Surveillance after resection of pancreatic ductal adenocarcinoma: How to do it and what are the benefits?

Abstract

Background and objective:

Surveillance following resection with curative intent of pancreatic cancer varies widely, and supporting evidence is limited. Recurrence is although frequent, not at least during the first 2 years. Surveillance may be costly, but evidence on how this influences overall survival is not fully elucidated.

Methods, Results:

There are reports implying that signs of biological recurrence (increasing CA 19-9) precede radiologically demonstrated recurrence by months.

Conclusions:

The possibility of initiating salvage therapy earlier is discussed, potentially based on improved future biomarker panels.

Pancreatic ductal adenocarcinoma (PDAC) has a desolate prognosis. Most patients present with advanced disease. However, even in the subset of patients with potentially curative disease undergoing resection and receiving adjuvant (and potentially neoadjuvant) chemotherapy, recurrence is common.

The scientific evidence supporting postoperative surveillance after resection for PDAC is quite scant. A number of guidelines, such as the one from the European Society for Medical Oncology (ESMO), do not find evidence for usefulness for regular follow-up after therapy with curative intent. Other guidelines recommend a variety of surveillance protocols varying from clinical evaluations, control of CA 19-9, computed tomography (CT), or a combination of all. The American Society of Clinical Oncology (ASCO) has recommended regular surveillance with 3- to 6-month intervals. Some countries like Sweden recommend clinical follow-up with 3–6 months interval initially and then CT on the suspicion of a recurrence for up to 3–5 years after surgery.

In a recent meta-analysis, ¹ it was found that patients included in a postoperative surveillance program were more likely to have recurrence detected at an asymptomatic stage and more often received rescue therapy, resulting in prolonged survival. Chemotherapy is the most common treatment for recurrence. However, surgical therapy may also be viable option in certain cases. For patients with isolated recurrence in the residual pancreas or in the lung, resection may improve survival. ²

Thus, detecting asymptomatic recurrence seems to be important. However, looking on the mode of surveillance raises the question of what is clinically and cost-effectively beneficial. In the United States, the number of CT scans used for pancreatic cancer surveillance has increased dramatically over the past years without affecting overall survival. ³ Some argue that increasing frequency and intensity of surveillance protocols may result in higher costs without adding survival benefits compared to surveillance by CA 19-9 every 6 months. ⁴

It seems clear that biomarkers have an important role in the detection of asymptomatic recurrence. Often the increase in biomarker levels precedes radiological evidence of recurrence, the interval between the biochemical and radiological recurrence being up to 3–6 months. CA 19-9 has a sensitivity between 68% and 89% and a specificity between 77% and 89% for the detection of postoperative recurrence. ⁵ CEA has a lower diagnostic yield, with a sensitivity of 50% and a specificity of 65%. Additional biomarkers have been evaluated, either alone or in combination with CA 19-9 to improve diagnostic performance. Soluble iC3b levels were found to be increased up to 4 months before radiological evidence of recurrence, with an area under curve (AUC) of 0.85, which could be increased to 0.92 when combined with CA 19-9. ⁶ Multiple liquid biopsy methods—such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes—have been applied at the time of diagnosis in research settings, but their role in postoperative surveillance remains to be seen.

In summary, recent evidence suggests that surveillance programs have some clinical benefit. From the patient’s point of view, they confer comfort and may avoid unnecessary contacts with the primary care, for example, general practitioners. Importantly, detection of asymptomatic recurrence has the potential to improve survival. Overall indications are that surveillance by blood-borne biomarkers may be a good option, lowering costs and detecting potential recurrence prior to radiological verification, increasing the proportion with asymptomatic recurrences, and possibly rendering a higher rate of salvage treatment. Moving beyond CA 19-9, future biomarkers may also aid in selection of patients who might benefit from a specific treatment regimen.