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10.1245/ASO.2003.02.003
Annals of Surgical Oncology 10:922-926 (2003)
© 2003 Society of Surgical Oncology
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ORIGINAL ARTICLES

Pancreatic Resection for Metastatic Renal Cell Carcinoma: Presentation, Treatment, and Outcome

Calvin H. L. Law, MPH, MD, FRCSC, Alice C. Wei, MSc, MD, FRCSC, Sherif S. Hanna, MD, FRCSC, Mohamed Al-Zahrani, MD, FRCSC, Bryce R. Taylor, MD, FRCSC, Paul D. Greig, MD, FRCSC, Bernard Langer, MD, FRCSC and Steven Gallinger, MD, FRCSC

From the Sunnybrook & Women’s College Health Sciences Centre (CHLL, SSH), University of Toronto, Toronto, Ontario, Canada; and University Health Network (ACW, MA-Z, BRT, PDG, BL, SG), University of Toronto, Toronto, Ontario, Canada.

Correspondence: Address correspondence and reprint requests to: Steven Gallinger, MD, Suite 1225, Mount Sinai Hospital, 600 University Ave., Toronto, ON, Canada, M5G 1X5; Fax: 416-586-8392; E-mail: sgallinger{at}mtsinai.on.ca


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The diverse natural history of renal cell carcinoma (RCC) includes metastases to the pancreas, a very unusual site for distant spread of other cancers. Considering the relatively indolent behavior of some cases of metastatic RCC, pancreatic resection is offered to select patients.

Methods: We reviewed the records of patients at three affiliated university hospital centers who had prior nephrectomy for RCC and subsequent pancreatic resection of metastases.

Results: Fourteen patients—9 women and 5 men with a median age of 63.8 years—underwent a total of 15 pancreatic resections for metastatic RCC. Nine (64%) had solitary metastases. The median interval from nephrectomy to diagnosis of pancreatic metastases was 83 months. The median size of metastases was 4.6 cm. There was one perioperative death. Pancreatic recurrence occurred in five patients (36%), and one patient underwent repeat resection. At a median follow-up of 32 months, seven patients (50%) are alive without evidence of disease, and four patients (28%) are alive with recurrent disease.

Conclusions: Resection of pancreatic metastases from RCC is associated with long-term survival and should be considered for patients in whom complete resection is possible.

Key Words: Pancreatic neoplasm • Metastasis • Renal cell carcinoma • Pancreatectomy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The heterogeneous natural history of renal cell carcinoma (RCC) includes metastasis to the pancreas. This represents an unusual site for distant spread of other malignancies, which include breast, colorectal, and lung cancer, as well as melanoma. Metastases to the pancreas in these other malignancies are typically associated with diffuse systemic disease, but this is not always the case with metastatic RCC.

Pancreatic resection of metastatic RCC has been offered to select patients, especially those whose tumors demonstrate a relatively indolent behavior. Improved survival and effective palliation after pancreatic metastasectomy of RCC has been reported by other groups.1–3 However, because of the rarity of this event, the literature consists mainly of case reports and small case series.1,4–10 The purpose of this study was to review our broader, long-term experience with patients who underwent a pancreatic resection for metastatic RCC.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
The study population consisted of patients who underwent pancreatic resection for RCC metastases between 1991 and 2000 at three University of Toronto–affiliated hospitals. At one site, all pancreatic resections and outcomes had been recorded in a prospective database. In the other two hospitals, patients were identified retrospectively with International Classification of Diseases, revision 9, codes on computerized discharge abstracts. These searches were cross-referenced with individual surgeons’ office records.

Baseline clinical and pathologic data were collected. Outcome data were obtained through computerized chart review and from outpatient records. Survival outcomes were analyzed by the methods of Kaplan and Meier.11 All statistical analyses were performed with SPSS version 10.0 (SPSS Inc., Chicago, IL).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
A total of 14 patients were identified by the search strategy described previously. Mature outcome data were available for all patients. Relevant demographic, tumor, and outcome data are listed in Table 1.


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  		TABLE 1. Patient characteristics
 
There were nine (64%) women and five (36%) men, with a median age of 63.8 years (range, 44.0–74.5 years), at the time of pancreatic resection. Five (35%) of 14 patients were symptomatic. Two patients presented with abdominal pain, and three presented with upper gastrointestinal bleeding. All three patients who presented with upper gastrointestinal bleeding had an intraluminal duodenal mass identified at endoscopy.

The primary RCC originated from the left kidney in nine patients (64%) and from the right in five (36%). The median disease-free interval from primary RCC to pancreatic metastases was 83 months (range, 0–301 months); all but three patients had a disease-free interval of >12 months. Five patients had a preoperative biopsy of the pancreatic metastases before referral. Three patients had nonpancreatic metastases that were resected before their pancreatic surgery. The sites included the brain, lung, and adrenal glands. One patient had a concomitant liver resection with the pancreatic surgery.

