Radiation failure and surgical failure criteria don’t match up in treatment of localized prostate cancer
Posted Sep 28 2008 7:03pm
It appears that the American Society for Therapeutic Radiation Oncology (ASTRO)’s criteria for radiation failure may be significantly less rigorous than the criteria used by Walsh and his colleagues at Johns Hopkins (and by most other surgeons) to define surgical failure of treatment for localized prostate cancer.
Given the absence of randomized trials of radiotherapy (RT) vs. radical prostatectomy (RP) in treatment of localized disease, there is no good means to compare outcomes of these very different treatment methods.
Biochemical failure after RP is defined as an initial PSA level ≥ 0.2 ng/mL, followed by a confirmatory PSA of ≥ 0.2 ng/ml. In 2005 ASTRO defined failure after RT as a PSA value of 2 ng/mL greater than the lowest PSA level noted (the “nadir” PSA level). Nielsen and colleagues at Johns Hopkins have now sought to compare these criteria by applying the ASTRO failure criteria to their RP series of 2,570 patients, all treated by a single surgeon between 1986 and 2004.
The authors applied the PSA nadir + 2 definition to their series by defining biochemical failure as a postoperative PSA level of ≥ 2 ng/mL, i.e., they assumed that the “nadir” PSA level was zero, the best-case scenario. They then compared the two different failure criteria by calculating the probabilities of biochemical recurrence-free survival (BRFS) for the group using the ≥ 0.2 ng/mL cut-off point for surgery and 2 ng/mL for radiotherapy. Their results can be summarized as follows:
The N+2 definition of failure (i.e., 2 ng/mL) significantly overestimated the BRFS in this study relative to the ≥ 0.2 ng/mL definition. Using the ≥ 0.2 ng/mL definition, the BRFS estimates at 5, 10, 15 years were 88.6, 81.2, and 78.1 percent, respectively. The corresponding percentages for the N+2 definition were 94.6, 89.4, and 84.3 percent.
For 322 patients with a post-surgery PSA level of ≥ 0.2 ng/mL, the median time to biochemical recurrence was 2.8 years based on the ≥ 0.2 ng/mL definition as compared to 7.9 years for the N+2 definition.
The N+2 definition resulted in a highly significant delay in the determination of failure, relative to the 0.2 ng/mL definition.
Now the validity of this method of comparing the two sets of failure criteria in this manner is obviously open to question, and is unlikely to be accepted by the radiotherapy community. However, it is clear that if one simply correlates biochemical failure to clinical failure, the current ASTRO N+2 definition significantly overestimates BRFS for local and for distant disease recurrence. At 5 years, the N+2 definition overestimated the BRFS by 52 percent among patients with a clinical local recurrence and by 17 percent among those with a metastatic recurrence.