Clinical Investigation
Outcomes in a Multi-institutional Cohort of Patients Treated With Intraoperative Radiation Therapy for Advanced or Recurrent Renal Cell Carcinoma

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Purpose/Objective(s)

This study aimed to analyze outcomes in a multi-institutional cohort of patients with advanced or recurrent renal cell carcinoma (RCC) who were treated with intraoperative radiation therapy (IORT).

Methods and Materials

Between 1985 and 2010, 98 patients received IORT for advanced or locally recurrent RCC at 9 institutions. The median follow-up time for surviving patients was 3.5 years. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were estimated with the Kaplan-Meier method. Chained imputation accounted for missing data, and multivariate Cox hazards regression tested significance.

Results

IORT was delivered during nephrectomy for advanced disease (28%) or during resection of locally recurrent RCC in the renal fossa (72%). Sixty-nine percent of the patients were male, and the median age was 58 years. At the time of primary resection, the T stages were as follows: 17% T1, 12% T2, 55% T3, and 16% T4. Eighty-seven percent of the patients had a visibly complete resection of tumor. Preoperative or postoperative external beam radiation therapy was administered to 27% and 35% of patients, respectively. The 5-year OS was 37% for advanced disease and 55% for locally recurrent disease. The respective 5-year DSS was 41% and 60%. The respective 5-year DFS was 39% and 52%. Initial nodal involvement (hazard ratio [HR] 2.9-3.6, P<.01), presence of sarcomatoid features (HR 3.7-6.9, P<.05), and higher IORT dose (HR 1.3, P<.001) were statistically significantly associated with decreased survival. Adjuvant systemic therapy was associated with decreased DSS (HR 2.4, P=.03). For locally recurrent tumors, positive margin status (HR 2.6, P=.01) was associated with decreased OS.

Conclusions

We report the largest known cohort of patients with RCC managed by IORT and have identified several factors associated with survival. The outcomes for patients receiving IORT in the setting of local recurrence compare favorably to similar cohorts treated by local resection alone suggesting the potential for improved DFS with IORT.

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.

Section snippets

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

References (19)

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Cited by (22)

  • Radiation Therapy for Patients with Advanced Renal Cell Carcinoma

    2020, Urologic Clinics of North America
    Citation 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 Oncology
    Citation 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 Oncology
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    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 Cancer
    Citation 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
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