Metastasis-directed radiotherapy for oligometastatic urothelial carcinoma of the bladder and upper tract

Abstract

Background

Metastasis-directed therapy (MDT) for oligometastatic cancer is utilized for genitourinary malignancies including prostate and kidney cancers. Clinical research on MDT for urothelial carcinoma (UC) remains sparse, especially as systemic therapy advances have improved outcomes.

Objective

We investigated the role of MDT, specifically radiotherapy, for patients with oligometastatic bladder or upper-tract UC.

Methods

Data were collated on patients with metastatic UC with 5 or fewer metastatic sites undergoing MDT with ablative radiotherapy with or without preceding systemic therapy during January 2016 to July 2024. Endpoints were progression-free survival (PFS), and overall survival (OS). Cox proportional hazards analysis was conducted to determine the covariates associated with these endpoints.

Results

Fifty-two patients were included. Most were men (67%). Median age was 68 years (interquartile range, 62–78). Most had bladder primary tumors (79%). Patients had a median of 1 metastatic site. Most received ≥2 lines of systemic therapy before MDT (60%), whereas 8% received no systemic therapy before MDT. MDT was delivered to all metastases in 71% of cases, whereas the remaining cases (29%) had MDT delivered to select sites. Median follow-up from the diagnosis of metastasis was 32 months (interquartile range, 23–42). Median PFS and OS were 19 months (95% CI, 15–24) and 42 months (95% CI, 24–60), respectively.

Conclusions

MDT may serve as an effective adjunct to systemic therapy to improve outcomes of oligometastatic and oligoprogressive UC.

Keywords

urothelial carcinoma bladder cancer upper tract urothelial carcinoma metastasis directed therapy radiation oligometastatic

Introduction

Metastatic urothelial carcinoma (UC), including bladder and upper-tract cancers, pose significant challenges owing to historically limited treatment options.^1,2 Current practice is to treat metastatic UC with sequential lines of systemic therapy indefinitely, with effectiveness typically waning with subsequent lines and the burden of toxic effects increasing. Metastatic disease exists on a spectrum with patients harboring a limited metastatic burden, i.e., oligometastatic disease defined as up to 5 sites, exhibiting distinct behavior compared to polymetastatic burden.³

Recent advances in systemic therapies, including immunotherapy and antibody-drug conjugates, have transformed the therapeutic landscape, improving overall survival (OS) for patients. As the efficacy of systemic therapy has improved and micrometastatic disease is addressed, the role of local therapies including metastasis-directed therapy (MDT), targeting macrometastases has garnered interest for certain cancers in the oligometastatic setting, including UC, other genitourinary malignancies such as prostate and renal-cell cancers, and non–small-cell lung cancer.⁴ MDT, which includes stereotactic body radiation therapy (SBRT), focal ablation, and surgery, aims to achieve durable local control and prevent seeding of new distant metastases from oligometastatic sites. Although MDT has been well studied in prostate and kidney cancers,^5,6 its role in oligometastatic UC remains undefined.

In this study, we investigated the role of MDT, specifically radiotherapy (RT), for patients with oligometastatic or oligoprogressive UC of the bladder and upper tract.

Materials and methods

Patients

Data from the clinical records of patients with radiographically and histologically confirmed metastatic UC of the bladder or upper tract who received MDT with ablative radiotherapy during January 2016 to July 2024 were retrospectively identified and included for analysis. Patients’ disease was categorized based on recent consensus definitions for oligometastatic bladder cancer.⁷ Synchronous oligometastasis was defined as 5 or fewer metastatic lesions present at or within 6 months of diagnosis. Oligoprogression was defined as 5 or fewer metastatic lesions progressing in the setting of otherwise stable or responding disease on systemic therapy. A metastatic site was defined as a distinct anatomical lesion. Multiple metastases within the same organ were counted as separate sites if they were anatomically distinct. For lymph node metastases, all nodes within the same anatomic basin were counted as a single site. Distinct non-contiguous nodal basins were counted separately. Institutional review board approval (PA17-0577) was obtained prior to study initiation, and informed consent was waived given the study's retrospective nature.

