Defining Failure of External—Beam RT for Prostate Cancer Is Challenging—Perhaps Impossible—Task

Field: Medicine (Health Sciences)

SALT LAKE CITY—Success may not come easily when treating prostate cancer with external-beam irradiation—but it is easier to recognize than failure: either long- or short-term, according to results of a multicenter study of 4,839 prostate cancer patients presented here at the ASTRO Annual Meeting. The problem, said principal investigator Deborah Kuban, MD, of the University of Texas M. D. Anderson Cancer Center in Houston, is that the treatment failure does not “fit” definitions used for surgical treatment. “Generally, the ASTRO definition, which is three consecutive PSA rises, underestimates outcome early on and then overestimates. The Houston definition, which is a PSA rise of at least 2 ng/ml above ‘cure’ nadir, [overestimates outcome] early on and then drops lower,” she said. Six Definitions Tested In the analysis six definitions were tested: (1) the ASTRO definition; (2) two PSA rises of at least 0.5 ng/ml each, backdated; (3) PSA at least 2 ng/ml above current nadir; (4) PSA at least 3 ng/ml above nadir; (5) PSA higher than 0.2 ng/ml; and (6) PSA higher than 0.5 ng/ml. All patients were treated with at least 60 Gy without androgen suppression from 1986 to 1995 at nine US institutions. Median follow-up was 6.3 years.Figure: Deborah Kuban, MD: “The problem is that the treatment failure does not ‘fit’ definitions used for surgical treatment. Generally, the ASTRO definition, which is three consecutive PSA rises, underestimates outcome early on and then overestimates. The Houston definition, which is a PSA rise of at least 2 ng/ml above ‘cure’ nadir, [overestimates outcome] early on and then drops lower.”For definitions 3–6, the failure date was recorded as the date the criterion was met, without backdating. Definitions 2, 3, and 4 were chosen because they were found in a previous analysis (by Howard Thames, PhD) to be both more sensitive and specific in predicting clinical outcome than the ASTRO definition, and definitions 5 and 6 have been proposed as a means to similarly compare surgical, brachytherapy, and external-beam treatment. The sensitivity for the ASTRO definition was 61% and specificity was 80%, while for definition 2 (Houston) the sensitivity was 68% and specificity 87%. For the other definitions sensitivity and specificity were as follows: definition 3, 74% and 82%; definition 4, 66% and 86%; definition 5, 91% and 9%; and definition six, 90% and 26%. Using the ASTRO definition 59% of patients had five-year PSA disease-free survival, while definitions 2, 3, and 4 estimated five-year PSA disease-free survival at 72%, 68%, and 72%, respectively. Second Paper from Same Group In a second paper from the same multicenter group, Eric Horwitz, MD, of Fox Chase Cancer Center, said the specificity and sensitivity of the ASTRO definition to predict distant failure was 55% and 68%. By contrast, definitions 2, 3, and 4 had specificity ranging from 69% (definition 2) to 76% (definition 3) and sensitivity in the 70% (definition 3) to 73% (definition 2) range. Dr. Horwitz concluded that the alternative definitions “potentially offer more accuracy in predicting who will remain free of cancer after treatment and who will truly develop metastatic disease based on a patient's post-treatment PSA levels. “The results of both papers add to a growing body of evidence that point to the need to modify the standard ASTRO definition to predict treatment failure.” Dueling Definitions? And while dueling definitions are clearly fodder for the research mills, Melvin Deutsch, MD, Professor of Radiation Oncology at the University of Pittsburgh, said that it might not matter in the world of clinical treatment. While dueling definitions are clearly fodder for the research mills, Melvin Deutsch, MD, Professor of Radiation Oncology at the University of Pittsburgh, said that it might not matter in the world of clinical treatment. He noted in an interview that everyone is trying to “fit” radiation into the box made by surgery: “After surgery, you have a PSA of 0,” he said. “So it is pretty easy to tell if it goes up that you have cancer somewhere still. “But with the prostate in place just irradiated, the PSA can go down to 0.4, 0.3, or 1 and then it can go down more or it can go up. But what are you going to do about it? A lot of men—especially older men—can live a long time even if their PSA goes up.” Dr. Deutsch said he is worried that a firm definition of failure could trigger “salvage therapy right away, when it might not be necessary. In any case I would not worry about older men. I think this is only a concern with younger men.”