Researchers at the Department of Hematology-Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts performed an evaluation of the natural history of castration-resistant non-metastatic prostate cancer.
For their analysis, the researchers used data from 331 subjects in a placebo group of a randomized controlled trial to evaluate the relations of disease and host characteristics with time to first bone metastases (met) in men with prostate cancer, rising prostate-specific antigen (PSA) despite androgen deprivation therapy, and no radiographic evidence of metastases.
Relations between baseline covariates and clinical outcomes were also assessed by Cox proportional hazard analysis. The covariates evaluated were age, body mass index, prior prostatectomy, prior orchiectomy, Gleason score, performance status, PSA, urinary N-telopeptide, bone alkaline phosphatase, albumin, lactate dehydrogenase, and hemoglobin.
1- At 2 years, 46% of subjects had developed bone metastases, and 20% had died.
2- Median bone metastasis-free survival was 25 months.
3- In multivariate analysis, baseline PSA equal to greater than 13.1 ng/mL was associated with shorter overall time to first bone metastasis as well as bone metastasis-free survival.
4- PSA velocity was significantly associated with overall and bone metastasis-free survival.
5- Other covariates were not consistently associated with clinical outcomes.
6- In men with progressive castration-resistant prostate cancer and no detectable metastases, baseline PSA was significantly associated with time to first bone metastasis, bone metastasis-free survival, and overall survival.
7- Other disease and host characteristics, including body mass index and bone turnover markers, were not consistently associated with clinical outcomes.
So, what does this mean? The first stand out fact was that slightly under one half of men who did not have any signs of bone metastases when they became castrate resistant developed them within 2 years and as many as 20% of these men had died within the 2 year period. A PSA of over 13.1ng/ml predicted an earlier development of a bone met and overall , baseline PSA was predictive of a shorter survival time.
How can you possibly respond to this information? If you don’t have any evidence of a bone met once you have become castrate resistant it is vital to try and control your PSA quickly by 2nd line hormone deprivation methods.
Reference: Cancer. 2010 Nov 16. Epub ahead of print.
doi: 10.1002/cncr.25762; Smith MR, Cook R, Lee KA, Nelson JB.
Joel T Nowak, M.S.W.