Procedures

RT dose and technique were determined by the treating radiation oncologist. The highest possible biologic RT dose was delivered to the tumor, respecting the normal tissue tolerance of surrounding organs. SBRT delivered over 5 fractions or fewer was the preferred technique; however, hypofractionated intensity-modulated or volumetric arc RT was allowed at the discretion of the treating radiation oncologist if SBRT was deemed unsafe. Four-dimensional computed tomography (CT) simulation was used for lesions in the lung or upper abdomen to assess tumor motion, and breath-hold gating technique was used when the tumor motion exceeded 1 cm. Patients received daily image guidance with cone-beam CT, CT-on-rails, or magnetic resonance imaging–guidance using a Unity MR-Linac (Elekta, Stockholm, Sweden).

Baseline staging included chest, abdomen, pelvis baseline imaging with CT fludeoxyglucose F-18 positron emission tomography, magnetic resonance imaging or any combination thereof with brain imaging as indicated. Brain imaging was performed at least annually per institutional protocol and more frequently per standard surveillance guidelines for patients with a history of CNS metastases. Staging methods were determined by the treating physician according to the clinical scenario. The chosen baseline imaging was used for future reassessments of the disease status at follow-up visits, which occurred at least every 3 months for the first year after MDT, then every 3 to 6 months thereafter per the treating physician as a part of our institutional standard surveillance. Urologic oncology multidisciplinary review was conducted by videoconference weekly to determine the role of MDT for patients with metastatic UC. All initial and follow-up imaging findings were reviewed by radiologists or nuclear medicine specialists using the Response Evaluation Criteria in Solid Tumors or Positron Emission Tomography Response Criteria in Solid Tumors criteria.⁸ The most common mode of follow-up imaging was CT and bone scintigraphy, with selective use of FDG-PET. Sites of progression were biopsied if radiographic evidence was equivocal and/or for additional molecular testing. Adverse events were assessed at baseline and at each follow-up visit using the Common Terminology Criteria for Adverse Events (v. 4.0) and extracted from the electronic medical record.

Statistical analysis

Categorical variables were evaluated as frequencies and percentages, whereas continuous variables were evaluated as medians and ranges. To evaluate progression-free survival (PFS) and overall survival (OS), the Kaplan-Meier method was used, and comparisons were made using the log-rank test with corresponding P values reported. All time-to-event analyses were performed from RT completion to the event or last follow-up. Local recurrence was characterized by radiographic evidence of recurrent disease within the MDT radiation field. Cox regression analysis was used to explore whether specific factors were significantly associated with survival outcomes. These factors were age, sex, histology, primary disease site (bladder vs. upper tract), disease state (oligometastatic vs. oligoprogressive), the number of prior lines of systemic therapy, the number of disease sites, the presence of brain metastases, whether all sites were treated with MDT, and adjuvant therapy. Due to the modest sample size and limited number of events, only univariate Cox regression was performed to reduce the risk of overfitting. Multivariable modeling was not conducted given the potential for instability with too many covariates relative to the number of outcomes. Two-sided tests were conducted, and statistical significance was defined as a p value below 0.05. All analyses were conducted using SAS JMP Pro software, version 15.0.0 (SAS Institute Inc., Cary, NC).

Results

Patient characteristics

Overall, 52 patients were included in the final analysis, comprising 125 treated sites. Most patients were men (67%); the median age was 68 years (interquartile range, 62–78). Most patients had bladder primary tumors (79%), with the remaining patients having upper-tract-ureter or renal-pelvis primary tumors. By histology, 44 patients (85%) had pure UC, while 8 patients had UC with variant subtype features including 4 patients with neuroendocrine features, 2 patients with squamous features, 1 patient with glandular features, and 1 patient with sarcomatoid features. Seventeen patients (33%) had oligometastatic disease, and 35 patients (67%) had oligoprogressive disease. Patients had a median of 1 involved metastatic site, with 87% of patients having 1–3 involved sites and 13% having >3 involved sites. Treatment to a progressive primary site was performed in 5 patients (10%) as a component of MDT. The most common sites of metastatic disease were non-regional lymph nodes (37%), bone including spine (31%), lung (31%), brain (19%), and liver (10%) (Figure 1). Table 1 summarizes patients’ baseline characteristics.

Figure 1.

Sites of metastatic disease.

