Metastatic Renal Cell Carcinoma to the Pancreas

As discussed in the case report by Thadani and colleagues, isolated solid organ metastasis to the pancreas occurs infrequently in the absence of widely disseminated dis-ease.^1,2 Of the primary tumors that can metastasize to the pancreas, renal cell carcinoma (RCC) is the most common, followed by lung cancer, breast cancer, colon cancer, and melanoma.^3,4 The incidence of primary RCC in the United States is approximately 50,000 new cases per year, accounting for 3% of all newly diagnosed malignancies.⁵ Patients with RCC or other metastases to the pancreas are typically identified in 1 of 3 ways: The lesion is found during the initial staging work-up for treatment of the primary tumor; the lesion is discovered via routine follow-up imaging after the primary tumor has been treated; or the patient initially presents with symptoms related to the pancreatic lesion, which, on work-up, leads to the identification of the primary tumor. Minni and associates reported that 22% of patients with metastatic lesions to the pancreas were identified at the time of their primary tumor diagnosis.³

In many cases, it can be difficult to distinguish a pancreatic RCC metastasis from a primary pancreatic ductal adenocarcinoma (PDA) or a neuroendocrine tumor (NET) of the pancreas. Patients may be completely asymptomatic, or they may develop symptoms of epigastric abdominal pain or acute pancreatitis secondary to pancreatic ductal obstruction from the metastatic lesion. Other potential signs and symptoms—such as early satiety, gastrointestinal bleeding, or painless jaundice secondary to biliary obstruction—can all be caused by either primary pancreatic neoplasia or isolated metastatic disease to the pancreas. Hiotis and colleagues found that 69% of patients with isolated pancreatic metastasis were completely asymptomatic at presentation.⁶ For patients with primary RCC, the classic symptom triad of flank pain, gross hematuria, and a palpable mass are concurrently present in only 10% of all newly diagnosed cases. Other common symptoms include anemia, microscopic hematuria, and new-onset varicocele.⁷ With the increased use of cross-sectional imaging technology in medicine today, a large number of primary RCCs and even their pancreatic metastases are being identified incidentally.

Cross-sectional radiographic imaging in these patients typically consists of abdominal magnetic resonance imaging/magnetic resonance cholangiopancreatogram or contrast-enhanced abdominal computed tomography with thin cuts through the pancreas. Via these imaging techniques, RCC metastatic disease to the pancreas can often be distinguished from PDA, as the former lesion is hypervascular (leading to contrast enhancement) while the latter lesion typically appears hypointense in the contrast phase. Metastases to the pancreas can be multicentric and typically do not cause peripancreatic lymphadenopa-thy; both of these findings can be used to distinguish metastases from PDA. Of note, pancreatic NETs are also hypervascular and contrast-avid on cross-sectional imaging, such that distinguishing them from RCC metastases to the pancreas can be difficult.

Surgical resection of metastatic disease to the pancreas is appropriate in certain clinical scenarios, depending on the virulence of the primary tumor, the extent of metastatic disease, and the functional status of the patient. The specific type of surgical resection will depend on the location of the tumor within the pancreas. These procedures range from pancreaticoduodenectomy (for tumors in the head, neck, and uncinate process of the pancreas) to middle-segment or distal pancreatectomy (for tumors in the body and tail of the pancreas). In some instances, small isolated metastatic tumors to the pancreas can be treated with enucleation of the lesion, thereby preserving the pancreatic parenchyma. In cases of multicentric pancreatic metastases, total pan-createctomy has been performed, although this treatment approach is fairly uncommon.

Surgery is the principal treatment modality for primary RCC, and complete surgical resection via either partial or complete nephrectomy offers the possibility of cure. Unfortunately, 25% of patients with RCC have locally advanced or widely metastatic disease at the time of diagnosis, precluding surgical intervention.^8,9 The most common sites of RCC metastases are (in descending order) the lungs, lymph nodes, bone, liver, brain, ipsilateral adrenal gland, contra-lateral kidney, and pancreas.¹⁰ In patients with RCC that is amenable to surgical treatment, the traditional therapeutic approach has been radical nephrectomy, including resection of Gerota fascia and the accompanying adrenal gland. This radical procedure is still performed for large tumors, but in most other settings, it has been replaced by less invasive adrenal-sparing and partial nephrectomy procedures, which are often performed using a laparoscopic approach. Adjuvant therapy (chemotherapy, immunotherapy, and/or radiation therapy) following surgical resection has shown disappointing results to date. Recently, there has been promising investigational research into molecular targeted therapy for RCC, specifically involving inhibition of the mammalian target of rapamycin pathway.¹¹

Although metastasis to the pancreas is most commonly associated with disseminated systemic disease, RCC typically spreads to the pancreas as an isolated lesion, often making it amenable to surgical treatment.¹² Most cases of RCC metastasis to the pancreas present as metachronous lesions, often many years after resection of the primary tumor. The average time to presentation for pancreatic metastasis from RCC is 9.2 years after the initial resection.¹³ Autopsy data have shown that 2% of patients with RCC have pancreatic metastases at the time of their death.¹⁴ This finding highlights the importance of long-term postnephrectomy surveillance in patients with RCC. When pancreatic spread of RCC is identified as a synchronous lesion, resection of the metastasis at the time of nephrectomy offers a survival benefit over nephrectomy alone.^15,16 The goals of pancreatic metastasectomy include resection of the lesion with clear surgical margins and preservation of as much viable pancreatic tissue as possible. Five-year survival rates after surgical resection of RCC metastasis to the pancreas are 53—75%, whereas patients who choose not to undergo surgical resection or who have widely disseminated disease have a 5-year survival rate of 5—30%.^13,16,17

Conclusion

When metastasis to the pancreas occurs, it is most commonly associated with widespread disease dissemination. RCC is the most common primary tumor to present with isolated solid metastasis to the pancreas. In a select group of patients with RCC metastasis to the pancreas, surgical metastasectomy can be performed safely and can improve long-term survival.