Surgical procedures were performed at a median of 5.3 months (range, 0–42.6 months) from the time of diagnosis of the pancreatic metastases. Surgical procedures included pancreaticoduodenectomy (Whipple procedure) in seven patients (50%), distal pancreatectomy in five patients (36%), and total pancreatectomy in two patients (14%). There was one perioperative death in a higher-risk patient (case 2) with a large metastasis in the head of the pancreas, which was bleeding into the duodenum because of direct extension. This subject had undergone bilateral adrenalectomy in the past for treatment of the primary RCC and subsequent metastasis. The Whipple operation was complicated by intraoperative bleeding from an iatrogenic liver injury that occurred during exposure of the head of the pancreas. His postoperative course was complicated by sepsis (which required further surgery) and subsequent multiorgan failure. Complications in the remaining 13 patients included wound infection (n = 2), delayed gastric emptying (n = 2), sepsis (n = 2), new-onset diabetes (n = 1), and bowel obstruction (n = 1).

Solitary metastases were identified in nine patients, six of whom were isolated to the pancreatic head. In the remainder, multiple lesions were identified throughout the pancreatic parenchyma. The median size of metastases was 4.6 cm (range, 2–11.5 cm). One patient had involvement of a regional lymph node (7%). Thirteen (93%) patients had histologically negative resection margins.

The median follow-up from pancreatic resection was 32.1 months (range, .6–134 months). During this time, five patients developed recurrent RCC in the pancreas. One patient (case 8; Table 1) with recurrent pancreatic disease underwent a distal pancreatectomy. Two patients (cases 3 and 11; Table 1) underwent lung metastasectomies for recurrent metastatic RCC after pancreatectomy. In one of these patients, the metastatic lung lesions occurred 10 years after the Whipple procedure. As of September 2002, 7 (50%) of 14 patients are alive with no evidence of recurrence, 4 (29%) patients are alive with disease, and 3 (21%) patients had died. One patient died in the perioperative period because of sepsis and multiorgan failure, and two patients died of recurrent metastatic RCC. With Kaplan-Meier analysis, the 5-year survival after pancreatic metastasectomy for RCC was 75% (Fig. 1).



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  		FIG. 1. Kaplan-Meier analysis: overall survival after pancreatic resection for metastatic renal cell carcinoma.

 
The median follow-up after the original resection for RCC was 129 months (range, 31–315 months). Kaplan-Meier analysis demonstrated a 10-, 15-, and 25-year survival of 75% in this highly selected group of patients with metastatic RCC (Fig. 2). There was no statistical difference in outcome among those patients who had symptomatic or asymptomatic presentations, those who underwent a preoperative biopsy, or those operated on within 6 months of diagnosis and those operated on after 6 months.



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  		FIG. 2. Kaplan-Meier analysis: overall survival after resection of primary renal cell carcinoma.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Although isolated pancreatic metastases from RCC are rare, their behavior is often unusual because some patients have an indolent natural history, with presentation of metastatic RCC many years after treatment of the primary tumor. In this series, 4 (28%) of 14 patients presented with symptoms of metastatic RCC >10 years after nephrectomy. The median time from presentation of the RCC primary tumor to identification of pancreatic metastases was almost 7 years. It should be noted that most patients were asymptomatic, and pancreatic metastases were detected through routine post-RCC surveillance imaging; this demonstrates the importance of long-term follow-up of RCC.

In this series, preoperative assessment included preoperative imaging in all patients and percutaneous biopsy in five patients (36%). Classic features of RCC metastases include lesions with high attenuation on arterial phase computed tomographic scanning consistent with hypervascular tumors (Fig. 3).8,12–19 Primary exocrine tumors of the pancreas usually appear as hypovascular masses. Neuroendocrine tumors of the pancreas are frequently hypervascular. In this series, biopsy had no obvious adverse affect on survival or recurrence. However, given the accuracy of current imaging modalities, we believe that hypervascular pancreatic lesions may be assumed to represent metastases in the appropriate clinical context (i.e., a history of RCC). Therefore, preoperative biopsy is unnecessary and potentially hazardous.



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  		FIG. 3. Radiological features of renal cell carcinoma metastasis to the pancreas. Abdominal computed tomography demonstrates a well-demarcated tumor in the neck of the pancreas (white arrow). Note the hyperattenuation compared with surrounding normal pancreatic parenchyma on arterial phase because of the vascular nature of the tumor.

 
Determining a definite survival benefit from surgical resection for asymptomatic patients with RCC metastases to the pancreas is somewhat difficult. It is easier to conclude that the quality and length of life of symptomatic patients are improved after resection of pancreatic metastases, particularly those who present with gastrointestinal bleeding secondary to erosion of metastases in the head of the pancreas into the duodenum. However, there is likely to be an important psychological benefit for some otherwise asymptomatic patients who often have difficulty coping with the prospect of no treatment for their metastatic disease.

Total pancreatectomy was performed infrequently in our series (two patients) and only when it was absolutely necessary, to encompass all gross metastatic disease in the pancreas (both patients had four discrete metastases scattered throughout the pancreas; Table 1). The long-term morbidity of total pancreatectomy is obviously of concern in these types of cases, although both cases in our series have adapted well to their diabetic state. Formal elective preoperative diabetic education seemed to be helpful in this setting.

