Optimal management of recurrent and metastatic upper tract urothelial carcinoma: Implications of intensity modulated radiation therapy

Abstract

Background Upper tract urothelial carcinoma (UTUC) is rare and the treatment for recurrent or metastatic UTUC is unclear. We evaluated the outcomes of salvage and palliative radiotherapy (RT) and prognostic factors in UTUC patients and find implications for salvage and palliative RT. Methods Between August 2006 and February 2021, 174 patients (median age, 68 years; range, 37–90) underwent salvage and palliative RT. Disease status at RT included initially diagnosed advanced disease (n = 8, 4.6%), local recurrence only (n = 56, 32.2%), distant metastasis only (n = 59, 33.9%), and local recurrence and distant metastasis (n = 51, 29.3%). The primary tumor location included the renal pelvis (n = 87, 50%), ureter (n = 77, 44.3%), and both (n = 10, 5.7%). Radical nephroureterectomy, chemotherapy, and immunotherapy were used in 135 (77.6%), 101 (58%), and 19 (10.9%) patients, respectively. Survival outcomes and prognostic factors were analysed using Cox and logistic regression analysis. Results Salvage RT and palliative RT was administered in 73 (42%) and 101 (58%) patients, respectively. The median radiation dose was 45 Gy (range, 15–65). Two-dimensional (2D) or three-dimensional (3D) RT and intensity modulated RT (IMRT) were used in 61 (35.1%) and 113 (64.9%) patients, respectively. The median follow-up was 7.8 months. The median duration of overall survival (OS) was 13.4 months, and the 1-year OS was 53.5%. The median progression-free survival (PFS) was 4.7 months, and the 6-month PFS was 41.9%. The 6-month infield PFS was 84%. In multivariate analysis, RT method (2D/3D vs. IMRT, p = 0.007) and RT response (p = 0.008) were independent prognostic factors for OS, and RT response correlated with PFS (p = 0.015). In subgroup analysis in patients with PD-L1 data, positive PD-L1 correlated with better PFS (p = 0.009). RT response-associated factors were concurrent chemotherapy (p = 0.03) and higher radiation dose (p = 0.034). Of 145 patients, 10 (6.9%) developed grade 3 acute or late toxicity. Conclusions Salvage and palliative RT for UTUC are feasible and effective. Patients with RT response using IMRT may have survival benefit from salvage and palliative RT. Positive PD-L1 status might be related to radiosensitivity. High-dose radiation with concurrent chemotherapy may improve RT response.

Upper Tract Urinary Carcinoma: A Unique Immuno-Molecular Entity and a Clinical Challenge in the Current Therapeutic Scenario

“…The role of radiotherapy (RT) for UTUC management has not been clearly elucidated, since evidence on salvage/palliative RT in patients with recurrent UTUC is still scarce. 73…”

“…The role of radiotherapy (RT) for UTUC management has not been clearly elucidated, since evidence on salvage/palliative RT in patients with recurrent UTUC is still scarce. 73 RT may offer a safe therapeutic alternative in such patients with nonmetastatic UTUC who cannot tolerate or refuse surgery. 74 Therapeutic Approaches: Advanced Disease Role of CT in Metastatic Disease.…”

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

“…In contrast to the EAU guideline, the AUA guideline recommended radiotherapy only as one of the palliative treatment modalities for symptomatic relief in inoperable UTUC patients ( 5 ). A large retrospective study of salvage or palliative radiotherapy in recurrent or metastatic UTUC showed that the treatment is feasible and effective especially with intensity-modulated radiotherapy (IMRT) to escalate higher dose or concurrent chemotherapy to improve the radiotherapy response ( 11 ). In a small case series, five-fraction stereotactic body radiotherapy with dose varied from 35 to 45 Gy is an effective treatment for palliation of gross hematuria from UTUC at the renal pelvis in patients who were unfavorable surgical candidates but have a moderate decline of renal function without patients who required hemodialysis ( 12 ).…”

Robotic nephroureterectomy supplanting open and laparoscopic approach for upper tract urothelial carcinoma management: a narrative review

“…Leaving the bladder cuff intact at the time of radical surgery is associated with a known recurrence rate 33–75% in the ureteric remnant ( 62 , 63 ). In 2015, the first series of cases involving pure RAL-NU and BCE was described, demonstrating satisfactory oncologic control at 12months of follow-up ( 64 ).…”