Pancreatic cancer (PCA) is one of the most challenging malignancies faced by patients, their families, and their physicians. Symptoms related to metastatic disease (eg, malaise, fatigue, cachexia, and venous thromboembolism) may all contribute to poor quality of life. Moreover, the local component of PCA may also be associated with significant morbidity, including pain, biliary obstruction, gastrointestinal dysfunction or bleeding, and exocrine or endocrine pancreatic insufficiency. Fortunately, multidisciplinary engagement and multiple therapeutic modalities have gradually improved and been refined to optimize survival while preserving quality of life.
Currently, a convergence of several improved techniques and technologies, coupled with a better understanding of underlying tumor biology, now enables physicians to consider more aggressive therapies for select patients who present with limited metastatic disease.
First, improvements in cross-sectional imaging have facilitated the detection of very low-volume metastatic disease. Such metastatic foci, which can be limited to 1 or 2 lesions in a single organ, may have gone undetected in previous years. In addition, laparoscopy seems to be particularly effective in identifying occult metastatic disease that may otherwise be undetected by modern imaging modalities.1,2
Second, a broader array of radiation options that include image-guided (IGRT) and stereotactic body radiation therapy (SBRT) have demonstrated encouraging efficacy in the treatment of primary and metastatic tumors while minimizing toxicity. Importantly, these techniques can be delivered over relatively short time courses, thus limiting the delay of systemic therapies. However, longer follow-up is needed to determine the full extent of late toxicity.
Third, recent advances in combination chemotherapy yield higher response rates and survival. Although uncommon, some isolated case reports of complete or near-complete radiographic responses have been observed after combination chemotherapy regimens. With the widespread adoption of novel combination chemotherapy regimens, larger subsets of patients with metastatic disease may be considered for novel clinical trials to manage the metastatic compartment as a way to preserve or improve quality of life.
Fourth, image-guided percutaneous radiofrequency ablation (RFA) and laparoscopically assisted RFA may allow for management of limited metastatic disease and spare patients the toxicity associated with ongoing cytotoxic chemotherapy.
Lastly, the morbidity and mortality associated with metastatectomies or primary PCA resections continues to decline, particularly in high-volume centers. Whether these interventions lead to improved overall survival (OS) or disease-free survival (DFS) in the setting of limited metastases is not yet known.
The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
The authors would like to thank Lauren M. Rosati, BS, for her technical assistance and contribution to the revision of this manuscript.
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