New research presented at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting indicates that targeting both the primary tumor and metastatic lesions with radiation therapy, known as total consolidative therapy (TCT), significantly improves 5-year survival rates in patients with oligometastatic hormone-sensitive prostate cancer (omHSPC). The findings from the single-center PROLONG study challenge current clinical guideline recommendations that suggest radiation therapy should only target the primary tumor in these patients.
The PROLONG trial, led by Xin Qi, MD, MS, of Peking University First Hospital, assessed the safety and survival outcomes of patients with omHSPC based on radiation therapy targets. The ambispective cohort analysis included 395 patients treated between October 2011 and January 2022. Participants had pathologically confirmed prostate cancer with imaging showing ≤10 distant metastases. The cohort comprised mostly oligo-metastatic (53.7%), oligo-progressive (26.6%), oligo-recurrent (14.7%), and oligo-persistent (1.8%) cases.
Patients received daily image-guided rotational intensity modulated radiotherapy (IGRT-VMA) either targeting both the primary tumor and all metastatic lesions (TCT) or just the primary tumor. Overall survival and progression-free survival (PFS) were calculated using the Kaplan-Meier method, log rank test, and Cox regression models. The median primary tumor biologically effective dose (BED3) was 135.3Gy, and the team irradiated 718 total metastases with a median BED3 of 121.3Gy. The median follow-up time was 60 months.
The results showed that 115 patients had died by the time of data publication. Overall survival rates were 93.2% at 3 years and 79.5% at 5 years, with a median overall survival of 102 months. Notably, Gleason score and prostate-specific antigen (PSA) levels at diagnosis were identified as independent prognostic factors for overall survival. Only 4.6% of treated patients experienced an acute genitourinary or gastrointestinal toxicity grade ≥2.
Outcomes by Metastatic State
In the de-novo oligo metastasis subgroup, median overall survival and PFS rates were not reached among patients receiving TCT. Patients with higher PSA or T1/2 scores at baseline were more likely to report improved PFS. Among the oligo-recurrence group, the median overall survival rate was not reached, and the median PFS was 37 months. For the oligo-progressive group, median overall survival was 85 months (95% CI, 65 – 105), and median PFS was 11 months (95% CI, 8.5 – 13.5). In the oligo-persistence group, median overall survival and PFS were not reached.
Implications and Conclusions
Qi and colleagues concluded that the 5-year results of the PROLONG study demonstrated excellent tolerability of TCT in patients with omHSPC and promising long-term efficacy based on survival rates.
According to the research team, "Radiation therapy for the primary tumor and all metastatic lesions has better survival than clinical studies of prostate radiotherapy alone, especially for patients with HSPC, shorter interval between diagnosis and radiation therapy, and lower metastatic burden/volume."
