Barcelona, Spain—Results of the new clinical trial RADICALS-RT indicate that using salvage radiotherapy immediately after surgery leads to equivalent outcomes in terms of progression-free survival (PFS) versus adjuvant radiotherapy in men with prostate cancer undergoing radical prostatectomy. These late-breaking results were presented at the ESMO Congress 2019 by lead investigator Chris Parker, MD, FRCR, MRCP, Consultant Clinical Oncologist, Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London, England.
Using the more conservative approach of observation only after surgery, with salvage radiotherapy initiated at the first sign of disease recurrence—as measured by a rise in prostate-specific antigen (PSA) of >0.1 ng/mL or by 3 consecutive rises in PSA level—can avoid the side effects of radiotherapy used as adjuvant treatment in at least 50% of men who will not have biochemical failure, Dr Parker said.
“In RADICALS-RT, adjuvant radiotherapy did not improve biochemical progression-free survival or time to future hormone therapy compared with early salvage radiotherapy. Adjuvant therapy increased urinary and bowel symptoms. These results support early salvage radiotherapy after radical prostatectomy,” said Dr Parker.
“There is a strong case now that observation should be the standard approach after surgery, and radiotherapy should be used only if there is recurrence. Longer follow-up is needed to determine if there is an effect on survival,” Dr Parker said.
“The good news is that in the future, many men will avoid the side effects of radiotherapy, including urinary leakage and narrowing of the urethra, both of which are potential complications after surgery alone, but the risk is increased if radiotherapy is added,” he added.
The prospective phase 3 clinical trial RADICALS-RT enrolled 1396 men after surgery for prostate cancer who had at least 1 risk factor for disease progression—pT3/4 disease, Gleason score 7-10, positive margins, or PSA ≥10 ng/mL—and postoperative PSA ≤0.2 ng/mL. Men were randomized to adjuvant radiotherapy within 4 to 6 months postsurgery or to observation plus salvage radiotherapy to be triggered by 2 consecutive rises in the PSA score.
The primary end point was freedom from distant metastases. The majority of the men had T3 disease and 20% had seminal vesicle involvement. Biochemical progression was defined as PSA rise of >0.1 ng/mL or 3 consecutive rises in PSA level. Nonprotocol hormone therapy was initiated for these thresholds.
Almost all the men randomized to adjuvant radiotherapy received treatment compared with only one-third of those randomized to salvage radiotherapy. Salvage radiotherapy was given relatively early, at a median PSA of 0.2 ng/mL. More than 90% of patients had radiotherapy to the prostate bed alone, and radiotherapy could be given along with hormone therapy.
Dr Parker presented the primary analysis of the trial at the ESMO Congress 2019, focusing on biochemical PFS, freedom from nonprotocol hormone therapy, safety, and patient-reported outcomes.
At a median follow-up of 5 years, adjuvant radiotherapy was initiated within a median of 5 months from surgery compared with a median of 8 years for salvage radiotherapy. Biochemical PFS was 85% for adjuvant radiotherapy and 88% for observation and salvage radiotherapy; freedom from nonprotocol hormone therapy at 5 years was 92% and 94%, respectively.
The investigators analyzed the salvage therapy arm only for freedom from distant metastases: 22 events occurred during follow-up, and 90% of the patients were free from distant metastases.
Although most urinary and bowel adverse reactions were low grade and relatively infrequent, these were more common in the adjuvant therapy arm. According to patient-reported outcomes, no significant difference was seen in urologic and bowel symptoms between the 2 arms.
Importance of Early Salvage Therapy
“Salvage radiotherapy is probably the modality of choice, provided it is early,” said study discussant Gert De Meerleer, MD, PhD, University Hospitals Leuven–Campus Gasthuisberg, Belgium.
“Don’t miseducate yourself or your colleagues. Do not wait until the PSA rises to 0.4 ng/mL, and do not take this into routine clinical practice. You have to refer the patient for radiotherapy early, at 0.2 ng/mL maximum,” he emphasized.