EXTERNAL-BEAM RADIOTHERAPY VERSUS RADICAL PROSTATECTOMY FOR CLINICAL STAGE T1-2 PROSTATE-CANCER - THERAPEUTIC IMPLICATIONS OF STRATIFICATION BY PRETREATMENT PSA LEVELS AND BIOPSY GLEASON SCORES

PURPOSE Prostate-specific antigen (PSA) has affected the management of prostate cancer by allowing better case selection. The comparison bet ween the two definitive treatment modalities, radiotherapy (RT) and ra dical prostatectomy (RP), can now be made accurately with respect to c ase selection and treatment outcome. PATIENTS AND METHODS The charts o f 787 patients with prostate carcinoma who were treated with either RP alone or RT alone between 1987 and 1993 were reviewed. Patients with stage T3 disease, without pretreatment PSA levels or biopsy Gleason sc ores (GS), with synchronous bladder cancers or receiving adjuvant ther apy, were excluded. Patients with less than 2 years' follow-up were al so excluded. Of the remaining 551 patients, 253 were treated with RT a nd 298 with RP. The median pretreatment PSA level for RP patients was 8.1 versus 12.1 for the RT patients. The median radiation dose was 68. 4 Gy. Positive margins were reported in 49% after RP. The median follo w-up time was 42 months (range: 24 to 108). RESULTS For the 551 patien ts, the 5-year biochemical relapse-free survival (bRFS) rate was 53%, with biochemical relapse being defined as either a detectable PSA leve l after RP, or two consecutive rising PSA levels after RT. All clinica l relapses were associated with rising PSA levels. The 5-year bRFS rat es for RT versus RP were 43% versus 57%, respectively. Multivariate ti me-to-failure analysis using the proportional hazards model for clinic al parameters showed pretreatment PSA level and biopsy Gleason scores to be the only independent predictors of relapse. Clinical stage and t reatment modality were not independent predictors of failure. Using PS A and GS, two risk groups were defined: low risk (PSA less than or equ al to 10.0 and GS less than or equal to 6) and high risk (PSA > 10.0 o r GS greater than or equal to 7). The 5-year RFS rates for the low-ver sus high-risk groups were 81% versus 34%, respectively Forty-eight per cent of RP patients were low-risk cases versus 33% of RT patients. The rate of surgical margin involvement in RP patients was 39% in the low -risk group versus 59% in the high-risk group. For low-risk patients, the 5-year RFS rates for patients treated with RT versus RP were 81% v ersus 80%, respectively. In this sub-group, the bRFS rates for patient s with negative margins were identical to the bRFS rates of patients t reated with radiotherapy. However, patients with positive surgical mar gins fared significantly worse. For high-risk patients, the 5-year RFS rates for patients treated with RT versus RP were 26% versus 37%, res pectively. In this subgroup, there was a definite advantage to surgery if negative margins were achieved: 5-year bRFS 62%, compared to 26% f or RT and 21% for surgery with positive margins. CONCLUSIONS By using biochemical failure as an endpoint, more failures are documented after RP or RT than previously suspected. However, case selection using pre treatment PSA levels and biopsy GS can result in large differences in control rates. Significantly more high-risk patients are treated with RT. By stratifying cases using PSA and biopsy GS, treatment outcome is equivalent after either radiotherapy or surgery. Further follow-up is needed to confirm these findings after 5 years. For low-risk cases, t here is no difference between radiotherapy and surgery, even when nega tive margins are achieved. Positive surgical margins predict for poor outcome even in low-risk cases. Standard radiotherapy alone should not be used for lesions with aggressive features. The outcome in high-ris k cases is better with surgery if negative margins are achieved. For s uch high-risk patients, several new treatment approaches are currently being investigated with either high-dose conformal radiotherapy with or without androgen blockade, or neoadjuvant androgen blockade or radi cal prostatectomy.