Prostate cancer-specific mortality after biochemical recurrence in a cohort of US veterans
Posted Nov 04 2010 12:00am
A study reported this week in the Archives of Internal Medicine addresses the impact of biochemical recurrence on risk for prostate cancer-specific mortality (PCSM) among a cohort of more than 1,000 US veterans initially diagnosed and treated between 1991 and 1995.
Uchio et al. conducted their observational study in a community-based cohort of 1,313 prostate cancer patients who received treatment at nine Veterans Administration Medical Centers in New England. Medical records and death registry data were available for 1,270 of these men, and complete data for analysis of biochemical recurrence was available in 1,156 of the patients. All patients were eligible to receive further curative or palliative therapy as needed.
The three important outcome measures used in assessing the post-primary treatment progression of these patients were: biochemical progression after radical prostatectomy (defined as a PSA level of 0.4 ng/ml), biochemical progression (defined using the Phoenix criteria, i.e., the PSA nadir + 2 ng/ml), and prostate cancer-specific mortality (PCSM), determined through 2006.
Here is the authors’ breakdown of input data for the 1,156 patients for whom all relevant data were available:
231 patients (20.0 percent) underwent radical prostatectomy; 412 (35.6 percent) received radiation therapy; 200 (17.3 percent) received androgen deprivation therapy (ADT); and 313 (271. percent) received no primary therapy or watchful waiting.
The average (median) age of the patients was 70 years.
Most patients were white.
Comorbidity scores were none or mild in over 60 percent of the patients, and moderate to severe in 37 percent.
The average (median) PSA level at diagnosis was 8.9 ng/ml.
Nearly all of the patients (96 percent) were diagnosed with localized prostate cancer.
64 percent of the patients had moderate tumor differentiation.
Follow-up ranged between 11 and 16 years per patient.
The authors provide detailed outcome data for the 623 patients who were treated with radical prostatectomy (n = 225) and radiation therapy (n = 398). They do not (perhaps unfortunately) offer mortality data on the patients who received only ADT or watchful waiting.
For the patients initially treated with surgery:
5-, 10-, and 15-year rates of biochemical recurrence were 34, 37, and 37 percent respectively.
81 men died of their prostate cancer.
5-, 10-, and 15-year rates of PCSM were 3, 11, and 21 percent.
For the patients initially treated with radiation therapy:
5-, 10-, and 15-year rates of biochemical recurrence were 35, 46, and 48 percent respectively.
161 men died of their prostate cancer.
5-, 10-, and 15-year rates of PCSM were 11, 20 and 42 percent.
The authors first conclude that, “Biochemical recurrence is associated with increased prostate cancer mortality, yet when [biochemical recurrence] occurs only a minority of men subsequently die of their disease” (in this patient cohort).
What to make of these results?
Well the first and perhaps most important thing to recognize is that at 11-16 years of follow-up, 236/623 patients (37.9 percent) who received curative primary treatment were still alive. In other words the overall survival rate in the patients who received curative treatment was nearly 40 percent at up to 16 years of follow-up.
Second, it appears that the men who had surgery did better than the men who had radiation therapy but there are good reasons to suspect that the men receiving surgery were likely to be younger, have less advanced disease, and have fewer comorbidities than the men receiving radiation therapy, so we do not believe one can conclude from this study that surgery was “better” than radiation therapy.
Third, the risk for biochemical recurrence at 10 years or more after curative treatment is confirmed as being very low indeed.
Finally, even at 15 years of follow-up, among those who received curative treatment and then had a biochemical recurrence, less than half initially treated with radiation therapy (42 percent) and less than a quarter initially treated with surgery (21 percent) actually died of prostate cancer.
There has been increasing discussion as to just how clinically significant the traditional measures of biochemical recurrence really are. We have known for some time that many men who have biochemical recurrence can live for years with their disease without treatment and without any clinically significant impact on their lives. As usual, the hard thing is being able to differentiate accurately between these patients and the ones who really do need immediate (or at least early) second-line therapy. Uchio et al. add one more conclusion to their report, stating that, “New strategies for defining and managing treatment failure in prostate cancer are needed.” We would concur with that conclusion: biochemical failure alone is no longer good enough as a justification for immediate second-line therapy.