Radiotherapy in metastatic castration resistant prostate cancer patients with oligo-progression during abiraterone-enzalutamide treatment: a mono-institutional experience

Abstract

BackgroundSome patients experience oligo-progression during androgen receptor targeted therapy (ARTT) treatments. This progression might not indicate a real systemic drug resistance, but a selective monoclonal resistance. With the aim to delay the start of new line treatments we treated oligo-progressive sites with radiotherapy.MethodsFrom June 2011 to Febrary 2019, 29 consecutive metastatic castration resistant prostate cancer (mCRPC) patients were submitted to radiotherapy for oligo-progression (1–3 sites) during ARTT for a total of 37 lesions treated. Thirty-one (83.8%) lesions were treated with conformal radiotherapy and 6 (16.2%) with stereotactic radiotherapy. After radiotherapy all patients continued ARTT.ResultsMedian OS (calculated from ARTT start) was 46,6 months (range 4.4–97.5 months), 2 and 3-year OS were 82.8 and 70.7%, respectively. Median PFS was 18,4 months (range 4.4–45.3 months), 2 and 3-year PFS were 38.3 and 8.5%, respectively. Median overall duration of ARTT treatment was 14.8 months (range 4.4–45.3 months) and median duration of ARTT after radiotherapy was 4.6 months (range 1–33.8 months). Patients submitted to radiotherapy > 6 months from the start of ARTT presented a better PFS (p < 0.001) and a trend toward a better OS (p = 0.101). None patient presented RT and drug related toxicities.ConclusionsRadiotherapy of oligoprogressive sites may prolong the duration of disease control under ARTT in mCRPC patients with a possible delay in the start of new line treatment. Patients progressing within 6 months from the start of ARTT did not benefit from this approach. More studies are necessary to confirm our results and to evaluate other prognostic factor in order to select patients with high benefit from this approach.

Impact of Time to Castration Resistance on Cytoreductive Radiotherapy in Metastatic Castration-Resistant Prostate Cancer

“…However, mCRPC represents a heterogeneous cohort, and an intermediate state between localized and widespread disease may exist in certain patients with mCRPC. Some retrospective studies showed that radiotherapy delayed disease progression in patients with oligometastatic CRPC (17,(25)(26)(27). Similarly, in the present study, CRT was associated with improved PSA response and OS in mCRPC, indicating that patients with limited metastasis might benefit from local therapy against most or all of metastatic lesions.…”

“…Increasing evidence indicates that cytoreductive therapy is associated with survival benefits in many metastatic solid tumors, such as metastatic renal cell carcinoma (13,14), metastatic colon cancer (15), and metastatic hormone-sensitive prostate cancer (16). Recently, a retrospective study with a small sample size (n = 29) showed that radiotherapy directed at oligo-progressive sites might prolong the duration of disease control in patients with mCRPC treated with ARATAs (17). However, data to evaluate the value of CRT in patients with mCRPC is still lacking.…”

Cytoreductive Radiotherapy Combined with Abiraterone in Metastatic Castration-Resistance Prostate Cancer: A Single Center Experience

“…New-generation ARAT can result in downregulation of expression of the DNA repair genes, thereby potentiating the effect of ionizing radiation [21]. In clinical studies, a delay of disease progression has been observed after delivering radiotherapy to mCRPC patients treated with abiraterone [22][23][24]. Similarly, our study showed that the survival bene t was most pronounced if cRT was combined with abiraterone.…”

“…In contrast, cRT for mCRPC seems less attractive because the value of local therapy at such a late stage is questionable. Several retrospective studies show that radiotherapy to oligoprogressive sites could delay disease progression in mCRPC [22,24,28]. In the study by Yildirim et al, prolonged abiraterone use was also observed in mCRPC patients receiving prostate-directed therapy, but no signi cant improvement of OS was found (24.1 vs. 21.4 months; P = 0.08) [23].…”

<p>Long Non-Coding RNA GAS5 Suppresses Tumor Progression and Enhances the Radiosensitivity of Prostate Cancer Through the miR-320a/RAB21 Axis</p>

“…1 Radiotherapy can prolong the control duration of cancer as a frequently adjunctive therapy of surgical surgery and chemotherapy in PCa treatments. 2,3 The appearance of radioresistance severely limits the therapeutic efficacy of radiotherapy, having detrimental influence on the treatment and prognosis of PCa patients. 4 It is essential to enhance the radiosensitivity in PCa to develop the optional selective treatment of PCa.…”