Pancreatic Resections after Chemoradiotherapy for Locally Advanced Ductal Adenocarcinoma: Analysis of Perioperative Outcome and Survival

Abstract

Background: The most accepted treatment for locally advanced pancreatic cancer is chemoradiotherapy. However, indications to and results of pancreatic resections after chemoradiation are not yet defined.Methods: From June 1999 to December 2003, 28 patients with locally advanced pancreatic cancer (group 1) were enrolled for institutional trials of gemcitabine-based chemoradiotherapy. Tumors were stratified as unresectable or borderline resectable according to the pattern of vascular involvement at pretreatment computed tomographic scan. Patients with partial response or stable disease and in-range Ca19-9 were surgically explored. Perioperative outcome and survival of group 1 were compared with 44 patients primary resected for localized cancer with or without adjuvant treatment in the same time period (group 2).Results: Only one unresectable tumor was successfully resected compared to 7 out of 18 (39%) that were borderline resectable. Operations after chemoradiation were 1 hour longer and postoperative stays 5 days longer, but transfusion rate, morbidity, and mortality were not significantly different. Median survival was 15.4 months for group 1 (>21 for resected vs. 10 for not resected, P < 0.01) and 14 months for group 2. In both groups, a disease-free survival beyond 24 months was recorded only among patients resected with negative margins.Conclusions: The conversion of an unresectable cancer to a resectable one is a rare event. On the contrary, the resection of a borderline resectable tumor was successfully accomplished in one-third of cases. Chemoradiotherapy did not increase the operative risk, but the interventions were more technically demanding and required a longer postoperative stay. Patients resected after chemoradiation for a locally advanced tumor had at least the same survival as those primary resected for a localized one. Only R0 resections in both groups gave the chance of disease-free survival longer than 24 months.

Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma

“…The most important features of the individual studies that were included in the systematic review and meta‐analysis are summarized in Table 1 6 8, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25. The majority of studies6 8, 16, 17, 18, 19, 20, 21, 22, 23, 24 compared neoadjuvant chemoradiotherapy with primary surgery.…”

“…The majority of studies6 8, 16, 17, 18, 19, 20, 21, 22, 23, 24 compared neoadjuvant chemoradiotherapy with primary surgery. Only a single study25 compared neoadjuvant chemotherapy with primary surgery, and another16 included both neoadjuvant regimens in the analyses.…”

“…In contrast to local recurrence, neoadjuvant therapy did not influence distant recurrence, which developed in 283 (50·2 per cent) of 564 patients in the neoadjuvant group versus 334 (49·6 per cent) of 674 in the surgery‐first group. The estimated RR of the meta‐analysis, which included 11 studies6 8, 16 18, 19, 20, 21, 22, 23, 24, 25, also failed to show any relevant impact of neoadjuvant therapy on the risk of distant metastasis (RR 1·02, 95 per cent c.i. 0·91 to 1·14; P  = 0·78) ( Fig .…”

“…For this purpose, included studies were screened for information on follow‐up; all but two studies17 21 provided sufficient information. Follow‐up included CT of the abdomen every 3–6 months in six studies19 21, 22, 23, 24, 25, and ultrasound examination every 4 months and CT after 12 months or on demand in two studies18 20. Another study6 performed CT at 1, 4, 6, and then every 12 months after surgery.…”

The Role of Neoadjuvant Therapy in Pancreatic Cancer: A Review

“…Neoadjuvant therapy with the intent of sterilizing the margin could be considered in patients with vascular involvement, with particular attention to restaging to tailor surgical recommendations. Several studies suggest that neoadjuvant chemoradiation may enhance margin-negative resectability rates and improve local control [37,[56][57][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77]. Unfortunately, many of the studies are confounded by inclusion of patients with locally advanced unresectable tumors and lack of strict definition of borderline resectable disease.…”