SURVIVAL EFFECT OF PALLIATIVE RADIOTHERAPY IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER DEVELOPING OLIGO-PROGRESSION UNDER ANTIANDROGEN TREATMENT

Yıl 2023, Cilt: 86 Sayı: 2, 117 - 122, 30.03.2023

Sabin Goktas Aydın Yasin Kutlu Harun Muğlu Ozgur Acikgoz Ahmet Aydin Ahmet Bilici Ömer Ölmez Dilek Ünal Ebru Karci Özcan Yıldız

https://doi.org/10.26650/IUITFD.1211556

Öz

Objective: Androgen pathway inhibitors have a significant impact on the treatment of prostate cancer. The treatment approach is controversial in patients who develop oligo-progression under anti-androgen therapy. This study aimed to investigate the effects of metastasis-directed stereotactic body radiotherapy (SBRT) on survival in the first-line setting of patients with metastatic castration-resistant prostate cancer who continued the antiandrogen therapy after oligo-progression. Materials and Methods: Fifty-seven metastatic castration-resistant (serum testosterone <50 ng/dl) prostate cancer patients treated with abiraterone or enzalutamide in the first-line setting were analysed retrospectively. Thirty-nine of the patients with the oligo-progressive disease, which was defined as ≤3 lesions on imaging, received SBRT by continuing the same antiandrogen therapy. Results: The median age was 70 (range 40-85). In the castration- sensitive setting, 27 (47.4%) patients received docetaxel. The oligo-progressive metastatic sites were as follows: bone in 21 (52.3%), lymph node in 6 (15.3%) and visceral metastasis in 12 (30.9%) patients. Abiraterone and enzalutamide were preferred in 47.4% and 52.6% of patients, respectively. The 12-month progression- free survival (PFS) was 79.0% and 88.9% in patients who received or did not receive SBRT (p<0.001). SBRT-related grade 1-2 toxicity was observed in 35 (61.4%) patients. SBRT was also an independent risk factor for PFS (p=0.007, HR:15.7; 95% CI 2.05-118.7). The presence of visceral metastases, isolated bone metastases, the choice of anti-androgen therapy, and Eastern Cooperative Oncology Group Scale Performance Status (ECOG PS) were not significantly associated with PFS. SBRT had no impact on overall survival. Conclusion: Patients treated with metastasis-directed SBRT without changing treatment in the oligo-progression setting had worse survival outcomes. Thus, metastasis-directed SBRT with continuation of the same antiandrogen therapy should be prioritised only in selected cases.

Anahtar Kelimeler

Stereotactic body radiotherapy, abiraterone, enzalutamide, castration-resistant prostate cancer

ANTİANDROJEN TEDAVİSİ ALTINDA OLİGO-PROGRESYON GELİŞEN METASTATİK KASTRASYONA DİRENÇLİ PROSTAT KANSERLİ HASTALARDA METASTAZA YÖNELİK VÜCUT RADYOTERAPİSİNİN SAĞKALIM ETKİSİ

Öz

Amaç: Androjen yolağı inhibitörleri prostat kanserinin tedavisinde önemli etkiye sahiptir. Anti-androjen tedavisi altında oligo- progresyon gelişen hastalarda tedavi yaklaşımı tartışmalıdır. Bu çalışma, metastaza yönelik stereotaktik vücut radyoterapisinin (SBRT) oligo-ilerlemeden sonra antiandrojen tedavisine devam eden metastatik kastrasyona dirençli prostat kanserli hastalarda birinci basamakta sağkalım üzerindeki etkilerini araştırmayı amaçladı. Gereç ve yöntem: Birinci basamakta abirateron veya enzalutamid ile tedavi edilen 57 metastatik kastrasyon dirençli (serum testosteron <50 ng/dl) prostat kanseri hastası retrospektif olarak analiz edildi. Görüntülemede ≤3 lezyon olarak tanımlanan oligo- progresif hastalığı olan 39 hasta aynı antiandrojen tedavisine devam edilerek SBRT aldı. Bulgular: Medyan yaş 70 (dağılım 40-85) idi. Kastrasyona duyarlı ortamda, hastaların 27’si (%47,4) dosetaksel almıştır. Oligo-progresif metastatik bölgeler 21 (%52,3) hastada kemik, 6 (%15,3) hastada lenf nodu ve 12 (%30,9) hastada visseral metastaz olarak saptandı. Abirateron ve enzalutamid sırasıyla %47,4, %52,6 hastada tercih edildi. SBRT alan ve almayan hastalarda 12 aylık progresyonsuz sağkalım (PFS) %79,0 ve %88,9 idi (p<0,001). Otuz beş (%61,4) hastada SBRT ile ilişkili derece 1-2 toksisite gözlendi. SBRT ayrıca PFS için bağımsız bir risk faktörüydü (p=0,007, HR:15,7; %95 GA 2,05-118,7). Visseral metastazlar, izole kemik metastazları, anti-androjen tedavi seçimi ve Eastern Cooperative Oncology Group (ECOG) performans skalası varlığı, PFS ile istatistiksel olarak anlamlı değildi. SBRT’nin genel sağkalım üzerinde hiçbir etkisi olmamıştır. Sonuç: Oligo-progresyon durumunda tedaviyi değiştirmeden metastaza yönelik SBRT ile tedavi edilen hastalarda sağkalım sonuçları daha kötüydü. Bu nedenle, aynı antiandrojen tedavisine devam edilerek metastaza yönelik SBRT’ye sadece seçilmiş vakalarda öncelik verilmelidir.