In our series, the estimated 5-year survival was 75% after pancreatic resection for RCC metastases. These results are in keeping with other recent series, which have estimated survival rates of 68% to 75% at 5 years.1,6,18 These results are certainly superior to those of patients with widely metastatic, unresected RCC. These latter patients have a poor prognosis, with 1-year survival rates of <50% and 5-year survival rates in the range of 5% to 30%.20,21 Thus, surgical resection of RCC metastases to the pancreas should be considered in all patients in whom complete resection of disease is possible.

In this series, four patients presented with extrapancreatic disease. Despite this seemingly poor prognostic factor, these patients still had long-term survival after resection. In addition, another patient in this series had a lung recurrence resected 10 years after the pancreatic metastasectomy, and this subject currently remains free of disease.

It is likely that the interval from the presentation of the RCC primary tumor to the development of pancreatic metastasis is an important prognostic factor. In this series, two of the three patients who developed pancreatic metastasis within 1 year of their original RCC diagnosis had disease progression with additional metastatic disease, resulting in death due to disease in one patient. Although we did not demonstrate a statistically significant difference between the outcomes of patients with either a short or long interval from the presentation of the RCC to pancreatic metastases, this is most likely due to the small number of patients in the series (median survival after RCC resection: short interval [<12 months] from presentation of RCC to metastases, 78 months; long interval [>12 months], 162 months). In a study by Kavolius et al.,22 which described 278 patients undergoing metastasectomy for RCC to different sites, a disease-free interval of >12 months was a positive predictor of survival at 5 years.

This study also highlights the importance of long-term follow-up for patients with RCC, because metastatic disease may be detected decades after the initial diagnosis. Because the natural history of metastatic RCC to the pancreas is unknown, several of our patients were observed for a period of time before they underwent pancreatic resection (median time, 5.3 months; range, 0–42 months). This observational approach, with a period of "watchful waiting" to monitor the natural history of the patient’s disease, did not affect survival or recurrence in this series and seems most reasonable in select patients who have an increased risk from pancreatic resection.

Of further interest in our study was the identification of RCC metastases in a regional peripancreatic lymph node in one patient. Faure et al.5 commented that no case series had found lymph node positivity and, therefore, that radical resections were not required. We believe that a standard oncological pancreatic resection, which routinely includes regional nodes, is still necessary for RCC pancreatic metastases.

In summary, aggressive surgical metastasectomy of pancreatic metastases from RCC can result in long-term survival. Our series demonstrated a favorable 5-year survival of 75% after pancreatic resection for metastatic RCC. This survival figure is much greater than that seen for resection of primary pancreatic adenocarcinoma, which has a 5-year survival of <25%.23 With the improved safety profile of pancreatic resection in experienced centers, an aggressive surgical approach should be considered in all patients with isolated RCC metastases to the pancreas.


   FOOTNOTES
 
Pancreatic resection for metastatic renal cell carcinoma (RCC) offers long-term survival in select patients. In this study, 14 patients underwent pancreatic metastasectomy for RCC. With a median follow-up of 32 months, a 5-year survival of 75% was found after complete resection of metastatic disease.

Received for publication February 5, 2003. Accepted for publication May 30, 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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  6. Hiotis SP, Klimstra DS, Conlon KC, Brennan MF. Results after pancreatic resection for metastatic lesions. Ann Surg Oncol 2002; 9: 675–9.[Abstract/Free Full Text]
  7. Fabre JM, Rouanet P, Dagues F, Blanc F, Baumel H, Domergue J. Various features and surgical approach of solitary pancreatic metastasis from renal cell carcinoma. Eur J Surg Oncol 1995; 21: 683–6.[CrossRef][Medline]
  8. Ghavamian R, Klein KA, Stephens DH, et al. Renal cell carcinoma metastatic to the pancreas: clinical and radiological features. Mayo Clin Proc 2000; 75: 581–5.[Medline]
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  17. Kanai T, Aoki A, Okazeri S, et al. Successful aggressive treatment against multiple intra-abdominal metastases from renal cell carcinoma 18 years after nephrectomy. Jpn J Clin Oncol 1992; 22: 216–20.[Abstract/Free Full Text]
  18. Kassabian A, Stein J, Jabbour N, et al. Renal cell carcinoma metastatic to the pancreas: a single-institution series and review of the literature. Urology 2000; 56: 211–5.[CrossRef][Medline]
  19. Ng CS, Loyer EM, Iyer RB, David CL, DuBrow RA, Charnsangavej C. Metastases to the pancreas from renal cell carcinoma: findings on three-phase contrast-enhanced helical CT. AJR Am J Roentgenol 1999; 172: 1555–9.[Abstract/Free Full Text]
  20. Walsh PC, Retik AC, Darracott Vaughan E Jr, Wein AJ. Campbell’s Urology. 8th ed. St. Louis: Saunders, 2002.
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