Table 1.

Baseline characteristics (n = 52).

Characteristic	No.	%
Median Age (years)	68
Gender
Male	35	67%
Female	17	33%
Histology
UC	44	85%
UC subtype with variant histology	7	15%
Site of Primary
Bladder	41	79%
Upper Tract	11	21%
Sites of metastatic disease
Non-regional lymph nodes	19	37%
Bone	16	31%
Lung	16	31%
Brain	10	19%
Liver	5	10%
Lines of therapy prior to MDT
0	4	8%
1	17	33%
2	16	31%
3+	15	29%
Sites of Disease
1	29	56%
2	11	21%
3	5	10%
4–5	7	13%
MDT to all sites
No	15	29%
Yes	37	71%

MDT: metastasis-directed therapy; UC: urothelial carcinoma.

There were 8% of patients received no systemic therapy prior to MDT. The remaining patients received one line (33%), two lines (31%), or three or more lines (29%) of prior systemic therapy. Overall, 60% of patients had received two or more lines of therapy before undergoing MDT. The most commonly used systemic therapy regimens were dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (21%); gemcitabine and cisplatin (20%); pembrolizumab (15%); and enfortumab vedotin (± pembrolizumab) (12%). MDT was delivered to all metastatic sites in 71% of patients, whereas MDT was delivered to only select sites in the remaining patients (29%). The most common MDT dose was 30 Gy in 3 fractions (21%), followed by 50 Gy in 4 fractions (17%). Systemic therapy was administered to 22 patients (42%) after the completion of MDT, whereas the remaining 58% of patients underwent only surveillance imaging. The most commonly used adjuvant systemic therapy was immune checkpoint inhibition alone in 12 patients (23%), followed by enfortumab vedotin (EV) with or without pembrolizumab in 8 patients (15%), and chemotherapy in 2 patients (4%).

Outcomes

Median follow up from diagnosis of metastatic disease was 32 months (interquartile range, 23–42). Median PFS for the entire cohort was 19 months (95% confidence interval [CI], 15–24 months) (Figure 2). The PFS rates at 1 and 2 years were 76% (95% CI, 63%–85%) and 43% (95% CI, 31%–59%), respectively. Median OS for the entire cohort was 42 months (95% CI, 24–60 months) (Figure 3). The OS rates at 1 and 2 years were 88% (95% CI, 78%–96%) and 65% (95% CI, 51%–76%), respectively. At last follow-up, 29 patients were alive (56%), 13 of whom (25%) were not receiving active systemic therapy. The swimmer plot in Figure 4 shows timetables for all included patients in relation to timing of MDT in their disease course. 10 patients (19%) were alive beyond 24 months and among these patients, no brain metastases were present, and all received MDT to all metastatic sites. Regarding adverse events, 22 patients (42%) experienced a grade 2 or lower adverse event from MDT, the most common of which was fatigue and/or pain at the site of RT. No patients experienced a grade 3 or higher adverse event.

Figure 2.

Progression-free survival and overall survival Kaplan-Meier analyses.

Figure 3.

Progression-free survival and overall survival Kaplan-Meier analyses.

Figure 4.

Swimmer's plot of MDT and outcomes.

Local recurrence occurred in only 2 patients (4%), both of which were located in pelvic bones treated with MDT. Distant recurrence predominated as the primary mode of recurrence (96%). On univariate analysis, having 2 or more sites of metastasis at time of MDT was significantly associated with worse PFS (HR 2.99 (95% CI, 1.30–6.86), p = 0.01), whereas treatment of all known metastatic sites with MDT, as opposed to treatment of only select lesions, was associated with improved PFS (HR 0.43; 95% CI, 0.20–0.92; p = 0.032). The presence of brain metastases at the time of MDT was significantly associated with worse OS (HR 3.4 (95% CI, 1.46–8.03), p = 0.005). All univariate analyses are reported in Table 2.

Table 2.

Univariate analyses.

