A Plea for Surgery in Pancreatic Metastases from Renal Cell Carcinoma: Indications and Outcome from a Multicenter Surgical Experience

Abstract

Background: Pancreatic metastases from renal-cell carcinoma (RCC-PMs) are rare. Surgery may play a role in improving overall (OS) and disease-free survival (DFS). Methods: Clinical-pathological features, surgery and follow-up data of patients with RCC-PMs operated on in three pancreatic surgical centers (2000–2019) were retrospectively evaluated. Results: Thirty-nine patients (21 male/18 female, averaging 65 years) were enrolled. RCC-PMs were metachronous in 36 patients (mean 94 months, up to 24 years after nephrectomy), multiple in 21 patients, and with a median size of 2.5 (range, 0.7–7.5) cm. All the patients underwent pancreatic surgery (33 standard resections, 6 limited resections). Fifteen patients had post-operative complications (morbidity 38.5%). The median DFS was 63 months, and 19 out of 36 patients showed a disease recurrence. The median OS was 134 months, and 13 out of 36 patients were alive with no evidence of disease. At univariate analysis, lymph node positivity (HR 5.1, 95% CI 1.5–18), multi-visceral resection (HR 3.4, 95% CI 1.1–10) and synchronous RCC-PMs (HR 13, 95% CI 3–55) were significantly associated with a short OS. Conclusion: Surgery may allow a DFS up to 17 years in more than one third of patients, even after limited resections. Splenectomy and lymph node dissection are not mandatory.

Tumour Evolution and Seed and Soil Mechanism in Pancreatic Metastases of Renal Cell Carcinoma

“…IsPMRCC are rare observations in which singular or multiple, synchronous or metachronous to the RCC distant metastases occur definitely or over a longer period exclusively in the pancreas. Since the last literature overview ( n = 1034) covering the years 1952 to 2019 [ 51 ] a further 173 isPMRCC observations could be added [ 27 , 28 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. These 1207 observations serve as a basis for a literature review with meta-analysis.…”

“…An interval of 9.6 (SD 6.8) years was calculated from 470 individually documented observations [ 28 , 51 , 52 , 53 , 55 ]. In single institution reports [ 27 , 30 , 32 , 33 , 34 , 39 , 40 , 41 , 44 , 47 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ], values from 5.3 [ 34 ] to 14 years [ 27 ] are documented ( Table S1 ); the longest interval reported so far is 36 years [ 81 ]; (2) the frequent occurrence of multiple PM: Of 592 documented cases, 39.2% were multiple PM, with a mean of 3.1 pancreatic foci [ 82 ] and a maximum of 15 foci [ 28 ], and in large case compilations [ 27 , 30 , 33 , 34 , 35 ,…”

“…From 445 isPMRCC cases, a cumulative 5-year survival rate of 74.2% was calculated. In single institution reports [ 24 , 27 , 28 , 30 , 31 , 32 , 34 , 35 , 39 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 56 , 57 , 64 , 66 , 67 , 68 , 69 , 71 , 74 , 75 , 76 , 78 , 79 , 83 , 84 , 85 ], values from 43% [ 78 ] to 100% [ 85 ] are presented with a median of 71%, and for the median overall survival following PM treatment, (OS) values from 3.4 [ 74 ] to 8.75 years [ 34 ], with a median of 6.2 years ( Table S3 ) are reported. Further metastases after isPMRCC surgery [ 68 ] were observed in 124 [ 21 , 23 , 28 , 33 , 34 , 39 , 42 , 52 , 53 , 55 , 70 , 71 , …”

“…However, a high importance of these two MPs is countered by the fact that there are no reports of more frequent peripancreatic LN metastases in isPMRCC—that would be expected in lymphogenic tumour cell propagation—nor are there more frequent postoperative liver metastases that would be expected to be associated with a high impact of reno-portal anastomosis in tumour cell spread. For the frequency of peripancreatic LN metastases ( Table S5 ), a value of 6.2% is calculated from 481 observations [ 28 , 30 , 32 , 35 , 41 , 43 , 56 , 57 , 68 , 69 , 71 , 73 , 75 , 76 , 84 , 88 , 122 , 123 ], and for the frequency of later liver metastases ( Table S6 ) a value of 8.7% can be obtained from 288 observations documenting the postoperative outcome [ 21 , 28 , 33 , 34 , 42 , 70 , 80 , 84 , 87 , 89 , 90 , 91 , 92 , 93 , 94 , 124 ]. These results attribute little if any importance to a local MP, whether lymphogenic or venous.…”

“…In a literature compilation in 2006 [ 21 ], our working group demonstrated, however, that the treatment results are not influenced by the singular or multiple or by the synchronous or metachronous occurrence of the PM. The current literature search revealed 12 large ( n > 20) institutional reports and compilations [ 30 , 35 , 38 , 47 , 51 , 56 , 57 , 65 , 68 , 69 , 72 , 111 ] in which data on the impact of clinical risk factors on the OS of operated isPMRCC were presented ( Table 2 ). (The institutional reports were all retrospective and spanned multi-year periods (15–37 years).…”