835 E D I T O R I A L Predicting Outcomes of Therapy for Prostate Carcinoma Patients Michael K. Brawer, M.D. Northwest Prostate Institute, Seattle, Washington. G See referenced original article on pages 971– 6, this issue. Address for reprints: Michael K. Brawer, M.D., Northwest Prostate Institute, Seattle, WA 98133. Received March 17, 1998; accepted March 24, 1998. © 1998 American Cancer Society reen et al., the authors of an article published in this issue of Cancer, are to be congratulated for providing yet another important study demonstrating the prognostic significance of the Gleason score in predicting failure in the treatment of clinically localized prostate carcinoma. The investigation involved 563 men undergoing definitive external beam radiation therapy for clinically localized T1–T3, N0 or NX, M0 carcinoma. The authors demonstrated that patients with a Gleason score of 7 or higher on diagnostic biopsy have a significantly higher rate of failure as determined by prostate specific antigen (PSA) progression. This finding supports other radiation therapy series1,2 as well as many radical prostatectomy experiences.3,4 Certainly there are some potential limitations in this investigation. Apparently no reference pathology was utilized to establish uniformity in assignment of grade. The patients comprised a relatively high risk cohort (more than half of the men had a pretherapy PSA level greater than 10.0 ng/mL). The overall findings, however, clearly demonstrate that a Gleason score of 7 is a significant predictor of monotherapy failure and supports the belief of many that men with a Gleason score of 7 or higher should receive neoadjuvant or adjuvant hormonal therapy, or other combination therapies. It is a true tribute to Dr. Donald F. Gleason that his grading system remains the most important predictor of success or failure in the treatment of clinically localized prostate carcinoma.5 Of course, what remains enigmatic is the identification of those factors associated with the architectural features evident in high grade carcinoma that give rise to dissemination of disease or perhaps make the neoplasm less responsive to locally directed therapy. Clearly, investigative efforts should attempt elucidation of the pathogenic mechanisms associated with high grade disease. Prostate carcinoma patients and their families, the clinicians who treat these patients, and investigators of this disease are all clamoring for the development of novel prognostic and staging markers. This subject was a major theme of a recent consensus meeting, the proceedings of which were published in Cancer.6,7 Significant limitations exist for the establishment of clinically useful markers in prostate carcinoma. These include a tremendous degree of tumor heterogeneity, the degree of which is perhaps unique among all common malignancies. This requires prognostic markers to be either uniformly expressed throughout the neoplasm, and thus a amenable to identification in limited tissue sampling (such as that afforded by needle 836 CANCER September 1, 1998 / Volume 83 / Number 5 biopsy), or systemically expressed. Development of such markers will allow increased stratification of the malignant potential of a given patient’s neoplasm and perhaps allow tailoring of therapy to that patient. Until such factors are well established, the histologic carcinoma pattern represented by a Gleason score of 7 or higher will provide useful information with which we may counsel our patients. 3. 4. 5. REFERENCES 1. 2. Bagshaw MA, Cox RS, Ramback JE. Radiation therapy for localized prostate cancer: justification of long-term followup. Urol Clin North Am 1990;17:787– 802. Zagars GK, Ayala AG, von Eschenbach AC, Pollack A. The prognostic importance of Gleason grade in prostatic adenocarcinoma: a long-term follow-up study of 648 patients 6. 7. treated with radiation therapy. Int J Radiat Oncol Biol Phys 1995;31:237– 45. Epstein JI, Partin AW, Sauvageot J, Walsh PC. Prediction of progression following radical prostatectomy: a multivariate analysis of 721 men with long-term follow-up. Am J Surg Pathol 1996;20:286 –92. Epstein JI, Pizov G, Walsh PC. Correlation of pathologic findings with progression after radical retropubic prostatectomy. Cancer 1993;71:3582–93. Gleason DF. Histologic grading of prostate cancer: a perspective. Hum Pathol 1992;23:273–9. Hutter RVP, Montie JE, Busch C, et al. Current prognostic factors and their relevance to staging. Cancer 1996;78:369 –70. von Eschenbach AC, Brawer MK, di Sant’Agnese PA, et al. Exploration of new pathologic factors in terms of potential for prognostic significance and future applications. Cancer 1996;78:372–5.