We are in desperate need of validated biomarkers, which can serve as surrogates for survival. Currently, our doctors must make decisions about which drugs to use and how long to stay on these drugs without any scientific backup or consensus driven direction to their decisions.

Our clinical trials for evaluating survival of potential new advanced prostate cancer treatments could be completed more quickly if we had survival biomarkers. Instead of waiting for men to die we could instead project mortality and be able to evaluate an investigational drugs efficacy. The time has come to make a major effort to develop these biomarkers.

Circulating Tumor Cells (CTC) has been seriously considered to be one potential biomarker. They hold a lot of promise and seem to respond to all the above concerns.

Not often discussed, but examining CTCs alone and in combination with other biomarkers as a surrogate for overall survival was a secondary objective of COU-AA-301, a multinational, randomized, double-blind phase III trial of abiraterone acetate (Zytiga) plus prednisone versus prednisone alone. The biomarkers were measured at baseline and 4, 8, and 12 weeks, with 12 weeks being the primary measure of interest.

A biomarker panel using CTC count and lactate dehydrogenase (LDH) level made it to the twelve-week mark and the researchers were able to gather surrogate biomarker data from 711 men.

The abiraterone acetate plus prednisone and prednisone-alone groups demonstrated a significant survival difference
(P = .034); surrogate distribution at 12 weeks differed by treatment (P < .001); the discriminatory power of the surrogate to predict mortality was high (weighted c-index, 0.81); and adding the surrogate to the model eliminated the treatment effect on survival.Overall, 2-year survival of men with CTCs < 5 (low risk) versus patients with CTCs ? 5 cells/7.5 mL of blood and LDH > 250 U/L (high risk) at 12 weeks was 46% and 2%, respectively.

This trial demonstrated and confirmed that a biomarker panel containing CTC number and LDH level could be an excellent surrogate for survival at the individual-patient level in men with metastatic castrate resistant prostate cancer (mCRPC).


Joel T. Nowak, M.A., M.S.W.