In regards to Roach et al. defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: Recommendations of the RTOG–ASTRO Phoenix Consensus Conference (Int J Radiat Oncol Biol Phys 2006;65:965–974)

Abstract

I read with great interest the article by Roach et al. (1Roach M. Hanks G. Thames H.J. et al.Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference.Int J Radiat Oncol Biol Phys. 2006; 65: 965-974Abstract Full Text Full Text PDF PubMed Scopus (1975) Google Scholar). The panel’s recommendation is to use the Phoenix (previously also called the current nadir + 2) definition as a new standard to define biochemical failure (1Roach M. Hanks G. Thames H.J. et al.Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference.Int J Radiat Oncol Biol Phys. 2006; 65: 965-974Abstract Full Text Full Text PDF PubMed Scopus (1975) Google Scholar, 2Thames H. Kuban D. Levy L. et al.Comparison of alternative biochemical failure definitions based on clinical outcome in 4839 prostate cancer patients treated by external beam radiotherapy between 1986 and 1995.Int J Radiat Oncol Biol Phys. 2003; 57: 929-943Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar). The ASTRO definition is recommended to continue be used with strict adherence to guidelines. As the debate on the most appropriate definition of biochemical failure is settling, I would like to draw attention to how much impact this change of definition may have on the radiation dose–response analysis of prostate cancer. The position, the steepness, and time dependence of the dose–response curves can be very different for each risk group using the two definitions (3Cheung R. Tucker S.L. Lee A.K. et al.Dose-response characteristics of low- and intermediate-risk prostate cancer treated with external beam radiotherapy.Int J Radiat Oncol Biol Phys. 2005; 61: 993-1002Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 4Cheung R. Tucker S.L. Lee A.L. et al.Assessing the impact of an alternative biochemical failure definition on radiation dose response for high-risk prostate cancer treated with external beam radiotherapy.Int J Radiat Oncol Biol Phys. 2005; 61: 14-19Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar) for the intermediate-risk patients. For example, the Phoenix definition projected much smaller benefit for further dose escalation beyond 78 Gy than when the ASTRO definition was used (3Cheung R. Tucker S.L. Lee A.K. et al.Dose-response characteristics of low- and intermediate-risk prostate cancer treated with external beam radiotherapy.Int J Radiat Oncol Biol Phys. 2005; 61: 993-1002Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). For the high-risk group, TD50, the dose to achieve 50% tumor control, increased from 70.4 Gy using the Phoenix definition to 75.5 Gy using the ASTRO definition (4Cheung R. Tucker S.L. Lee A.L. et al.Assessing the impact of an alternative biochemical failure definition on radiation dose response for high-risk prostate cancer treated with external beam radiotherapy.Int J Radiat Oncol Biol Phys. 2005; 61: 14-19Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar). As we are still searching for the optimal dose to treat our prostate cancer patients, accurate dose–response modeling is important to project benefit of further dose escalation. Furthermore, the interest on using hypofractionation to treat prostate cancer has surged since Brenner and Hall published a lower-than-expected α/β ratio for prostate cancer (5Brenner D.J. Hall E.J. Fractionation and protraction for radiotherapy of prostate carcinoma.Int J Radiat Oncol Biol Phys. 1999; 43: 1095-1101Abstract Full Text Full Text PDF PubMed Scopus (780) Google Scholar). It should be noted that the steepness of the dose–response curve could also have an impact on the estimation of the α/β ratio of prostate cancer (6Bentzen S.M. Ritter M.A. The alpha/beta ratio for prostate cancer: what is it, really?.Radiother Oncol. 2005; 76: 1-3Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar). In reply to Dr. CheungInternational Journal of Radiation Oncology, Biology, PhysicsVol. 66Issue 4PreviewDr. Cheung is absolutely correct. Using the so-called “Phoenix” definition (defined as nadir + 2 ng/mL) significantly changes the biochemical failure pattern compared with using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition (1). In addition to his retrospective studies, at least one Phase III randomized trial demonstrated that the use of the Phoenix definition could have an impact on the interpretation of dose–response data (2–4). In the Dutch trial reported by Peeters et al. Full-Text PDF