Dr Zaorsky said clinicians urgently need a better detection method than the PSA test to determine how patients are progressing and for determining which patients may be at risk for metastasis.

“Future clinical trials should not be powered solely to detect a difference in PSA outcomes,” Dr Zaorsky told Cancer Therapy Advisor. “Genomics and novel imaging modalities, for example multiparametric magnetic resonance imaging, will likely be tests used in the future to detect recurrence.”

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Mark Garzotto, MD, who is an associate professor of urology and radiation medicine at Oregon Health & Science University and director urologic oncology, Portland VA Medical Center in Portland, OR, said the authors performed a thorough analysis of the available data. However, he said there are some important limitations that affect the ability to interpret the results.

“The main issue is the short follow-up of many of the trials in the meta-analysis, several of which had only about a 5-year median follow-up. We know that from the Johns Hopkins series of surgically treated patients that the median time to metastases is about 8 years.After PSA-recurrence, death is about 5 years after this event. Thus, in order to capture the most clinically significant events in localized prostate cancer, we really need a minimum of 15 years follow-up from the time of treatment. Unfortunately, the studies collated for this analysis do not have the power to detect these clinically significant events,” Dr Garzotto told Cancer Therapy Advisor.

He said from this study it is fair to say that PSA testing is not very useful to detect outcomes from radiation in the intermediate-term. However, Dr Garzotto said for long-term events more study is warranted.

Urologist Gopal Gupta, MD, who is with Loyola University in Chicago, IL, agreed with Dr Garzotto. He said it is important that clinicians rethink what PSA progression means as a study endpoint in a clinical trial.

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“This phenomenon of obtaining an improvement in biochemical recurrence (by using PSA failure definitions) but with no effect on overall survival is common in clinical trials for prostate cancer therapies,” Dr Gupta told Cancer Therapy Advisor. “Ultimately, the real end point we need to make progress towards is overall survival. PSA is still the tool we use to mark response to therapy regardless treatment modality. The real lesson is to set the endpoint for clinical trials not to PSA progression, but to overall survival or distant metastasis benefit.”


  1. Zaorsky NG, Keith SW, Shaikh T, et al. Impact of radiation therapy dose escalation on prostate cancer outcomes and toxicities [published online ahead of print March 24, 2016]. Am J Clin Oncol. doi: not available.
  2. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281(17):1591-1597.