Adjuvant Radiotherapy for Upper Tract Urothelial Carcinoma: Systematic Review and Meta-Analysis

Abstract

Purpose: Upper tract urothelial carcinoma (UTUC) is a rare form of malignancy comprising only 5% of urothelial cancers. The mainstay of treatment is radical nephroureterectomy (RNU) with bladder cuff excision. Neoadjuvant or adjuvant chemotherapy is often used in locally advanced disease. The role of adjuvant radiotherapy (RT), however, remains controversial. To further explore the potential role of adjuvant RT, we performed a systematic review and meta-analysis of the literature from 1990 to present. Methods and Materials: We identified 810 candidate articles from database searches, of which 67 studies underwent full-text review, with final inclusion of 20 eligible studies. Among the included studies, there were no randomized controlled trials and a single prospective trial, with the remainder being retrospective series. We performed quantitative synthesis of the results by calculating the pooled odds ratios (OR) for the primary outcome of locoregional recurrence (LRR) and secondary outcomes of overall survival (OS), cancer-specific survival (CSS) and distant recurrence (DR). Results: Adjuvant RT, which was mostly prescribed for locally advanced or margin-positive disease following RNU, significantly reduced locoregional recurrence risk OR 0.43 (95% CI: 0.23–0.70), and the effect remained significant even following subgroup analysis to account for adjuvant systemic therapy. The effect of adjuvant RT on 3-year OS, 5-year CSS and DR was non-significant. However, 5-year OS was unfavourable in the adjuvant RT arm, but study heterogeneity was high, and analysis of small-study effects and subgroups suggested bias in reporting of outcomes. Conclusions: Adjuvant RT in the setting of locally advanced UTUC improves locoregional control following definitive surgery, but does not appear to improve OS. Higher-quality studies, ideally randomized controlled trials, are needed to further quantify its benefit in this setting, and to explore multi-modal treatments that include systemic agents given concomitantly or sequentially with RT, which may offer an OS benefit in addition to the locoregional control benefit of RT.

Case report: Stereotactic MR-guided adaptive radiotherapy for inoperable urothelial carcinoma at the renal pelvis

“…The current EAU guideline mentioned the role of radiotherapy in UTUC as an adjuvant treatment, which is still controversial ( 2 ). In the latest systematic review and meta-analysis including 20 studies with 6,529 patients, adjuvant radiotherapy usually is given in cases with locally advanced disease, positive lymph nodes, or positive surgical margin, and it could only reduce locoregional recurrence risk with similar survival at 3 years and worsening survival at 5 years ( 10 ). However, the effect of radiotherapy on survival should be cautiously interpreted due to a small arm of adjuvant radiotherapy, selection bias with higher-risk patients assigned to the radiotherapy arm and treatment techniques, especially in older studies that treated with a larger and less conformal field of treatment leading to underdosed target volume and increased toxicity ( 10 ).…”

Establishment and validation of a nomogram for predicting overall survival of upper-tract urothelial carcinoma with bone metastasis: a population-based study

“…Standard treatments for UTUC include radical nephroureterectomy, chemotherapy, and radiotherapy [ 5 , 6 ]. However, there is a lack of research on the management of UTUC patients with BM.…”

Function-preserving high-dose adaptive radiotherapy for renal pelvic cancer in a solitary functioning kidney with severe dysfunction: A case report

“…However, if the only remaining kidney is affected by cancer, surgical resection may cure the cancer, but dialysis or kidney transplantation will be required [2]. In general, radiotherapy for renal pelvic cancer is given at a total dose of 35 to 55 Gy in standard fractionated doses of 1.8 to 2.0 Gy per fraction over 4 to 6 weeks [3]. Here we report a case of successful highdose adaptive radiotherapy with helical tomotherapy for renal pelvic cancer in a solitary functioning kidney with severe renal dysfunction.…”

“…As far as we know, there is no positive result of primary radiotherapy without surgical resection or chemotherapy. Adjuvant radiotherapy alone or as an adjunct to chemotherapy may improve outcomes in high-risk patients, while primary radiotherapy may be an option in inoperable patients [3]. However, the role of definitive radiotherapy has yet to be determined.…”