Radiation therapy with curative intention in men with de novo metastatic prostate carcinoma: shoot ‘em all!
Abstract
BACKGROUND: About 5% of prostate cancer cases are metastatic at diagnoses. Radiotherapy of both primary tumor and secondary lesions can be, in addition to systemic treatments, a radical alternative for selected patients.
MATERIALS AND METHODS: Patients with de novo prostate carcinoma with bone or lymph node metastases were retrospectively reviewed. All patients received moderate hypofractionated IMRT/VMAT up to 63 Gy in 21 daily fractions of 3 Gy to prostate and metastases with neoadjuvant and concurrent androgen deprivation therapy (ADT). According to known advances some patients also received abiraterone, enzalutamide, or docetaxel.
RESULTS: Between 2015–2020, we attended 26 prostate cancer patients (median age 69.5 years, range 52–84) with simultaneous oligometastases [mean 2.1 metastases, median 1.5 metastases (range 1–6)]. Eighteen patients (69%) presented lymph node metastases, 4 (15.5%) bone metastases and 4 (15.5%) both lymph node and bone metastases. With a median follow-up of 15.5 months (range 3–65 months), 16 patients (62%) are alive and tumor free while 10 (38%) are alive with tumor. Four patients (17%) developed tumor progression, out of irradiated area in all cases, with a median time to progression of 43.5 months (range 27–56 months). Actuarial progression-free survival (PFS) rates at 12 and 24 months were 94.1% and 84.7%, respectively. No grade > 2 acute or late complications were recorded.
CONCLUSIONS: Simultaneous directed radical hypofractionated radiation therapy for prostate and metastases is feasible, well tolerated and achieves an acceptable PFS rate. However, further studies with longer follow-up are necessary to definitively address these observations.
Keywords: prostate cancerde novo oligometasteshypofractionated radiotherapymetastases-directed therapy
References
- Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394–424.
- Buzzoni C, Auvinen A, Roobol MJ, et al. Metastatic Prostate Cancer Incidence and Prostate-specific Antigen Testing: New Insights from the European Randomized Study of Screening for Prostate Cancer. Eur Urol. 2015; 68(5): 885–890.
- Francini E, Gray KP, Xie W, et al. Time of metastatic disease presentation and volume of disease are prognostic for metastatic hormone sensitive prostate cancer (mHSPC). Prostate. 2018; 78(12): 889–895.
- Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995; 13(1): 8–10.
- Lecouvet F, Oprea-Lager D, Liu Y, et al. Use of modern imaging methods to facilitate trials of metastasis-directed therapy for oligometastatic disease in prostate cancer: a consensus recommendation from the EORTC Imaging Group. Lancet Oncol. 2018; 19(10): e534–e545.
- Finianos A, Gupta K, Clark B, et al. Characterization of Differences Between Prostate Cancer Patients Presenting With De Novo Versus Primary Progressive Metastatic Disease. Clin Genitourin Cancer. 2017 [Epub ahead of print].
- Futterer JJ, Surcel C, van den Bergh R, et al. EAU-YAU Prostate Cancer Working Party. Imaging modalities in synchronous oligometastatic prostate cancer. World J Urol. 2019; 37(12): 2573–2583.
- Perez-Lopez R, Tunariu N, Padhani AR, et al. Imaging Diagnosis and Follow-up of Advanced Prostate Cancer: Clinical Perspectives and State of the Art. Radiology. 2019; 292(2): 273–286.
- Gandaglia G, Karakiewicz PI, Briganti A, et al. Impact of the Site of Metastases on Survival in Patients with Metastatic Prostate Cancer. Eur Urol. 2015; 68(2): 325–334.
- Halabi S, Kelly WK, Ma H, et al. Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men With Castration-Resistant Prostate Cancer. J Clin Oncol. 2016; 34(14): 1652–1659.
- Boevé LMS, Hulshof MC, Vis AN, et al. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. Eur Urol. 2019; 75(3): 410–418.
- Parker CC, James ND, Brawley CD, et al. Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018; 392(10162): 2353–2366.
- James ND, Spears MR, Clarke NW, et al. STAMPEDE Investigators. Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial. JAMA Oncol. 2016; 2(3): 348–357.
- Kim MY, Oskarsson T, Acharyya S, et al. Tumor self-seeding by circulating cancer cells. Cell. 2009; 139(7): 1315–1326.
- Demaria S, Ng B, Devitt ML, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 2004; 58(3): 862–870.
- Kyriakopoulos C, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. Journal of Clinical Oncology. 2018; 36(11): 1080–1087.
- Burdett S, Boevé LM, Ingleby FC, et al. STOPCAP M1 Radiotherapy Collaborators. Prostate Radiotherapy for Metastatic Hormone-sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta-analysis. Eur Urol. 2019; 76(1): 115–124.
- Zaorsky NG, Palmer JD, Hurwitz MD, et al. What is the ideal radiotherapy dose to treat prostate cancer? A meta-analysis of biologically equivalent dose escalation. Radiother Oncol. 2015; 115(3): 295–300.
- Ost P, Reynders D, Decaestecker K, et al. Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. J Clin Oncol. 2018; 36(5): 446–453.
- Ost P, Reynders D, Decaestecker K, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): Five-year results of a randomized phase II trial. J Clin Oncol. 2020; 38(6_suppl): 10–10.
- Phillips R, Shi WY, Deek M, et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020; 6(5): 650–659.
- De Bruycker A, Spiessens A, Dirix P, et al. PEACE V — Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): a study protocol for a randomized controlled phase II trial. BMC Cancer. 2020; 20(1): 406.
- Cho Y, Chang JS, Rha KHo, et al. Does Radiotherapy for the Primary Tumor Benefit Prostate Cancer Patients with Distant Metastasis at Initial Diagnosis? PLoS One. 2016; 11(1): e0147191.
- Tsumura H, Ishiyama H, Tabata KI, et al. Long-term outcomes of combining prostate brachytherapy and metastasis-directed radiotherapy in newly diagnosed oligometastatic prostate cancer: A retrospective cohort study. Prostate. 2019; 79(5): 506–514.
- Reverberi C, Massaro M, Osti MF, et al. Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer. Sci Rep. 2020; 10(1): 17471.
- Imber BS, Varghese M, Goldman DA, et al. Clinical Outcomes of Combined Prostate- and Metastasis-Directed Radiation Therapy for the Treatment of De Novo Oligometastatic Prostate Cancer. Adv Radiat Oncol. 2020; 5(6): 1213–1224.
- Deantoni CL, Fodor A, Cozzarini C, et al. Prostate cancer with low burden skeletal disease at diagnosis: outcome of concomitant radiotherapy on primary tumor and metastases. Br J Radiol. 2020; 93(1108): 20190353.