Editor's Note: Urothelial carcinoma (UC) is one of the most common malignant tumors of the urinary system, encompassing bladder cancer, renal pelvic cancer, and ureteral cancer. Radiotherapy, as a critical treatment modality for tumors, has gained prominence in the comprehensive treatment of UC, offering hope for improved survival outcomes. During the 8th West China Urologic Oncology Academic Conference held in Chengdu, Oncology Frontier invited Dr. Hongzhen Li from Peking University First Hospital to share the latest advancements in radiotherapy for UC.Radiotherapy in Urothelial Tumors
Urothelial tumors are the most common malignancies of the urinary system, including bladder cancer, renal pelvic cancer, and ureteral cancer. For bladder cancer, radiotherapy plays a pivotal role in managing muscle-invasive bladder cancer (MIBC), bladder cancer with regional lymph node metastasis (N+BC), adjuvant therapy post-radical surgery, and oligometastatic bladder cancer (OligMBC). In particular, radiotherapy is indispensable in bladder-sparing comprehensive treatment.
For renal pelvic and ureteral cancers, which are categorized as upper tract urothelial carcinoma (UTUC), radiotherapy can be utilized for adjuvant therapy post-surgery, managing metastatic lesions, and as a substitute for radical treatment in patients unfit for surgery.
Applications of Radiotherapy in Bladder Cancer
Muscle-Invasive Bladder Cancer (MIBC)
Due to pre-existing conditions or the potential decline in quality of life after surgery, many patients are unsuitable or unwilling to undergo radical cystectomy (RC). Thus, identifying curative treatments that preserve the bladder is paramount. The classical bladder-sparing treatment model is trimodal therapy (TMT), combining transurethral resection of bladder tumor (TURBT), radiotherapy (RT), and chemotherapy (CT). Multiple prospective studies, including those by RTOG, have demonstrated that TMT is safe, effective, and well-tolerated.
In comparison to radiotherapy alone, concurrent chemoradiotherapy (CRT) significantly improves local tumor control and bladder cancer-specific survival. The British BC2001 trial, a multicenter phase III randomized controlled study, confirmed that CRT enhances local control rates (HR 0.61, P=0.004) and reduces bladder removal rates (14% in the CRT group vs. 22% in the RT group, P=0.034).
Additionally, a retrospective study compared the outcomes of MIBC patients undergoing RC and TMT. After matching cohorts, the study included 837 RC patients and 282 TMT patients, with median follow-ups of 4.4 and 4.9 years, respectively. Results indicated similar efficacy between RC and TMT. Notably, the NCCN guidelines state that surgery is not the sole standard treatment for MIBC, with TMT also recommended as a curative option.
Bladder Cancer with Regional Lymph Node Metastasis
A British multicenter study retrospectively analyzed survival data for 287 patients with pelvic lymph node metastasis (cN1M0) bladder cancer. Five groups received various radical treatments, including chemotherapy combined with RC, standalone RC, chemotherapy combined with radical radiotherapy, standalone radiotherapy, and RC plus adjuvant radiotherapy. Results showed that radical radiotherapy achieved survival outcomes comparable to surgery. Thus, TMT represents a viable option for cN1M0 BC patients, with the NCCN guidelines recommending radical radiotherapy for such cases.
Postoperative Radiotherapy
Postoperative radiotherapy for bladder cancer primarily targets patients with deeply invasive tumors, pelvic lymph node metastases, and positive surgical margins (pT3-4, N0-2, SM+). The treatment scope includes the surgical bed and pelvic lymphatic drainage areas.
Bladder-Sparing Radiotherapy: Peking University First Hospital’s Approach
The standard bladder-sparing treatment model involves TMT (TURBT+RT+CT). Previous studies have shown that the 5-year local recurrence rate within the bladder can reach 39%, with the primary recurrence site being the original tumor. This indicates potential inadequacies in localized radiotherapy dosing, attributed to inaccurate tumor localization and inconsistent bladder filling.
To address these issues, the team employed lipiodol markers and artificial bladder filling methods, leveraging SABR technology to enhance local tumor control rates. Initial results showed a 3-year local control rate of 95%, improving tumor control and enabling more patients to retain their bladder. This research was recognized at the 2023 ASTRO annual meeting, receiving international acclaim.
Radiotherapy for Renal Pelvic and Ureteral Cancer
Postoperative Adjuvant Radiotherapy for UTUC
Globally, UTUC accounts for 5%-10% of urothelial carcinomas, whereas it comprises 20%-25% in China, with patients presenting more advanced stages and higher malignancy. For locally advanced UTUC, postoperative 5-year local recurrence rates can reach 20%-41%. While traditional chemotherapy has not proven effective in reducing local recurrence, studies on IMRT-based adjuvant radiotherapy have shown good tolerability and high local control rates. Consequently, the 2022 NCCN guidelines recommend adjuvant radiotherapy for pT3-4 N+ and margin-positive patients.
Target areas for radiotherapy traditionally include the renal bed, ureteral trajectory, and parts of the bladder. However, research has revealed differences in lymphatic drainage for UTUC. For instance, renal pelvic and upper-mid ureteral cancers rarely metastasize to pelvic lymph nodes, whereas lower ureteral cancers carry risks of pelvic and retroperitoneal lymph node metastases. Additionally, right-sided UTUC poses higher risks for contralateral lymph node metastasis, allowing for tailored radiotherapy target optimization.
Radical Radiotherapy for UTUC
For patients unable to undergo surgery or tolerate platinum-based chemotherapy, standalone radiotherapy or radiotherapy combined with ADCs, immunotherapy, or chemotherapy can achieve curative outcomes in specific cases. In such scenarios, radiotherapy typically targets primary lesions without prophylactic irradiation. Standard or moderately fractionated regimens, including SBRT, may be employed. However, radical radiotherapy for UTUC should be conducted within clinical trials or under informed consent for selected populations.
Radiotherapy for Metastatic UTUC
For patients with synchronous oligometastatic disease, clinical studies have explored comprehensive radiotherapy for both primary and metastatic lesions alongside systemic therapies. Similarly, for metachronous oligoprogressive cases, radiotherapy targeting resistant lesions has been evaluated.
Conclusion
Radiotherapy has become an integral component of comprehensive treatment strategies for urothelial carcinoma, contributing significantly to patient outcomes. Innovations in radiotherapy techniques, such as adaptive radiotherapy and combinations with systemic therapies, continue to push the boundaries of cancer management. Moving forward, further clinical trials and interdisciplinary collaborations will be crucial in optimizing treatment protocols and improving survival outcomes for UC patients.
Dr. Hongzhen Li Director of Medical Affairs, Peking University First Hospital Deputy Head, Radiation Oncology Department
Professional Affiliations:
- Deputy Director, Radiation Oncology Section, Peking University Health Science Center
- Member, Youth Committee, Chinese Medical Association Radiation Oncology Society
- Member, Urological Tumors Group, Chinese Medical Association Radiation Oncology Society
- Deputy Chair, Youth Committee, Beijing Medical Association Radiation Oncology Section
- Member, Beijing Medical Association Radiation Oncology Section
- Deputy Chair, Radiation Therapy Expert Committee, Beijing Cancer Prevention and Treatment Research Society
- Expert Reviewer, Medical Practice Access and Medical Damage Assessment Panels, Beijing Medical Association
Areas of Expertise:
- Radiotherapy for genitourinary tumors: prostate, bladder, kidney, ureter
- Comprehensive treatment strategies for gastrointestinal system cancers: liver, gallbladder, pancreas, stomach
