Androgen Receptor Targeted Therapy + Radiotherapy in Metastatic Castration Resistant Prostate Cancer

Abstract

ObjectivesTo investigate whether radiotherapy as metastasis-directed therapy (MDT) on oligo-progressive sites in metastatic castration-resistant prostate cancer (mCRPC) patients during treatment with androgen receptor-targeted therapy (ARTT) may lead to control resistant lesions, prolonging ARTT. We analysed progression free survival, overall survival and prognostic parameters that can identify patients that best suit to this approach.Patients and MethodsRetrospective analysis of a total of 67 lesions in 42 mCRPC patients treated with ablative or palliative RT to oligoprogressive lesions during ARTT. Twenty-eight patients (67%) underwent ARTT with Abiraterone acetate and 14 patients (33%) underwent ARTT with Enzalutamide. Median time between the start of ADT and ARTT beginning was 50.14 months (range 3.37-219 months). We treated 58 lesions (87%) with 3D conformal radiotherapy (3DCRT) and nine lesions (13%) with stereotactic body radiotherapy (SBRT). The Kaplan Meier method was used to assess the median overall survival (OS) and the progression-free survival (PFS).ResultsMedian follow-up was 28 months (range 3-82 months). Median OS was 32.5 months (95% CI 25.77-39.16), 1 and 2-year OS were 71.6% and 64.1%, respectively. Median PFS was 19,8 months (95% CI 11.34–28.31), 1 and 2-year PFS were 67.2% and 47.4%, respectively. Median OS for patients that underwent radiotherapy before 6 months from the start of ARTT was 23.4 months (95% CI 2.04-44.89) and 45.5 months (95% CI 31.19-59.8) for patients that underwent radiotherapy after 6 months (p = 0.009).ConclusionLocal ablative radiation therapy directed to progressive metastasis is a non-invasive, well tolerated treatment with efficacy on prolonging clinical benefit of systemic therapies with ARTT. Patients who underwent RT >6 months from the start of ARTT presented a statistically better OS and PFS compared with patients who underwent radiotherapy <6 months from the start of ARTT.

Megestrol Acetate for Heavily Pretreated Metastatic Castration-Resistant Prostate Cancer: An Old Answer for a New Problem

“…Our clinical case also showed the importance of combining local and systemic treatments in the management of mPC to control oligoprogression sites and prolong NEST-free survival. Although this combined strategy does not represent a standard of care, several studies showed improvements in local control, progression-free survival and OS, preserving the current therapy and delaying the start of a new systemic therapy [9, 10].…”

Stereotactic body radiotherapy in oligoprogressive metastatic castration-resistant prostate cancer during abiraterone or enzalutamide

“…Abiraterone acetate (AA) is a selective inhibitor of cytochrome P450 17α-hydroxylase/17,20 lyase (CYP17), interfering with androgen biosynthesis, while enzalutamide is a second-generation nonsteroidal AR direct inhibitor. 7,8…”

“…Radiotherapy (RT) is the most feasible, safest and easiest local treatment used for this purpose. 7,13…”

“…However, sometimes disease progression affects only a few metastatic sites, suggesting it does not represent a systemic drug-resistance. 7,8,13 This kind of resistance may be overcome in the sites of progression with metastasis-directed therapy (MDT). Radiotherapy (RT) is the most feasible, safest and easiest local treatment used for this purpose.…”

“…[4][5][6] Abiraterone acetate (AA) is a selective inhibitor of cytochrome P450 17α-hydroxylase/17,20 lyase (CYP17), interfering with androgen biosynthesis, while enzalutamide is a second-generation nonsteroidal AR direct inhibitor. 7,8 Four randomized clinical trials (COU-AA-302 and COU-AA-301 for abiraterone, PREVAIL and AFFIRM for enzalutamide) have investigated ARTAs in mCRPC, both in chemotherapy-naive and pretreated patients respectively, they are able to significatively impact OS safely. [9][10][11][12] Unfortunately, ARTAs fail because of the development of mechanisms of resistance that lead to disease progression.…”