Michel Bolla, MD
Patients with localized prostate cancer at intermediate or high risk for progression experience better outcomes when 6 months of androgen deprivation therapy (ADT) is added to standard radiotherapy, according to a presentation at the 2014 European Society for Radiotherapy and Oncology (ESTRO) annual conference.
After a median of 5 years, 82.5% of patients treated with radiotherapy combined with ADT were biochemically progression-free compared with 69.3% of patients treated with radiotherapy alone. Additionally, 88.7% of patients in the combination treatment arm were clinically progression-free compared with 80.8% of patients in the radiotherapy-alone arm. In a median 7.2-month follow-up, 70.7% compared with 50.6% of patients were biochemically progression-free, for the combination and single-agent, respectively.
“These results show that, in men with localized prostate cancer that is at risk of recurring and spreading, the addition of six months of hormonal treatment to radiotherapy improves the time these men survive without their disease progressing,” lead investigator Michel Bolla, MD, professor of radiation oncology at Grenoble University Hospital, France, said in a release. “It is important to ensure that the radiation treatment is of the best quality; further clinical research is required to optimize radiation techniques and to find new hormonal treatments.”
The trial consisted of 819 patients at intermediate or high risk by D'Amico classification whose median age was 70 years. Patients were staged cT1b-c with PSA ≥ 10ng/mL, Gleason score ≥7, or cT2a (UICC TNM 1997) with no spread to regional lymph nodes or distant metastases with PSA≤ 50 ng/mL. Biochemical progression was defined as an increase in PSA of more than 2 ng/mL.
Patients were randomized 1:1 to received radiotherapy alone (n = 409) or radiotherapy plus two subcutaneous injections of an LHRH analogue (n = 410). Six patients refused treatment and 3 patients in the combination arm received radiation therapy alone. To prevent flare, patients in the combination group also received 1 month of 50-mg bicalutamide daily starting 15 days before the first injection. Physicians were able to choose between radiation doses of 70, 74, or 78 Gy.
Following a median 7.2-year follow-up, 118 patients in the combination treatment arm experienced biochemical progression compared with 201 patients in the radiotherapy arm, representing a 47% reduction in risk of biochemical progression with the combination (HR = 0.53; CI, 0.42-0.67, P
< .001). By clinical parameters, the combination reduced the risk of progression by 37% compared with radiotherapy-alone (HR=0.63; CI, 0.48-0.84; P
Late genitourinary toxicity was experienced by 5.9% of patients in the radiotherapy and ADT treatment arm versus 3.6% of patients in the radiotherapy-alone arm. Severe issues with sexual function were also observed in a greater proportion of those treated with the combination versus radiotherapy alone (27% and 19.4%, respectively). At the time of the study’s presentation at ESTRO, 152 patients had died, 25 of which were from prostate cancer.
“This combined treatment approach should be one of the options proposed for men with localized prostate cancer that has an intermediate or high risk of growing and spreading,” Bolla said. “Although we need longer follow-up to assess the impact on these men’s overall survival, these findings need to be taken into account in daily clinical practice.”
Vincenzo Valentini, MD, the president of ESTRO and a radiation oncologist at the Policlinico Universitario A. Gemelli in Rome, Italy, said in a release that these findings are practice changing.
“It is clear that an additional 6 months of hormonal treatment in addition to radiotherapy improves the outcome for men with localized prostate cancer,” Valentini said. “This option should now be considered for all these men with prostate cancer that is at risk of growing and spreading.”