Anahtar Kelimeler

Stereotaktik vücut radyoterapisi, abiraterone, enzalutamide, kastrasyona dirençli prostat kanseri

Kaynakça

• 1. Cancer Research UK 2020; Available at: https://www. cancerresearchuk.org/about-cancer/prostate-cancer/risks-causes google scholar
• 2. Mottet N, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on prostate cancer-2020 update. part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 2021;79(2):243-62. [CrossRef] google scholar
• 3. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 2017; 377(4):352-60. [CrossRef] google scholar
• 4. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014;371(5):424-33. [CrossRef] google scholar
• 5. Scher HI, Fizazi K, Saad F, Taplin M-E, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367(13):1187-97. [CrossRef] google scholar
• 6. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364(21):1995-2005. [CrossRef] google scholar
• 7. Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase II randomized trial. J Clin Oncol 2020;38(25):2830-8. [CrossRef] google scholar
• 8. Phillips R, Shi WY, Deek M, Radwan N, Lim SJ, Antonarakis ES, 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):650-9. [CrossRef] google scholar
• 9. Lohaus F, Zophel K, Lock S, Wirth M, Kotzerke J, Krause M, et al. Can local ablative radiotherapy revert castrationresistant prostate cancer to an earlier stage of disease? Eur Urol 2019;75(4):548-51. [CrossRef] google scholar
• 10. Triggiani L, Mazzola R, Magrini SM, Ingrosso G, Borghetti P, Trippa F, et al. Metastasis-directed stereotactic radiotherapy for oligoprogressive castration-resistant prostate cancer: a multicenter study. World J Urol 2019;37(12):2631-7. [CrossRef] google scholar
• 11. Valeriani M, Marinelli L, Macrini S, Reverberi C, Aschelter AM, De Sanctis V, et al. Radiotherapy in metastatic castration-resistant prostate cancer patients with oligoprogression during abiraterone-enzalutamide treatment: a mono-institutional experience. Radiat Oncol 2019;14(1):205. [CrossRef] google scholar
• 12. Moyer CL, Phillips R, Deek MP, Radwan N, Ross AE, Antonarakis ES, et al. Stereotactic ablative radiation therapy for oligometastatic prostate cancer delays time-tonext systemic treatment. World J Urol 2019;37(12):2623-9. [CrossRef] google scholar
• 13. Deek MP, Taparra K, Phillips R, Velho PI, Gao RW, Deville C, et al. Metastasis-directed therapy prolongs efficacy of systemic therapy and improves clinical outcomes in oligoprogressive castration-resistant prostate cancer. Eur Urol Oncol 2021;4(3):447-55. [CrossRef] google scholar
• 14. Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, 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):446-53. [CrossRef] google scholar
• 15. Berghen C, Joniau S, Ost P, Poels K, Everaerts W, Decaestecker K, et al. progression-directed therapy for oligoprogression in castration-refractory prostate cancer. Eur Urol Oncol 2021;4(2):305-9. [CrossRef] google scholar
• 16. Ingrosso G, Detti B, Fodor A, Caini S, Borghesi S, Triggiani L, et al. Stereotactic ablative radiotherapy in castrationresistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy. Clin Transl Oncol 2021;23(8):1577-84. [CrossRef] google scholar
• 17. Patel PH, Tunariu N, Levine DS, de Bono JS, Eeles RA, Khoo V, et al. Oligoprogression in metastatic, castrate-resistant prostate cancer-prevalence and current clinical practice. Front Oncol 2022;17;12:862995. [CrossRef] google scholar
• 18. Rogowski P, Roach M 3rd, Schmidt-Hegemann NS, Trapp C, von Bestenbostel R, Shi R, et al. Radiotherapy of oligometastatic prostate cancer: a systematic review. Radiat Oncol 2021;16(1):50. [CrossRef] google scholar
• 19. Zilli T, Achard V, Dal Pra A, Schmidt-Hegemann N, JereczekFossa BA, Lancia A, et al. Recommendations for radiation therapy in oligometastatic prostate cancer: An ESTROACROP Delphi consensus. Radiother Oncol 2022;176:199- 207. [CrossRef] google scholar
• 20. Detti B, D’Angelillo RM, Ingrosso G, Olmetto E, Francolini G, Triggiani L, et al. Combining abiraterone and radiotherapy in prostate cancer patients who progressed during abiraterone therapy. Anticancer Res 2017;37 (7):3717-22. [CrossRef] google scholar