Post-Progression Survival in Patients with Oligometastatic or Polymetastatic Pancreatic Adenocarcinoma

Abstract

Distant progression following surgical resection of stage I-III pancreatic ducal adenocarcinoma (PDAC) is a major cause of morbidity and mortality. Herein, we investigated the impact of tumor burden at the time of distant progression on survival. We hypothesize that patients with limited number of metastases (≤5) in a single organ will have improved survival post progression. We queried our institutional database for patients with the following inclusion criteria: 1-Stage I-III PDAC who underwent curative resection, and 2-Metachronous single organ (liver or lung) distant failure >3 months from the date of surgery. Patients with serosal and/or multiple organ metastases were excluded. Single organ metastases other than liver or lung were also excluded. Patients were stratified into oligometastatic (≤5 tumors), and polymetastatic (>5 tumors). Primary endpoint was survival post failure, while secondary endpoints were distant failure free survival (DFFS) and overall survival. Reverse KM curve was used to calculate median follow up. KM curves were plotted for DFFS identified from date of surgery until date of distant failure, survival post failure was identified from date of distant failure until death/last follow up, and overall survival was identified from date of surgical resection until death/last follow up. Out of 128 patients who developed metachronous distant progression following surgical resection, we identified 76 patients who met the inclusion criteria with a median follow up of 50 months. Among those, at the time of distant failure, 63% (n = 48) and 37% (n = 28) patients had ≤5 vs >5 metastases respectively. Median number of metastases was one (range 1-5) and eight (range 6-33), while 12 and 11 patients developed local failure in the oligometastatic and polymetastatic cohorts respectively. Among the 48 patients who developed oligometastases, 69% (n = 33) and 31% (n = 15) had liver and lung metastases respectively. On the other hand, 68% (n = 19) and 32% (n = 9) had liver and lung polymetastases respectively. Median DFFS was 11, and 9 months (HR = 1.59, 95 % CI 0.95-2.64, p value = 0.046), survival post distant failure was 17.8 and 5.3 months (HR = 3.03, 95 % CI 1.52-6.01, p value<0.0001), and median survival was 29.8, and 16.7 months (HR = 2.52, 95 % CI 1.31-4.86, p value = 0.0007) among patients with oligometastases and polymetastases respectively. Within the surgically resected stage I-III PDAC who developed single organ liver or lung metachronous disease, oligometastases (one-five lesions) were more prevalent, had more durable DFFS, had improved survival post failure, and a longer median survival compared to patients with polymetastatic recurrence (>five metastases). Trials on treatment of metastatic PDAC should stratify by number of metastases, and the oligometastatic subset may derive survival benefit from ablative radiation therapy.