	Cox Univariate Analysis PFS		Cox Univariate Analysis OS
	HR (95% CI)	P value	HR (95% CI)	P value
Age	0.98 (0.95–1.01)	0.22	0.99 (0.96–1.03)	0.88
Histology
Urothelial	Reference		Reference
Variant subtype	0.95 (0.33–2.73)	0.92	1.25 (0.43–3.69)	0.68
Primary
Bladder	Reference		Reference
Upper Tract	0.98 (0.43–2.24)	0.96	0.91 (0.36–2.32)	0.85
Disease State
Oligometastatic	Reference		Reference
Oligoprogressive	1.05 (0.46–2.38)	0.91	0.64 (0.27–1.53)	0.32
Prior lines of therapy
0–1	Reference		Reference
2+	1.28 (0.58–2.85)	0.54	1.01 (0.43–2.40)	0.98
Sites of disease at MDT
1	Reference		Reference
2+	2.99 (1.30–6.86)	0.01*	1.68 (0.72–3.92)	0.23
All sites treated w MDT
No	Reference		Reference
Yes	0.43 (0.20–0.92)	0.032*	0.64 (0.27–1.54)	0.32
Enfortumab Vedotin Prior to RT
No	Reference		Reference
Yes	0.44 (0.13–1.47)	0.18	0.41 (0.09–1.74)	0.23
Adjuvant therapy post MDT
No	Reference		Reference
Yes	1.81 (0.85–3.87)	0.12	0.51 (0.57–3.1)	0.51

CI: confidence interval; HR: hazard ratio; MDT: metastasis-directed therapy; OS: overall survival; PFS: progression free survival; UTUC: upper tract urothelial carcinoma.

*Significant association.

Discussion

Our study demonstrated that MDT may be associated with favorable outcomes when integrated with systemic therapy in well-selected patients with oligometastatic and oligoprogressive UC, and, to our knowledge, is the largest series of patients who received MDT and modern systemic therapy including immunotherapy and antibody-drug conjugates. Median PFS was 19 months at last follow-up, local control was 96% in-treated lesions, and no patients experienced high grade toxicity from MDT. Distant metastases were the predominant mode of recurrence underscoring the importance of systemic therapy as a complementary approach to MDT. These findings highlight the potential of MDT to improve outcomes for select patients with a limited metastatic burden.

Historically, MDT has been used primarily in prostate and kidney cancers, in which systemic therapies are well-established and effective, paving the way for local therapies to address residual macroscopic disease in additional cancers.^4–6^,9 However, unlike these more indolent genitourinary cancers, UC can present with fulminant metastatic disease that warrants immediate initiation of systemic therapy and complicates the upfront integration of MDT. Recent population-level studies have further clarified the prognostic implications of metastatic burden and evolving treatment paradigms in metastatic urothelial carcinoma (mUC). Di Bello et al. analyzed SEER data and demonstrated that increasing number of metastatic organ sites was independently associated with worse overall survival in systemic therapy–treated mUC patients, with brain metastases conferring particularly poor outcomes even in the setting of solitary metastasis.¹⁰ These findings complement our observations that patients with limited metastatic burden, particularly those with all sites amenable to MDT, may experience favorable survival outcomes.

The delayed adoption of MDT in UC can also be attributed to the lack of robust systemic options; the historical OS for metastatic UC treated with cytotoxic chemotherapy alone is approximately 12 to 14 months.^11,12 However, recent advances in novel systemic therapies have significantly improved OS in metastatic UC, enabling the integration of MDT into oncologic management.^13–15 Trends in systemic therapy use highlight a growing adoption of immunotherapy and targeted agents over time, which may be improving outcomes at a population level.¹⁶ For example, Powles et al. observed a precedent-setting 31-month median OS in patients with metastatic UC who were treated with enfortumab vedotin and pembrolizumab.¹³ Our observed OS of 42 months after MDT compares favorably with this and other OS results associated with metastatic UC, especially considering 60% of patients in our cohort were heavily pretreated with at least 2 lines of systemic therapy before receiving MDT.^{2,14,15,17,18} While our study predates widespread use of some of these agents, it underscores the importance of integrating MDT with evolving systemic treatment strategies, particularly as the metastatic burden and site-specific prognostic factors gain clarity.

