BIOPSY OUTCOMES AND PATTERNS OF PROSTATE CANCER GRADE PROGRESSION IN THE PCM301 RANDOMIZED TRIAL OF VASCULAR TARGETED PHOTODYNAMIC THERAPY AND ACTIVE SURVEILLANCE: IMPLICATIONS FOR FOCAL THERAPY

INTRODUCTION AND OBJECTIVES: Post‐treatment biopsy findings are key endpoints for partial gland ablation (PGA) therapies including evaluation for presence of residual cancer, extent and grade that help to define surrogates of treatment success. We undertook a critical evaluation of longitudinal biopsy outcomes from the Phase 3 randomized trial of Vascular Targeted Photodynamic Therapy (VTP) vs. Active Surveillance (AS) to provide insight into site‐specific procedure related findings that have not previously been reported. METHODS: 413 men with ≤T2a Grade Group (GG) 1 cancers (≤3 positive cores, 3 to 5 mm cancer core length) were randomized to VTP PGA treatment (206 men) or AS (207 men). Scheduled per‐protocol biopsies were performed at 12 and 24 months and positive biopsy (Bx+) by site was recorded. Infield Bx+ (IBx+) includes all cancers found on follow up biopsy within the cancer bearing lobe identified as the index tumor at the time of diagnosis; Outfield Bx+ (OBx+) are those found within lobes initially negative at enrollment. GG≥2 Bx+ (Gleason score ≥ 3+4), considered a clinically meaningful finding, was evaluated separately. RESULTS: IBx+ was more common than OBx+, particularly in AS compared to VTP patients (61.8% vs 21.3%, respectively; p<0.01). The majority of IBx+ among AS patients was GG≥2 (56%). GG≥2 IBx+ was significantly lower in VTP men compared to AS (7.3% vs 34.8%; p<0.01). OBx+ occurred in a minority of VTP and untreated patients (16.5 vs 7.2%, respectively). GG≥2 OBx+ events were rare in either group (4.4% vs 2.9%, VTP vs AS, respectively). Completely Bxoutcomes were much higher in VTP treated men compared to AS (49% vs 13.5%, respectively; p<0.01). GG≥2 IBx+ occurred at a lower rate within 1 year for PGA men compared to AS (2.4% vs 17.4%, respectively; p <0.01). CONCLUSIONS: Increase in biopsy grade during AS occurs predominantly on the side of the index tumor in men with low‐risk unilateral cancers and is an event that can be significantly reduced with VTP ablation. The association of VTP treatment with decreased utilization of radical therapy strongly suggests short‐term clinical benefit associated with PGA therapy that will need to be confirmed with longerterm studies in validating biopsy outcomes as appropriate surrogate endpoints.