The addition of pelvic lymph node treatment and short-term androgen deprivation therapy to prostate bed salvage radiotherapy reduced risk for disease progression among men with prostate cancer, according to findings from a randomized trial presented at the American Society for Radiation Oncology Annual Meeting.
Alan Pollack, MD, chair of the department of radiation oncology at the University of Miami Sylvester Comprehensive Cancer Center, and colleagues investigated three treatment regimens among 1,792 patients enrolled in the SPPORT trial between 2008 and 2015.
Patients were randomly assigned prostate bed salvage radiotherapy alone, radiotherapy plus short-term ADT, or radiotherapy plus short-term ADT and pelvic lymph node treatment.
“Biochemical failure after [prostate bed salvage radiotherapy] is typically 30% to 40% at about 5 years,” Pollack said in a press conference. He noted that when the study was designed in 2005, there was little data on neoadjuvant concurrent ADT and pelvic lymph node treatment. “Since that time, it has been shown that there is benefit of ADT. In terms of pelvic lymph node radiation therapy, there really has never been a conclusive trial showing a benefit. That’s what prompted us to include this in the SPPORT trial.”
The primary endpoint was freedom from progression (FFP), which included PSA nadir+2, clinical failure or all-cause mortality.
“The hypothesis in this three-arm trial was that we would see an incremental benefit in FFP by addition of short-term ADT, and a further incremental benefit by treating the pelvic lymph node in addition to short-term ADT,” Pollack said. “This is the first trial to document that effect in a salvage setting.”
Pollack presented findings for 1,736 eligible patients (median age, 64 years; range, 39-84) with a median follow-up duration of 5.4 years.
Results showed that prostate bed salvage radiotherapy alone yielded an FFP rate of 71.1%, compared with 82.7% for the second group, which received radiotherapy and short-term ADT, and 89.1% for the third group, which received radiotherapy, ADT and pelvic lymph node treatment. Compared with the first group, the third group had the higher FFP rate (HR = 0.44; 95% CI, 0.32-0.59). The difference in FFP between groups two and three was 6.4% (HR = 0.71; 95% CI, 0.51-0.98).
“This was exactly what we predicted at outset of this study,” Pollack said of the FFP rate for the radiotherapy-alone group. “You can see that even comparing arm three to arm two, there was a statistically significantly difference in this analysis.”
Among eligible participants followed for up to 8 years, distant metastases were reported among 45 men in the first group, 38 men in the second group, and 25 men in the third group.
In an analysis where second salvage censoring was not included, the hazard ratio for distant metastases was 0.52 (95% CI, 0.32-0.85) for group three vs. group one and 0.64 (95% CI, 0.39-1.06) for group three vs. group two.
“Remember, this is an early release of the data, so it is surprising to see even a trend in distant metastases at this point,” Pollack said. “There were only 108 patients with distant metastases.”
Clinicians used intensity-modulated radiation therapy in 87% of cases. Grade 3 or higher renal or genitourinary events occurred in 4.3% of men in group one, 4.9% of men in group two and 6% of men in group three. For grade 3 or higher gastrointestinal events, the rates were 0.7% for the first group, 0.4% for the second and 1.1% for the third.
“In terms of toxicity, there were some differences with the addition of pelvic lymph node treatment,” Pollack said.
Pollack concluded that this is currently the strongest level one evidence supporting the use of pelvic lymph node treatment in this population.
“The number needed to treat to prevent one progression at 5 years is six, which is a very low number,” he said. “It is beginning to translate into a difference in distant metastases. One of the key questions is, should we look at a cut point of patients who don’t need pelvic lymph node radiation? It may be too early to tell.” — by Rob Volansky
Pollack A, et al. Abstract LBA-5. Presented at: American Society for Radiation Oncology Annual Meeting; Oct. 21-24, 2018; San Antonio.
Disclosures: Pollack reports research grants from Varian and Varian Medical Systems.