Detection and Treatment of Pancreatic Cancer Recurrence

The lack of effective treatment options has led to a reluctant attitude towards recurrence-focused surveillance for early detection of pancreatic ductal adenocarcinoma (PDAC) recurrence in most pancreatic cancer clinicians. Given the recent advancements in PDAC treatment, most importantly the development of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) chemotherapy, this point of view may deserve some reconsideration. This thesis elaborates on the debate regarding the value of standardized surveillance after PDAC resection and challenges the persisting nihilism surrounding the detection and treatment of PDAC recurrence.

Opinions on and recommendations for surveillance after PDAC resection widely vary throughout the world. Serial CA 19-9 testing and routine CT imaging at a three-monthly interval during the first two years after surgery is currently considered the optimal surveillance strategy for early detection of PDAC recurrence (chapter 4, 6 and 7). With a pooled sensitivity of 73% and specificity of 83%, the diagnostic accuracy of CA 19-9 for the detection of PDAC recurrence is modest (chapter 2). CT-imaging was only found to have a moderate diagnostic accuracy, reflected by a pooled sensitivity of 70% and specificity of 80% (chapter 3).

With a symptomatic follow-up approach, without routine imaging, PDAC recurrence is generally detected at a more advanced disease stage (chapter 5). Deterioration of the patients’ performance status due to disease progression might hinder these patients to receive additional treatment. In chapter 8 it was shown that treatment for PDAC recurrence is associated with survival benefits, and asymptomatic patients were more likely to receive recurrence treatment than symptomatic patients. In addition, it was found that patients who received follow-up imaging had a better survival, as compared with patients who were subjected to a symptomatic follow-up approach.

Certain patterns of PDAC recurrence have shown a distinct prognosis and may therefore require different treatment strategies (chapter 11). Although survival is predominantly determined by systemic disease control, additional local ablative therapy might be of value to improve local tumor control in patients with local PDAC recurrence. This could provide the best chance for prolonged survival in good quality of life. Online adaptive MR-guided radiotherapy seems to be a promising, minimally-invasive treatment modality for local treatment of patients with upper abdominal malignancies that merits further optimization (chapter 9 and 10).

To increase the chance of optimal delivery of systemic treatment in patients who are eligible for tumor resection, a rising interest in neoadjuvant therapy exists. In particular for selected patients, for instance those who have a high risk of early recurrence (chapter 12) or incomplete tumor resection (chapter 13), initial systemic treatment might be considered. Prognostic studies could aid in preoperative risk stratification of individual patients with resectable PDAC in whom neoadjuvant therapy might be an option.

In conclusion, ongoing developments and insights in PDAC treatment and patterns of recurrence seem to justify standardized postoperative surveillance for selected patients who are likely to benefit from early detection and treatment of PDAC recurrence. However, the true impact on survival and quality of life for individual patients has yet to be established/