A Publication of the James Buchanan Brady Urological Institute Johns Hopkins Medical Institutions

When PSA Goes Up After Surgery
Is it Local Recurrence? Distant Metastasis? Would Radiation Help?

The return of PSA to the bloodstream after radical prostatectomy is a terrifying prospect for men who have already undergone so much: Stressful diagnosis of prostate cancer, difficult surgery to treat it, and then the big waiting game -- living, as one patient comments, "from one PSA test to the next," hoping the coast will finally be declared clear.

Perhaps worst of all is the uncertainty created by PSA's reappearance: If the cancer is indeed back, is it still localized to the prostate, or has it spread elsewhere? Could radiation therapy eradicate the disease -- or would it just cause new complications by needlessly treating an area already free of cancer?

Two studies by Hopkins researchers have shed much light on these troubling questions. The first, led by urologist Alan W. Partin, M.D., Ph.D., studied rising PSA levels in 51 men after radical prostatectomy. In 30 percent of these men, cancer returned locally, in 70 percent, the cancer showed up in distant metastases. Based on this study, the scientists found they can estimate which course the cancer will take using the combination of Gleason score, pathologic stage (the definitive extent of a man's cancer, determined after surgery, when a pathologist looks at the actual prostate specimen and dissected lymph nodes, if any), and timing -- when the PSA starts to rise, and by how much.

Men most prone to distant metastases, they found, will have one or more of these conditions: Gleason scores of 8 or higher, cancer found in their seminal vesicles and lymph nodes during surgery, or a rise in PSA within a year after their surgery. On the other hand, men with Gleason scores of 7 of lower, low pathologic stage and/or increases in PSA several years after surgery most likely will have only a local recurrence of cancer -- which means their cancer may still be cured with external-beam radiation treatment to the prostate bed, the area where the prostate used to be, where some residual cancer cells may yet be hiding.

Men most likely to benefit from radiation after prostatectomy
  • Gleason score of 7 or lower and
  • Negative seminal vesicles and lymph nodes and
  • Recurrence of PSA more than a year after surgery

Men most likely not to benefit

  • Gleason score of 8 or higher or
  • Positive seminal vesicles or lymph nodes or
  • PSA recurrence within a year after surgery

The next study confirmed these findings, and took them one step further: It actually followed the men through radiation therapy: "We found that no man with a Gleason score of greater than 7, positive lymph nodes, or positive seminal vesicles responded favorably to radiation therapy," says urology resident Jeffery Cadeddu, M.D., who presented the results of the second study at the 1997 annual meeting of the American Urological Association. "So in those patients, we do not recommend radiation therapy."

But, even if it couldn't reach a distant metastases -- a chunk of cancer that has broken off from the main tumor and established itself elsewhere -- couldn't radiation do some more good to the prostate bed? Could it buy any time at all? For a man with metastatic disease, irradiating the pelvis -- ironically, an area where the cancer probably is not -- "does not change survival," Cadeddu says. In addition, radiation therapy to the pelvis in a man, who has undergone a radical prostatectomy may cause incontinence and diminish sexual function.

Conversely, for men with a Gleason score of 7 or less, and negative seminal vesicles and lymph nodes, the longer the period before PSA starts to rise, the better the odds that radiation therapy will be worthwhile.

This study also had an unexpected finding: If radiation therapy in men with elevated PSA levels was delayed until the local recurrence was palpable (if it was big enough for a doctor to feel), these men appeared to do just as well as those who received radiation earlier. If this finding is confirmed in other studies, it might simplify at least one immediate treatment decision in men with elevated PSA levels: The best course may be simply for doctors to follow these men closely; and then, if they develop local recurrence of cancer, to treat them with radiation therapy, or to begin hormone therapy if distant metastases are found.

Further Reading

"Evaluation of Serum Prostate-Specific Antigen Velocity After Radical Prostatectomy to Distinguish Local Recurrence From Distant Metastases." Urology, May 1994, Vol. 43, No. 5, pp. 649-659. Alan W. Partin, Jay D. Pearson, Patricia K. Landis, H. Ballentine Carter, Charles R. Pound, J. Quentin Clemens, Jonathan I. Epstein, Patrick C. Walsh. 

"Long-Term Results of Radiation Therapy for Isolated PSA Elevations Following Radical Prostatectomy," presented at the 1997 annual meeting of the American Urological Association. Patrick C. Walsh, Jeffery A. Cadeddu, Alan W. Partin, Theodore L. DeWeese.


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