FLOW CYTOMETRIC ANALYSIS OF DNA-PLOIDY, PERCENT S-PHASE FRACTION, ANDTOTAL PROLIFERATIVE FRACTION AS PROGNOSTIC INDICATORS OF LOCAL-CONTROL AND SURVIVAL FOLLOWING RADIATION-THERAPY FOR PROSTATE CARCINOMA

Purpose: Treatment recommendations for localized prostate cancer may b e improved by the identification of tumor factors prognostic for local control and survival. In this retrospective study, flow cytometric de oxyribonucleic acid (DNA) ploidy analysis and cell cycle analysis were performed on paraffin-embedded biopsy material to determine if additi onal prognostic factors could be identified in patients treated with r adiation therapy. Methods and Materials: Seventy patients with T1-4NxM 0 tumors were identified in whom the primary treatment had been radica l radiation therapy with no prior or concurrent endocrine therapy and in whom sufficient prostatic tissue was available for flow cytometric analysis. There were 40 diploid, 26 aneuploid, and 4 multiploid cases. Aneuploid and multiploid cases were combined for analysis. Cell cycle data were obtained on all diploid and 10 aneuploid cases. Results: Th e histologic differentiation of the tumor (well or moderate vs. poor) was an independent predictor of overall survival and disease-free surv ival (p = 0.05 and 0.01, respectively). Local control was worse in the poorly differentiated patients, although this was not statistically s ignificant in a multivariate analysis (p = 0.08). Neither T-stage, deo xyribonucleic acid ploidy (diploid vs. nondiploid), percent S-phase fr action, nor total proliferative fraction (S-phase fraction + G(2)M) si gnificantly predicted for any of these endpoints. Within the diploid a nd well or moderately differentiated subgroup (n = 25), S-phase (< 4.2 vs. greater than or equal to 4.2) was a significant predictor of loca l control (100% vs. 51%, p = 0.03). A comparable distinction could be made using total proliferative fraction (< 10% vs. greater than or equ al to 10%) with local control rates of 100% vs. 56% (p = 0.05). Among the poorly differentiated tumors, no similarly favorable subgroup was identified. Conclusions: This retrospective and multivariate analysis identifies both histology and percent S-phase or total proliferative f raction as predictors of local control following irradiation, and conf irms that histology, but not DNA ploidy, is significant for overall su rvival. If these previously unreported findings are confirmed by prosp ective studies, S-phase should be added to histology as a parameter in the evaluation of clinical trials.