Most men who undergo radical prostatectomy can skip adjuvant radiotherapy and can be followed with observation alone. They can undergo early salvage radiotherapy if the disease shows sign of progressing, say experts reporting results from three similar clinical trials.
This approach would allow most men to avoid radiotherapy and its side effects altogether, the investigators emphasize.
The studies were published online September 28 in The Lancet and The Lancet Oncology.
“There is a strong case now that observation should be the standard approach after surgery and [that] radiotherapy should only be used if the cancer comes back,” commented Chris Parker, MD, the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London, United Kingdom.
“Results suggest that radiotherapy is equally effective whether it is given to all men shortly after surgery or given later to those men with recurrent disease,” he said in a statement.
Parker was lead investigator on the largest of the studies, the phase 3 RADICALS-RT trial, published in The Lancet. Preliminary results were reported at a meeting last year. Similar results from two other trials were published in The Lancet Oncology. A preplanned meta-analysis of the three trials was published in The Lancet.
Despite a number of limitations to each of the studies, they represent “an important step forward” and support the use of early salvage radiotherapy for many patients following radical prostatectomy, write experts in an accompanying comment. The editorialists are Derya Tilki, MD, University Hospital Hamburg-Eppendorf, Hamburg, Germany, and Anthony D’Amico, MD, Brigham and Women’s Hospital and the Dana Farber Cancer Institute, Boston, Massachusetts.
However, the editorialists question whether the results apply to all men who have undergone a radical prostatectomy.
One possible exception are men at high risk for progression, such as patients with a Gleason score of 8 to 10 or whose tumor is of grade pT3b or higher. Such patients made up fewer than 20% of participants in the three clinical trials. For high-risk patients, the editorialists think it would be “prudent” to consider adjuvant radiotherapy rather than early salvage therapy.
Results From RADICALS-RT
The RADICALS-RT trial involved 1396 patients who were followed for a median of 4.9 years. Participants had to have at least one risk factor for biochemical progression. These factors included disease of pathologic T-stage 3 or 4, a Gleason score of 7 to 10, positive margins, or a preoperative prostate-specific antigen (PSA) level ≥10 ng/mL.
Half of the men were randomly assigned to receive adjuvant radiotherapy (delivered within 6 months of study enrollment for 90% of patients). One quarter of this group also received either neoadjuvant or adjuvant hormone therapy, the investigators note.
The other half were followed with observation and received salvage radiotherapy group only if they showed biochemical progression within 8 years following randomization.
There was no evidence of a difference in biochemical progression-free survival (bPFS) between the adjuvant and salvage groups, Parker and colleagues report. At 5 years, bPFS rates were 85% for men in the adjuvant radiotherapy group and 88%