Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients with No Progression and with No More than Five Residual Metastatic Lesions Following First-Line Systemic Therapy: A Retrospective Analysis

Abstract

Local consolidative radiotherapy in the treatment of metastatic malignancies has shown promising results in several types of tumors. The objective of this study was to assess consolidative radiotherapy to the bladder and to residual metastases in metastatic urothelial bladder cancer with no progression following first-line systemic therapy. Materials/methods: Patients who received first-line therapy for the treatment of metastatic urothelial bladder cancer (mUBC) and who were progression-free following treatment with no more than five residual metastases were retrospectively identified through the database of four Comprehensive Cancer Centers, between January 2005 and December 2018. Among them, patients who received subsequent definitive radiotherapy (of EQD2Gy > 45Gy) to the bladder and residual metastases were included in the consolidative group (irradiated (IR) group), and the other patients were included in the observation group (NIR group). Progression-free survival (PFS) and overall survival (OS) were determined from the start of the first-line chemotherapy using the Kaplan–Meier method. To prevent immortal time bias, a Cox model with time-dependent covariates and 6-month landmark analyses were performed to examine OS and PFS. Results: A total of 91 patients with at least stable disease following first-line therapy and with no more than five residual metastases were analyzed: 51 in the IR group and 40 in the NIR group. Metachronous metastatic disease was more frequent in the NIR group (19% vs. 5%, p = 0.02); the median number of metastases in the IR group vs. in the NIR group was 2 (1–9) vs. 3 (1–5) (p = 0.04) at metastatic presentation, and 1 (0–5) vs. 2 (0–5) (p = 0.18) after completion of chemotherapy (residual lesions), respectively. Two grade 3 toxicities (3.9%) and no grade 4 toxicity were reported in the IR group related to radiotherapy. With a median follow up of 85.9 months (95% IC (36.7; 101.6)), median OS and PFS were 21.7 months (95% IC (17.1; 29.7)) and 11.1 months (95% IC (9.9; 14.1)) for the whole cohort, respectively. In multivariable analysis, consolidative radiotherapy conferred a benefit in both PFS (HR = 0.49, p = 0.007) and OS (HR = 0.47, p = 0.015) in the whole population; in the landmark analysis at 6 months, radiotherapy was associated with improved OS (HR = 0.48, p = 0.026), with a trend for PFS (HR = 0.57, p = 0.082). Conclusion: Consolidative radiotherapy for mUBC patients who have not progressed after first-line therapy and with limited residual disease seems to confer both OS and PFS benefits. The role of consolidative radiotherapy in the context of avelumab maintenance should be addressed prospectively.

Stereotactic body radiation therapy is beneficial for a subgroup of patients with urothelial cancer and solitary metastatic disease: a single institution real-world experience

“…A systematic review and meta-analysis including available reports addressing SBRT in patients with oligometastatic and oligoprogressive urothelial cancer identi ed 6 studies with 158 patients included in total (11). The publications included in the meta-analysis come from small and retrospective studies with signi cant variation regarding inclusion criteria, assessment of outcomes, etc (12)(13)(14)(15)(16)(17), making a comparison between these studies challenging. This meta-analysis showed that most patients were older males with primary tumours in the urinary bladder, in agreement with our data, and as expected for urothelial cancer (11).…”

“…Only 36% had received palliative systemic treatment before SBRT. Primary metastatic disease, n (%) 5 (13) Palliative systemic treatment pre-SBRT, n (%) 14 (36)…”

Definitions, outcomes and perspectives for oligometastatic bladder cancer: towards a standardized terminology

“…Aboudaram et al . [36 ▪ ] reported that consolidative radiotherapy to the primary and the metastatic sites (up to five metastases allowed, nonprogressive after induction chemotherapy) was associated both with PFS and OS benefit, with severe RT-related toxicities limited to 2.3%.…”

Radiotherapy in metastatic bladder cancer

“…Specifically for bladder or urothelial cancer, a few retrospective studies (Table 2 ) have reported clinical outcomes with SABR for oligometastases [ 27 – 32 ]. Lymph nodes were the most commonly treated lesions in these case series [ 27 – 29 , 31 ]. A retrospective case series of 91 patients with up to 5 metastases reported improved overall survival (HR 0.48, p = 0.026) and progression free survival at 6 months (HR 0.57, p = 0.083) for those who received consolidative radiotherapy to the bladder and residual metastases compared with those in an observation group, with local nodes treated most commonly (64%) [ 29 ].…”

“…Lymph nodes were the most commonly treated lesions in these case series [ 27 – 29 , 31 ]. A retrospective case series of 91 patients with up to 5 metastases reported improved overall survival (HR 0.48, p = 0.026) and progression free survival at 6 months (HR 0.57, p = 0.083) for those who received consolidative radiotherapy to the bladder and residual metastases compared with those in an observation group, with local nodes treated most commonly (64%) [ 29 ]. Another multicentre retrospective analysis of 61 patients with ≤ 5 metastases at diagnosis reported on outcomes after SABR to total 82 lesions, commonest being lung (40%) [ 30 ].…”