BERKELEY, CA (UroToday.com) - ADT is no longer the sole treatment of advanced prostate cancer (PCa); other treatments including chemotherapy, vaccination and new hormonal treatments that do not lead to castration are already available or will be in the near future.
This suggests an increase in the number of management strategies where accurate determination of PCa prognosis will be all the more important. Many prognostic factors have already been reported and include factors reflecting PCa aggressivity before ADT initiation: Gleason score, PSA, tumor burden. However, one of the strongest predictors of survival seemed to be PSA nadir following ADT - the lower the nadir the better the survival. Data from the phase 3 SWOG Trial 9346 showed that PSA<4 ng/mL after 7 months of ADT was a powerful predictor of overall survival in metastatic PCa [J Clin Oncol. 2006;24:3984-3990]. Our study confirmed the prognostic value of PSA nadir that adds significant information to the PCa aggressivity criteria. Still the combination of these prognostic factors is not accurate enough.
More recently, the study from Choueiri and coworkers [Cancer 2009;115:981—7.] has shown for the first time that time to PSA nadir (TTN) following ADT was a significant predictive factor of overall survival (OS) in metastatic PCa. We have confirmed in our study the prognostic value of TTN regarding cancer-specific survival (CSS) and OS.
We have hypothesized that:
- TTN and PSA nadir could bring independent information, and
- that those two factors could be replaced by their ratio.
TTN and PSA nadir were indeed independent as regards CSS and OS in a multivariate analysis and we found that TTN/Nadir ratio brought independent information when analyzed concomitantly to TTN and PSA nadir. Moreover, if TTN/Nadir ratio was significantly associated with survival in the subgroup of patients with a PSA nadir <0.2 ng/mL, this was not the case for TTN as noted by Choueiri and coworkers. To better understand the prognostic performance of TTN/Nadir ratio compared to either TTN or PSA nadir alone, we looked at different scenarios that indeed corresponded to an array of prognosis that went from excellent: when TTN is long and PSA nadir is low, to poor; when TTN is short and PSA nadir remains high - with all the possible combinations in between.
The fact that the prognosis is all the better when PSA nadir is low corresponds to an intuitive notion. It was not the case for TTN where intriguingly, the longer it took to reach PSA nadir the better the prognosis was. To the best of our knowledge, there is no established pathophysiological explanation for this phenomenon. It is likely that in some way specifically linked to ADT, nadir is reached faster when PCa is aggressive and hence PSA resumes its rise earlier.
Because of the potential biases that a single-center, retrospective study could generate, we decided to validate the TTN/Nadir ratio by assessing its prognostic value in 2 additional independent databases from Oxford (Great Britain) and Seoul (Korea). The results were similar to the ones we obtained from the French set of patients and will be shortly submitted for publication.
Written by:
Jacques Irani, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
