T3 PROSTATE CANCER PATIENTS SHOULD RECEIVE RADIOTHERAPY

June 25, 2009 — There is now additional evidence that supports the use of adjuvant radiation in men with prostate cancer who have undergone radical prostatectomy and have pathologic stage T3 (pT3) disease, according to an editorial published in the June 20 issue of the Journal of Clinical Oncology.

As many as a one third of men undergoing radical prostatectomy are candidates for adjuvant radiation because they have 1 or more of the hallmarks of stage pT3 disease: positive margins, extraprostatic extension, or involvement of the seminal vesicles, say the editorialists, led by Ian Thompson, MD, from the University of Texas Health Science Center in San Antonio.

"A debate has raged for decades over the utility of adjuvant radiotherapy in treating these men," write Dr. Thompson and his coauthors.

The debate has been reopened with the publication of a new study from Germany in the same issue of the journal, which prompted the editorial.

The German study, led by Thomas Wiegel, MD, from University Hospital Ulm, provides further evidence for benefit from radiotherapy. Among 265 men with undetectable prostate-specific antigen (PSA) postsurgery and pT3 disease, the 5-year biochemical progression-free survival was 72% in the group of men randomized to treatment with immediate radiation therapy and 54% in the wait-and-see group.

The new study's findings are similar to 2 other studies that have shown that undergoing radiation therapy within several months of surgery is associated with about a 20% reduction in risk for biochemical progression at 5 years. These 2 studies are the European Organization for Research and Treatment of Cancer (EORTC) 22911 trial (Lancet. 2005;366:572-578) and the Southwest Oncology Group (SWOG) S8794 trial (JAMA. 2006;296:2329-2335).

The new dimension of evidence provided by the German study is that the men in the study all had undetectable PSA after surgery, the authors note.

"In contrast to the other studies, we were able to demonstrate that patients who achieved undetectable PSA after radical prostatectomy do profit from adjuvant radiotherapy," Dr. Wiegel and colleagues write.

Which Patients Most Likely to Benefit?

The German study included a central pathology review in 85% of cases; the EORTC 22911 and SWOG S8794 trials did not. This review indicated which pT3 patients were most likely to benefit from radiotherapy.

"Our findings suggest positive margins, a PSA level more than 10 ng/mL before radical prostatectomy, or extracapsular extension without infiltration of the seminal vesicles to be predictors of an increased effect of radiotherapy," write Dr. Wiegel and colleagues. Positive margins were the strongest predictor of benefit (P = .00018).

EORTC 22911 initially demonstrated a positive treatment effect for all subgroups. However, the researchers have since conducted a reanalysis based on a central pathology review of 50% of the patient specimens, and they now also conclude that positive margins are the strongest predictor of outcome with radiotherapy.

Nonetheless, in the new study, the benefit of adjuvant radiotherapy was seen in all patients, whether they had positive margins or not, Dr. Wiegel and colleagues emphasized.

Wait and See Is Not as Good as Adjuvant Radiation

There is an "emerging standard of care" in the treatment of men who undergo radical prostatectomy and are found to have pT3 disease, write the editorialists. And patients need to know the evidence, they suggest.

The evidence now includes the new German study, which shows that immediate adjuvant radiotherapy with comparatively low doses that are relatively well tolerated reduces the risk for biochemical progression, write the editorialists.

The evidence also includes the SWOG S8794 trial, which was headed by Dr. Thompson, one of the editorialists.

In that study, adjuvant radiotherapy within 18 weeks of surgery significantly reduced the risk for PSA recurrence and metastasis and significantly increased survival, compared with a wait-and-see approach to radiotherapy, as reported by Medscape Oncology earlier this year.

At the time of publishing, one expert, who was acting as an American Urological Association spokesperson, called it a "practice-changing study."

In the editorial, Dr. Thompson and his coauthors are not as forceful, but state their case clearly: "We feel that clinicians cannot tell patients that waiting until a PSA becomes detectable using an ultrasensitive assay is just as good as undergoing adjuvant radiation. Such a statement would be based on faith, not data."

The researchers have disclosed no relevant financial relationships.

J Clin Oncol. 2009;27:2898-2899 and 2924-2930. Abstract, Abstract