Survival Benefit of Pancreatic Metastasectomy of Clear Cell Renal Cell Carcinoma

Survival Benefit of Pancreatic Metastasectomy of Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is known to have a unique predilection for metastasizing to the pancreas. In recent years, clinical series from Europe and the United States have demonstrated encouraging survival outcomes following pancreatic metastasectomy. However, data from East Asian populations remain limited, with only a few case reports available. This study aims to present the experience of pancreatic metastasectomy for ccRCC in a Chinese cohort, focusing on peri-operative outcomes and survival benefits.

The study was conducted at Zhongshan Hospital, Fudan University, and approved by the hospital’s Ethical Committee. Informed consent was obtained from all patients prior to surgery. A prospectively maintained surgical database was used to identify ten patients with pancreatic metastasis of ccRCC treated between July 15, 2007, and April 9, 2019. Data collected included patient demographics, primary tumor characteristics, time interval to pancreatic metastasis, surgical details, post-operative complications, and survival outcomes. Overall survival was calculated from the time of pancreatic metastasectomy to cancer-related death or the last follow-up. Statistical analysis was performed using SPSS version 20.0, with survival analysis conducted using life tables and Kaplan-Meier methods.

The primary ccRCC lesions were located in the right kidney in six patients and the left kidney in four patients. The cohort consisted of six males and four females, with a median tumor size of 5.5 cm (range: 2–10 cm). Nine patients were classified as TNM stage II, and one as stage III. Only one patient received interferon therapy following renal surgery. Two patients had recurrent contralateral ccRCC treated with partial nephrectomy prior to pancreatic metastasis. One patient developed a solitary lung metastasis, which was resected before pancreatic metastasectomy.

Pancreatic metastasis of ccRCC accounted for 0.5% of all pancreatic malignancies during the study period. The median age at pancreatic surgery was 58.7 years (range: 51.0–68.0 years). Most patients were asymptomatic, with only two presenting with upper abdominal pain. Imaging revealed hyper-vascular lesions with intense homogeneous contrast enhancement in the arterial phase, which tended to be less detectable in delayed phases.

Clinicopathologic characteristics of the ten patients are detailed in Table 1. The median time interval from initial renal surgery to pancreatic metastasis was 73.4 months (range: 4.4–182.7 months). Pancreatic metastasis was solitary in nine cases and multifocal in one. Lesions were located in the pancreatic head in four cases, body-tail in five, and both head and body-tail in one. The median size of the metastasis was 2.4 cm (range: 0.9–4.9 cm). Surgical procedures included distal pancreatectomy in five cases, pancreaticoduodenectomy in four, and total pancreatectomy in one. Post-operative complications included grade B pancreatic fistula in one patient and grade C in another. There was no peri-operative mortality. Immunohistochemistry confirmed ccRCC through positive staining for carbonic anhydrase 9 (CA-9) and paired box gene 8 (PAX8), while negative staining for synaptophysin, CD56, and chromogranin A ruled out neuroendocrine tumors.

The median follow-up time was 59.6 months (range: 0.7–99.1 months). Liver metastasis developed in one patient 3.5 months post-surgery and was treated with transarterial chemoembolization. Two patients received post-operative chemotherapy, while two others were treated with tyrosine kinase inhibitors (sorafenib and pazopanib). The remaining patients did not receive any post-operative treatment. At the last follow-up, six patients were alive, and four had died. The median overall survival after pancreatic metastasectomy was 77 months, with 1-, 3-, and 5-year survival rates of 100%, 100%, and 60%, respectively.

The study highlights the significant survival benefit of pancreatic metastasectomy for ccRCC, with a median survival of 77 months. This finding aligns with a large-sample Italian multicenter study, which found no significant survival difference between surgical resection and tyrosine kinase inhibitors. However, the decision to perform pancreatic metastasectomy should be carefully evaluated, considering the patient’s specific condition and the potential for preserving pancreatic function.

Peri-operative outcomes in this study were favorable, with no peri-operative mortality and only two cases of post-operative complications. This suggests that pancreatic metastasectomy is feasible and safe, particularly in high-volume pancreatic centers. The choice between typical and atypical pancreatic surgery remains controversial, as some studies suggest that lesion enucleation may better preserve pancreatic exocrine and endocrine function, especially given the relatively indolent nature of metastatic ccRCC.

The study has several limitations. Firstly, the rarity of pancreatic metastasis from ccRCC makes it challenging to conduct prospective clinical trials. Secondly, post-operative regimens following both primary renal surgery and pancreatic metastasectomy were not standardized. Thirdly, the single-center experience and small sample size limit the ability to analyze prognostic risk factors.

In conclusion, pancreatic metastasectomy offers long-term survival benefits for some patients with ccRCC pancreatic metastasis, with acceptable morbidity. However, the decision to proceed with surgery should be individualized, taking into account the patient’s overall condition and the potential for preserving pancreatic function. Further large-sample, multi-institutional studies are needed to confirm these findings and establish standardized guidelines for managing this rare condition.

doi.org/10.1097/CM9.0000000000000500

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