Radiation Therapy for Clinically Localized Prostate Cancer: A Multi-Institutional Pooled Analysis

Reviewers: John Han-Chih Chang, MD
Source: JAMA 1999; Volume 281: pages 1598 - 1604.

AbstractContext Prostate-specific antigen (PSA) evaluation leads to the early detection of both prostate cancer and recurrencesfollowing primary treatment. Prostate-specific antigen outcome information on patients 5 or more years following treatmentis limited and available mainly as single-institution reports.

Objectives To assess the likelihood and durability of tumor control using PSA evaluation 5 or more years after radicalexternal beam radiation therapy and to identify pretreatment prognostic factors in men with early prostate cancer treatedsince 1988, the PSA era.

Design and Setting Retrospective, nonrandomized, multi-institutional pooled analysis of patients treated with externalbeam radiation therapy alone between 1988 and 1995 at 6 US medical centers. Follow-up lasted up to a maximum of 9 years.Outcome data were analyzed using Cox regression and recursive partitioning techniques.

Patients A total of 1765 men with stage T1b, T1c, and T2 tumors treated between 1988 and 1995 with external beamradiation. The majority (58%) of patients were older than 70 years and 24.2% had initial PSA values of 20 ng/mL or higher.A minimum of 2 years of subsequent follow-up was required for participation.

Main Outcome Measure Actuarial estimates of freedom from biochemical failure.

Results The 5-year estimates of overall survival, disease-specific survival, and the freedom from biochemical failure are85.0% (95% confidence interval [CI], 82.5%-87.6%), 95.1% (95% CI, 94.0%-96.2%), and 65.8% (95% CI, 62.8%-68.0%),respectively. The PSA failure-free rates 5 and 7 years after treatment for patients presenting with a PSA of less than 10ng/mL were 77.8% (95% CI, 74.5%-81.3%), and 72.9% (95% CI, 67.9%-78.2%). Recursive partitioning analysis of initial PSAlevel, palpation stage, and the Gleason score groupings yielded 4 separate prognostic groups: group 1, included patientswith a PSA level of less than 9.2 ng/mL; group 2, PSA level of at least 9.2 but less than 19.7 ng/mL; group 3, PSA level atleast 19.7 ng/mL and a Gleason score of 2 to 6; and group 4, PSA level of at least 19.7 ng/mL and a Gleason score of 7 to 10.The estimated rates of survival free of biochemical failure at 5 years are 81% for group 1, 69% for group 2, 47% for group 3,and 29% for group 4. Of the 302 patients followed up beyond 5 years who were free of biochemical disease, 5.0% relapsedfrom the fifth to the eighth year.

Conclusions Estimated PSA control rates in this pooled analysis are similar to those of single institutions. These ratesindicate the probability of success for subsets of patients with tumors of several prognostic category groupings. Theseresults represent a multi-institutional benchmark for evidence-based counseling of prostate cancer patients about radiationtreatment.Discussion and CritiqueThis was a very heterogeneous group in many respects. Most were T2 (palpable localized) lesions. The range of PSA's was 0.2 - 2028 with a median of 10.1. Most of the patients were treated with an external beam 4-field technique with dosesof 1.8 - .1 per day to a total dose of 63 - 79 Gy. The prescription points of the various institutions were not specified. Thepatient characteristics were listed in table 1. Treatment institutions were the following: University of Michigan, Fox ChaseCancer Center, Massachusetts General Hospital, Washington University, Eastern Virginia Medical School and StanfordUniversity Medical Center.

The endpoint utilized was 5-year biochemical NED (bNED or no evidence of disease on the basis of the PSA value). Toarrive at the 4 groupings listed in the abstract, the authors compared the numerous characteristics listed in table 2. Theyfound no difference in bNED among patients who had initial PSA's less than 10. These patients with low PSA didsignificantly better that those with PSA's of 10 to less than 20, who did significantly better than those with PSA's above20. Tumor (T) stage of the primary lesion was only significant in univariate analysis, but when stratified for initial PSA andgleason score, it was not statistically significant. The gleason score stratification broke down to those that had 2 - 6 had abetter 5-year bNED survival than those with 7 or more. Again this is all nicely summarized in table 2.

Essentially, as the authors have described this is a way to stratify patient into categories so that the cancer physician maydetermine the chance of the patient remaining bNED at 5 years. The major and perhaps the only significant criticism is therelatively short follow-up, the median being 4.1 years. Though the claim is that only 5% fail after 5 years in the 300 or sothat have made it out beyond 5 years, it is not a number that can be completely relied upon given the entire studypopulation size (over 1700). Overall, the 4 grouping system to predict biochemical outcome seems to be a relatively fairguide. Longer follow-up may decrease our optimism for the more favorable groups, though I doubt it will change thegroupings.