The Road to Radiotherapy

The SWOG 8794 trial was conducted between 1988 and 1997 in the United States and randomly assigned 425 men with non-organ confined cancer or positive surgical margins to either immediate adjuvant radiotherapy after RP or a wait-and-see protocol.2 It found that adjuvant radiotherapy after RP provided a benefit in terms of PSA levels and local control and significantly reduced the risk of metastasis and increased survival.

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A similarly designed study was conducted in Germany more recently.  It began in 1996 and the findings were similar to the study by Bolla and colleagues, but with a much shorter follow-up time.3   In this trial, 192 men were randomly assigned after RP to a wait-and-see policy and 193 were assigned to immediate postoperative radiotherapy.  It showed that adjuvant radiotherapy significantly reduced the risk of biochemical recurrence for patients with pT3 prostate cancer and undetectable PSA levels following RP.  The biochemical PFS rate after 5 years of follow-up was 72% in the adjuvant radiotherapy arm compared to 54% in the wait-and-see arm.

“While the most recent EORTC update does not show an overall survival advantage, it shows some real benefit,” said Jason A. Efstathiou, MD, DPhil, an Assistant Professor in the Department of Radiation Oncology at Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, who wrote the invited associated comment to the EORTC update in the Lancet. 4 “All three randomized trials have a consistent message.  They all show a significant benefit in terms of avoiding biochemical recurrence, local failure, and the potential subsequent need for salvage therapy such as hormonal therapy.”

Dr. Efstathiou noted that studies to date have not yet fully addressed the optimal timing to deliver postoperative radiotherapy to men who undergo RP.  However, trials are now underway comparing immediate adjuvant radiotherapy versus early salvage therapy at the time of PSA failure.  Dr. Efstathiou said when considering initiating adjuvant radiation, it is important that patients are not treated too early after RP, and maximum recovery of urinary control should be established as much as possible before initiating postoperative radiotherapy.  He added that novel imaging modalities are now being assessed as tools to help guide clinicians when it comes to the use of radiotherapy following RP.

“Most trials initiate adjuvant radiation about 4 months after surgery.  I personally like to wait 4 to 6 months to let the patient recover and achieve maximum urinary control.  One can stunt this recovery, if you treat them too soon,” said Dr. Efstathiou in an interview with Chemotherapy  “MRI- and PET-based imaging are being explored to see whether or not they can determine which patients can benefit from adjuvant therapy.  These imaging modalities may be able to identify early recurrent disease and its location and therefore better guide the use of post operation radiation.”