The outcomes we observed with MDT is supported by similar studies. In a retrospective review, MDT was reported to have durable disease control with limited toxic effects in carefully selected patients with oligometastatic UC.¹⁹ Similarly, population-based studies reported improved survival outcomes associated with aggressive local therapies, including RT, in patients with metastatic UC.²⁰ Our findings are supported by a recent systematic review and meta-analysis by Longo et al., which evaluated MDT in oligometastatic UC and reported that MDT was associated with delayed disease progression and potentially improved PFS, though the authors acknowledged the limited quality of available evidence and emphasized the need for prospective trials.²¹ In comparison with the aforementioned study, our series demonstrates higher PFS and OS, which may reflect differences in patient selection, systemic therapy use, and the proportion of patients receiving consolidation to all metastatic sites.

Prior to our current study, one multicenter retrospective study examined the role of SBRT in oligometastatic bladder cancer and included patients who received chemotherapy before or during SBRT and found a median PFS of 10 months and OS of 25.6 months.²² However, this study did not incorporate immunotherapy or more novel antibody-drug conjugates, underscoring the importance of our inclusion of more modern systemic therapies in our study, which resulted in a longer median PFS of 19 months. Another large retrospective study reviewed 52 patients treated with MDT after radical cystectomy and reported a median PFS of 10 months; however, 60% of RT was administered with palliative intent.²³ In addition, nearly a third (27%) of the patients did not receive upfront chemotherapy before MDT, in contrast to the 8% of patients in our cohort who had no prior systemic therapy, emphasizing the importance of systemic therapy as the backbone to MDT integration.²¹ These outcomes highlight how advancements in systemic therapies and improved patient selection can lead to notably better outcomes for patients treated with MDT.

We identified factors that could potentially guide patient selection for MDT: Total MDT consolidation was associated with improved PFS, the presence of 2 or more metastatic sites was associated with worse PFS, and the presence of brain metastases was associated with worse OS. Improved outcomes in patients with only a single site of metastasis were also observed in other oligometastatic UC case series, which suggests the classical definition of oligometastasis of 5 or fewer sites may be too lenient for UC.^22,24 A consensus committee of European uro-oncologists suggested most studies of oligometastatic UC used 3 metastatic sites as the cutoff for oligometastasis, indicating that 3 or fewer sites of metastasis may serve as a more appropriate definition for UC.⁷ In addition, the observed PFS benefit with the total consolidation of all metastatic sites with MDT is similar to the findings of the ORIOLE trial on oligometastatic prostate cancer and may highlight the need to address all sites of UC metastasis when MDT is considered.⁹

Although our findings are promising, they should be interpreted within the context of our study's limitations. Given the retrospective nature of our study and lack of multivariable analysis due to sample size constraints, our results should be interpreted as hypothesis-generating with a need for prospective, randomized studies to validate our findings. Our univariate analyses included multiple covariates, which may introduce risk of overfitting despite being exploratory. Larger datasets are needed to support multivariable modeling and robust prognostic factor assessment. Additionally, the lack of a control cohort in our study prevents definitive conclusions regarding the comparative efficacy of MDT versus other treatment strategies, such as next-line systemic therapy and is prone to selection bias for MDT. However, novel systemic therapy such as EV with pembrolizumab was not associated with PFS or OS outcomes and warrants further exploration. Ongoing prospective studies, such as the EXTEND-OP randomized phase II basket trial (NCT06367972), are exploring the role of MDT in patients with oligoprogressive UC by randomizing these patients to continued systemic therapy with MDT or to next-line systemic therapy. This trial is assessing the benefit of MDT for oligoprogressive UC in prolonging the durability of systemic therapy and improving or maintaining patients’ quality of life.

Our study supports the integration of MDT along with systemic therapy for oligometastatic and oligoprogressive UC. MDT was safe, was well tolerated, exhibited high local control, and had favorable outcomes compared with those of historical literature. The integration of MDT with modern systemic therapies may improve survival outcomes in well-selected patients with oligometastatic UC. Prospective studies are needed to validate these findings and optimize the use of MDT in this evolving therapeutic landscape.

Footnotes

Acknowledgements

We thank Matthew Landry for the graphic design of the manuscript's figures. We thank Madison Semro, Associate Scientific Editor and Sarah Bronson, Scientific Editor, in the Research Medical Library at The University of Texas MD Anderson Cancer Center for editing this article.

