ASCO 2018: Prostate Radiotherapy in Newly-Diagnosed Metastatic Hormone-Sensitive Prostate Cancer

Chicago, IL (UroToday.com) The role of radiation therapy (RT) for the treatment men with localized prostate cancer is complex but well established. However, the role of radiation for men with metastatic hormone sensitive prostate cancer is much more ambiguous. In mouse models, it has been suggested that RT to the primary tumor may reduce angiogenesis in metastatic sites, suggesting a helpful abscopal effect1. During the 2017 Advanced Prostate Cancer Consensus Conference, 52% of the members recommended against treating the primary tumor in addition to systemic therapy in men with metastatic castration naïve prostate cancer2. For patients with metastatic castration resistant prostate cancer, 60% voted for the addition of local treatment. 

Two separate retrospective analyses, both published in 2016, have been performed to examine this exact question. In the first study, 6,382 men with metastatic prostate cancer were identified from the NCDB, of which 538 (8.4%) received prostate RT. At a median follow up of 5.1 years, the addition of prostate RT to ADT was associated with improved overall survival (HR 0.624; 95% CI, 0.551 to 0.706; P<.001) on univariate as well as multivariate analysis after adjusting for age, year, race, comorbidity score, PSA level, Gleason score, T stage, N stage, chemotherapy administration, treating facility, and insurance status3. Patients receiving prostate RT had superior median survival (55 vs 37 months) as well as greater 5 year overall survival (49% vs 33%). In the second study, the exact same database (NCDB) was used. 15,501 patients were identified as having metastatic prostate cancer and 9.5% received localized therapy4. In this study, localized therapy could include radical prostatectomy as well as radiation therapy. They too found that localized therapy improved three year overall mortality (69% vs 54%; p < 0.001).

In this single center study, 304 patients with newly diagnosed metastatic prostate cancer were referred for therapy. 105 patients received prostate RT. On univariate analysis, receipt of prostate RT was associated with an improved overall survival (HR 0.62, 95% CI 0.46-0.84, p = 0.002). The hazard ratio is remarkably identical to the retrospective study performed by Rusthoven et al in 2016. Five-year overall survival was 41.8% in patients receiving RT and 27.6% in those who did not receive RT (14.2% increase in 5-year overall survival). This too is similar to the finding in the earlier study showing a 16% overall improvement in 5 year survival overall survival. After controlling for age at diagnosis, year of diagnosis, presenting PSA, T stage, N stage, and M1 subdivision, receipt of RT remained associated with improved overall survival (HR 0.64, 95% CI 0.43-0.96, p = 0.033). The authors note that that their analysis could not account for performance status, volume of metastatic disease, comorbidities, receipt of systemic therapies, and other potential confounders.

However, as was noted by Dr. Timur Mitin during the poster discussion session, if you compare the overall survival of the patients who survived over 1 year, there did not appear to be any difference in overall survival, suggesting that perhaps there is selection bias in who had been referred for therapy. The HORRAD trial presented at AUA 2018 also suggested that there was no overall survival benefit associated with receipt of EBRT to the prostate for patients with primary bone metastatic prostate cancer5.

In conclusion, at this time, there is no definitive survival benefit from the addition of local therapies in M1 prostate cancer. It does appear that local therapy may have the ability to delay ADT initiation with fairly low toxicity, and could be considered early on in M1 disease to control symptoms related to the primary disease. 

Presented by: Timur Mitin, MD PhD
Abstract By: Scott Carlyle Morgan, MD. Division of Radiation Oncology, University of Ottawa

Written By: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University @TheRealJasonZhu at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA

References:

1. Hartford AC, Gohongi T, Fukumura D, Jain RK. Irradiation of a Primary Tumor, Unlike Surgical Removal, Enhances Angiogenesis Suppression at a Distal Site: Potential Role of Host-Tumor Interaction. Cancer Research 2000;60:2128-31.

2. Gillessen S, Attard G, Beer TM, et al. Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017. European Urology 2018;73:178-211.

3. Rusthoven CG, Jones BL, Flaig TW, et al. Improved Survival With Prostate Radiation in Addition to Androgen Deprivation Therapy for Men With Newly Diagnosed Metastatic Prostate Cancer. Journal of Clinical Oncology 2016;34:2835-42.

4. Löppenberg B, Dalela D, Karabon P, et al. The Impact of Local Treatment on Overall Survival in Patients with Metastatic Prostate Cancer on Diagnosis: A National Cancer Data Base Analysis. European Urology 2017;72:14-9.

5. Boevé L, Hulshof M, Vis A, et al. PD10-10 A Prospective, Randomized Controlled Trial Evaluating Overall Survival In Patients With Primary Bone Metastatic Prostate Cancer (Mpca) Receiving Either Androgen Deprivation Therapy (Adt) Or Adt Combined With Concurrent Radiation Therapy To The Prostate, Final Data From The Horrad Trial. The Journal of Urology 2018;199:e231-e2.A Prospective, Randomized Controlled Trial Evaluating Overall Survival In Patients With Primary Bone Metastatic Prostate Cancer (Mpca) Receiving Either Androgen Deprivation Therapy (Adt) Or Adt Combined With Concurrent Radiation Therapy To The Prostate, Final Data From The Horrad Trial. The Journal of Urology 2018;199:e231-e2.







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