International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationOutcomes in a Multi-institutional Cohort of Patients Treated With Intraoperative Radiation Therapy for Advanced or Recurrent Renal Cell Carcinoma
Introduction
Renal cell carcinoma (RCC) is the predominant histology among renal neoplasms, and roughly one-third of patients presenting with RCC will have locally advanced disease (eg, clinical T3/T4), although the majority of these patients do not have distant metastases evident at that time (1). The standard treatment for T2-4 disease includes nephrectomy with or without adjuvant immunotherapy, targeted therapy, or both (2). Up to 9% of all RCC patients will experience a local tumor recurrence apparently limited to the renal fossa after nephrectomy 3, 4, 5. The treatment options for this cohort include targeted therapies, immunotherapy, and surgical resection with or without intraoperative radiation therapy (IORT). IORT is a treatment modality commonly used in colorectal and breast cancers, although its use has been explored in other disease sites (6). The treatment of RCC with IORT for locally advanced disease at the time of nephrectomy or for locally recurrent disease at time of resection for relapse has been performed since the 1980s and may be combined with preoperative or postoperative external beam radiation therapy (EBRT). IORT is intended to address microscopically or macroscopically persistent disease at the margins when tumor is incompletely resected. When there is extensive local burden at presentation or recurrence and eradication by surgery appears to be unlikely, several institutions now take a planned approach that combines perioperative EBRT with an IORT boost. Similar to treating RCC metastases with radiosurgery, the large single-fraction dose provided by IORT may be particularly useful against a tumor that is commonly thought to be relatively radiation resistant (7). The addition of IORT in primary and recurrent settings has been previously reported in small single-institution cohorts, with encouraging initial results 8, 9, 10, 11, 12. In this study, we sought to examine prognostic factors and disease outcomes in a large pooled multi-institutional cohort of patients who received IORT for RCC.
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Patient and clinical variables
After receiving institutional review board approval, we retrospectively identified 98 patients at 9 institutions who were treated with IORT during surgery for locally advanced or locally recurrent RCC between 1985 and 2010. A wide range of variables was collected from each institution, assessing demographic details, initial clinical and pathologic stages, information on treatment methods for primary and recurrent tumors, duration of in-patient hospital stay, prevalence of perioperative
Patient and tumor characteristics
Patient demographics and disease characteristics are presented in Table 1. Sixty-nine percent of patients were male, and the median age at RCC diagnosis was 58 years. At the time of primary resection, the T stage was 17% T1, 12% T2, 55% T3, and 16% T4.
Treatment characteristics
IORT was delivered during nephrectomy for advanced disease as determined by the treating institution (28% of patients) or during resection of locally recurrent RCC in the renal fossa (72%). Three patients received IORT twice during subsequent
Discussion
In the setting of advanced primary or locally recurrent RCC, IORT has been performed internationally for 3 decades, although rigorous evidence supporting this practice has been lacking. In this multi-institutional pooled analysis, we report on the largest known cohort of RCC patients managed with IORT and have identified several factors associated with survival.
The results from our cohort compare favorably with those of other cohorts treated by local resection alone. The largest contemporary
Conclusions
In summary, we believe that a good candidate for consideration of IORT would include a patient without evidence of distant disease who has a local recurrence of RCC in the renal fossa after nephrectomy for which surgery alone is unlikely to achieve durable local control and for whom external beam dose would be limited by surrounding normal tissues. In light of the encouraging results of our study, namely the potential for improved DFS, we feel that a prospective evaluation of multimodality
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Cited by (22)
Radiation Therapy for Patients with Advanced Renal Cell Carcinoma
2020, Urologic Clinics of North AmericaCitation Excerpt :Intraoperative radiation therapy (IORT) allows precise localization of the tumor bed while minimizing radiation dose to the surrounding normal organs. This approach was studied in multiple retrospective series,33–35 the largest of which was a multicenter cohort of 98 patients, 71% of whom had T3 to T4 disease.35 More than half of these patients received either neoadjuvant or adjuvant external beam RT, and 5-year disease-free survival was favorable compared with surgery alone, although in general isolated local recurrence is a rare event even in patients with LA RCC.31
Treating the Chameleon: Radiotherapy in the management of Renal Cell Cancer
2019, Clinical and Translational Radiation OncologyCitation Excerpt :The use of intraoperative RT (IORT) in patients with RCC, particularly in those with locally recurrent and/or advanced-stage non-metastatic disease, has also been reported. Data from one of the largest series, consisting of 98 patients from nine different institutions, revealed that the 5-year disease-specific and disease-free survival rates compare favourably to those of patients in surgical series without use of IORT [31]. However, given the paucity of data available on the outcomes following this approach, intraoperative irradiation for RCC should still be considered experimental.
Systematic Review of the Management of Local Kidney Cancer Relapse
2018, European Urology OncologyCitation Excerpt :In this series, grade 3–5 toxicities (National Cancer Institute Common Terminology Criteria for Adverse Events) were observed in five patients. The largest published series reported on 98 cases of advanced (n = 27) or recurrent RCC (n = 71) treated with IORT and EBRT [48]. The authors identified factors independently predicting PFS, CSS, and OS.
Current Role of Radiotherapy for Renal-Cell Carcinoma: Review
2017, Clinical Genitourinary CancerCitation Excerpt :Five patients (23%) experienced acute or late grade 3 to 5 toxicities. These results were updated with a larger cohort of RCC patients and published in 201426; the outcomes for patients receiving IORT in the setting of local recurrence compared favorably to similar cohorts treated by local resection alone, suggesting the potential for improved disease-free survival with IORT. An even more exciting mechanism to increase the effectiveness of RT without further dose escalation is through combination of RT with targeted agents.
Kidney and Ureteral Carcinoma
2015, Clinical Radiation Oncology
Conflict of interest: none.