October 21, 2023
Radiotherapy After Radical Prostatectomy Offers No Benefit
By Catlin Nalley
Adjuvant radiotherapy following radical prostatectomy demonstrated no meaningful benefit for patients with prostate cancer, according to final results from the Phase III RADICALS-RT study (NCT00541047) presented during the European Society for Medical Oncology (ESMO) Congress 2023, held October 20-24 in Madrid, Spain (Abstract 1764O).
The data, which also showed that adjuvant radiotherapy increases the risk of urinary and bowel morbidity, support previously reported findings (Lancet 2020;396:1413-21) and confirm that observation with early salvage radiotherapy in cases of biochemical failure should be the standard approach following surgery, according to presenter and study author Noel Clarke, MBBS, FRCS, ChM, a consultant urologist at Salford Royal Hospital & The Christie, Manchester, UK.
Study Details
A number of studies have explored the timing of radiotherapy after radical prostatectomy, noted Clarke, and RADICALS-RT—which aimed to shed light on the optimal timing of radiotherapy for prostate cancer patients following surgery—is the largest.
This Phase III clinical trial examined the efficacy and safety of adjuvant radiotherapy in comparison to an observation policy coupled with salvage radiotherapy for early PSA failure. It included patients who were 4-22 weeks post-radical prostatectomy with a postoperative PSA of ≤0.2 ng/mL and at least one of the following risk factors: pT3/4, Gleason score 7-10, positive margins, or preoperative PSA ≥10 ng/mL.
Eligible participants were randomized 1:1 to receive adjuvant radiotherapy or observation plus salvage radiotherapy at biochemical relapse—defined as two consecutive rises with a PSA ≥0.1 ng/mL or three consecutive rises. Stratification factors included Gleason score, margin status, planned radiotherapy volume (prostate bed only, prostate bed plus pelvis), radiotherapy schedule (52.5Gy/20f, 66Gy/33f), and centre.
“The primary outcome measure was freedom from distant metastases with >1,200 patients needed for 80 percent power to detect an improvement from 90 percent to 95 percent at 10 years with adjuvant radiotherapy,” according to Clarke and colleagues. “Secondary outcome measures include overall survival, safety, and patient-reported outcome measures (1, 5, 10 years). Standard survival analysis methods were used.”
From October 2007 to December 2016, researchers recruited and randomized 1,396 patients across the UK (82%), Denmark (13%), Canada (4%), and Ireland (1%) with a median age of 65 years. Of these patients, 697 received adjuvant radiotherapy and 699 underwent observation plus salvage radiotherapy for PSA failure.
With 80 events (32 adjuvant radiotherapy, 48 salvage radiotherapy), Clarke reported similar rates of 10-year freedom from distant metastases between the two arms. Specifically, 93 percent in patients who received adjuvant radiotherapy compared with 90 percent among those in the observation plus salvage therapy cohort. The researchers also observed similar overall survival rates of 88 percent and 87 percent, respectively.
When looking at patient-reported outcomes in the long term, Clarke noted that urinary and fecal incontinence rates at 1 year were significantly worse among the adjuvant radiotherapy group when compared with the observation cohort. Approximately 60 percent of patients in the observation plus salvage radiotherapy group had not yet needed to undergo radiotherapy.
The study authors found that secondary outcome measures—including biochemical progression-free survival and time to further hormone therapy—were similar in both patient groups, according to Clarke.
“In conclusion, the long-term biochemical progression-free survival and time to further hormone therapy was similar for the adjuvant and early salvage groups,” Clarke summarized. “Early salvage radiotherapy is as effective as adjuvant radiotherapy regarding the long-term failure for metastatic disease and overall survival. However, the adjuvant radiotherapy group had a higher long-term urinary and bowel morbidity.
“A large proportion of men randomized to early salvage radiotherapy didn't need radiotherapy in the long term and they weren't in any way disadvantaged when they failed,” he concluded. “RADICALS supports the use of early salvage radiotherapy for PSA failure after radical prostatectomy rather than early adjuvant intervention.”
Invited discussant and session co-chair Shahneen Sandhu, MBBS, Associate Professor and Consultant Medical Oncologist at Peter MacCallum Cancer Centre, Victoria, Australia, highlighted the implications of these long-term findings.
“Overall, there is no benefit from adjuvant radiation compared to early salvage radiation,” she emphasized during the ESMO presentation. “Early salvage radiation spares the vast majority of patients from having radiation [and] the morbidity from early salvage radiation is low.”
Catlin Nalley is a contributing writer.