Continuing Maciejewski's debate on radiotherapy for locally advanced prostate cancer: I have even more dilemmas

Abstract

A recent critical review of clinical trials on radiotherapy for locally advanced prostate cancer by Maciejewski et al. [1] points to a conclusion that most of conventional 5-days-a-week, 2 Gy fraction regimes produce a “plateau effect”. Thus an increase in the total dose above approximately 70 Gy would not improve local tumour control, but could elevate the risk of later complications. Maciejewski et al. propose that radical hypofractionated 3D conformal or dose-intensity modulated radiotherapy with or without 3D HDR boost dose painting may improve the outcome of prostate radiotherapy. The present response describes some unforeseen challenges which may appear while implementing these new treatment strategies in clinical practice, and suggests possible solutions to solve these problems. Also, an alternative viewpoint on the data on dose-response in radiotherapy for prostate cancer is presented. It is postulated that, in addition to tumour hypoxia, distant metastases may create a quasi-plateau in dose-response, when biochemical failures and not loco-regional tumour control are used as the endpoint. Some arguments for the presence of dose response in postoperative EBRT for prostate cancer are presented. This some-what contradictory review of the existing data on radiotherapy for prostate cancer may be considered as a stimulus for further discussion regarding optimization of local therapy. It also illustrates an urgent need for new prospective trials, which would address the clinical and radiobiological ambiguities of theoretical predictions.