Optimal radiotherapy for prostate cancer: Predictions for conventional external beam, IMRT, and brachytherapy from radiobiologic models

Purpose: To determine, on the basis of radiobiological models, optimal moda lities of radiotherapy for localized prostate cancer, and to provide a rati onal basis for therapeutic decisions. Methods and Materials: An algorithm based on extensions to the linear-quadr atic (LQ) cell survival model is constructed for fractionated and protracte d irradiation. These radiobiological models include prostate tumor cell lin e-derived LQ parameters, clonogen repopulation, repair of sublethal damage, hypoxia, and radioisotope decay, In addition, dose inhomogeneities for bot h IMRT and brachytherapy (I-125 and Pd-103) from patient-derived Dose Volum e Histograms (DVH), as well as dose escalation, are incorporated. Three ris k groups are defined in terms of sets of biologic parameters tailored to co rrespond to clinical risk groups as follows: Favorable-iPSA < 10 and bGS le ss than or equal to 6 and stage T2; Intermediate-one parameter increased; a nd Unfavorable-two or more parameters increased. Tumor control probabilitie s (TCP) are predicted for conventional external beam radiotherapy (EBRT, in cluding 3D-CRT), intensity modulated radiotherapy (IMRT), and permanent bra chytherapy, Results: Brachytherapy is less susceptible to variations in alpha/beta than EBRT and more susceptible to variations in clonogen potential doubling tim e (T-p), Our models predict TCP consistent with the bNED results from recen t dose escalation trials and long-term outcomes from brachytherapy, TCP fro m IMRT are systematically superior to those from conventional fractionated RT, and suggests its possible use in dose escalation without additional dos e to surrounding normal tissues. For potentially rapidly dividing tumors (T -p < 30 days) Pd-103 yields superior cell kill compared with I-125, but for very slowly proliferating tumors the converse is suggested. Brachytherapy predicts equivalent or superior TCP to dose escalated EBRT, For unfavorable risk tumors, combined 45 Gy EBRT+brachytherapy boost predicts superior TCP than with either modality alone. Conclusions: The radiobiological models presented suggest a rational basis for choosing among several radiotherapeutic modalities based on biologic ri sk factors. In addition, they suggest that IMRT may potentially be superior to 3D-CRT in allowing dose escalation without increased morbidity, and tha t brachytherapy, as monotherapy or as boost, may achieve superior tumor con trol compared with dose escalation 3D-CRT, The latter conclusion is support ed by clinical data. (C) 2000 Elsevier Science Inc.