Low PSA predicts poor prognosis in high-grade prostate cancer

Washington-In men with high-grade prostate cancer, outcomes after radical prostatectomy are generally poorest for those with a low preoperative PSA (<2.5 ng/mL), say researchers from Northwestern University Feinberg School of Medicine, Chicago.

The investigators undertook a retrospective analysis that identified men who had undergone radical prostatectomy between 1983 and 2011 and who had a Gleason score of 8-10 in their prostatectomy specimen. A total of 354 patients were found meeting these criteria, and they were stratified into four groups based on their preoperative PSA: <2.5 ng/mL, 2.6-4.0 ng/mL, 4.1-10.0 ng/mL, and >10.0 ng/mL. Clinical cancer stage ranged from cT1-3, and there were no significant differences in the proportion of men with T2/T3 disease among the four groups.

Median duration of follow-up was 77 months, and 7-year outcomes were calculated for each PSA subgroup for biochemical progression-free survival, metastasis-free survival, and cancer-specific survival rates.

Data provide a 'wake-up call'

"These data should provide a wake-up call to physicians who might think there is no need to perform a biopsy in men whose PSA remains low or who might be less concerned about disease aggressiveness in a patient found to have a high-grade tumor but who has a low PSA level," Dr. McGuire said.

Senior author William J. Catalona, MD, told Urology Times that the motivation for the study stemmed from ongoing debate about the need for prostate cancer screening and the relationship defined by the Partin tables between a higher PSA level and an increased likelihood of having an advanced, life-threatening tumor.

"The message from this study is that PSA does not correlate with prognosis across the board, and so I would caution those who argue against routine PSA screening and who believe there is no need to worry about men with a low PSA level that they are sticking their heads in the sand," said Dr. Catalona, professor of urology and director of the clinical prostate cancer program at Northwestern's Robert H. Lurie Comprehensive Cancer Center.

He advocated initiating PSA screening at 40 years of age and performing a biopsy in any man who has a persistently rising PSA on follow-up.

"Management decisions can be guided based on evaluation of the PSA level together with the biopsy findings, but if the Gleason score is high, physicians should be careful not to be misled by a low PSA level," Dr. Catalona said.

The explanation for the paradoxical relationship between PSA level and tumor aggressiveness among men with Gleason 8-10 tumors lies in the knowledge that high-grade tumors that are very poorly differentiated can lose their ability to produce PSA.

This latter phenomenon was demonstrated by the Northwestern researchers using histologic staining to identify PSA-expressing cells that showed abundant staining in normal prostate tissue and Gleason grade 6 tumors, but only minimal staining in prostate cancers with high Gleason grades.