ORCID iDs

Byron Lee

Comron Hassanzadeh

Ethnical approval and informed consent

This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The study was approved by the MD Anderson Internal Review Board (IRB) (Approval PA16-0577). All procedures performed in studies involving human participants were in accordance with ethical standard of the institutional review board. Informed consent was obtained for all individuals participants included in the study.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interest

The authors declared no potential conflicts of interest with respect to research, authorship, and/or publication of this article.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Due to privacy and ethical restrictions, raw data cannot be shared publicly but aggregated data supporting the conclusions of this article are included within the manuscript and its information files.

References

Mertens

Psutka

Mir

. Bladder cancer oligometastases — definition and treatment. Nature Reviews Urology 2023; 20: 701–702.

Powles

, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Engl J Med 2024; 390: 875–888.

Hellman

Weichselbaum

. Oligometastases. J Clin Oncol 1995; 13: 8–10.

Palma

, 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: 2830–2838.

Huynh

, et al. Review of prospective trials assessing the role of stereotactic body radiation therapy for metastasis-directed treatment in oligometastatic genitourinary cancers. Euro Urol Oncol 2023; 6: 28–38.

Tang

, et al. Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: a single-arm, single-centre, feasibility, phase 2 trial. Lancet Oncol 2021; 22: 1732–1739.

Bamias

Stenzl

Zagouri

, et al. Defining oligometastatic bladder cancer: a systematic review. Euro Urol Open Sci 2023; 55: 28–37.

Eisenhauer

, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228–247.

Phillips

, et al. Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer. JAMA Oncol 2020; 6: 650–659.

10.

Di Bello

, et al. Survival of metastatic urothelial carcinoma of urinary bladder according to number and location of visceral metastases. Clin Genitourin Cancer 2024; 22: 102139.

11.

von der Maase

, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2023; 41: 3881–3890.

12.

Rosenberg

, et al. Randomized Phase III trial of gemcitabine and cisplatin with bevacizumab or placebo in patients with advanced urothelial carcinoma: Results of CALGB 90601 (Alliance). J Clin Oncol 2021; 39: 2486–2496.

13.

Powles

, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med 2021; 384: 1125–1135.

14.

Grivas

, et al. Sacituzumab govitecan in combination with pembrolizumab for patients with metastatic urothelial cancer that progressed after platinum-based chemotherapy: TROPHY-U-01 cohort 3. J Clin Oncol 2024; 42: 1415–1425.

15.

Apolo

, et al. AMBASSADOR Alliance A031501: Phase III randomized adjuvant study of pembrolizumab in Muscle-Invasive and Locally Advanced Urothelial Carcinoma (MIUC) vs observation . 2025.

16.

Di Bello

, et al. Contemporary survival in metastatic bladder cancer patients: a population-based study. Int J Cancer 2024; 155: 1762–1768.

17.

Bajorin

, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med 2021; 384: 2102–2114.

18.

Mamede

, et al. Adjuvant immunotherapy in high-risk muscle-invasive urothelial cancer: An updated meta-analysis of randomized controlled trials. Clin Genitourin Cancer 2025; 23: 102288.

19.

Augugliaro

, et al.

Recurrent oligometastatic transitional cell bladder carcinoma: is there room for radiotherapy?

Neoplasma 2019; 66: 160–165.

20.

Grass

, et al. A population-based assessment of local therapy for De Novo oligometastatic urothelial carcinoma of the bladder. Int J Radiation Oncol*Biol*Phy 2021; 111: e259.

21.

Longo

, et al. Metastasis-directed radiation therapy with consolidative intent for oligometastatic urothelial carcinoma: A systematic review and meta-analysis. Cancers (Basel) 2022; 14: 2373.

22.

Franzese

, et al. Stereotactic body radiation therapy in the management of oligometastatic and oligoprogressive bladder cancer and other urothelial malignancies. Clin Oncol 2021; 33: 50–56.

23.

Miranda

, et al. Metastasis-directed radiation therapy after radical cystectomy for bladder cancer. Urol Oncol: Semin Orig Invest 2021; 39: 790.e1–790.e7.

24.

Kim

, et al. Pulmonary metastasectomy could prolong overall survival in select cases of metastatic urinary tract cancer. Clin Genitourin Cancer 2015; 13: e297–e304.