Why surgeons care about systemic chemotherapy for pancreatic cancer?

| https://dx.doi. org/10.21037/hbsn-21-398 Pancreatic adenocarcinoma (PDAC) has become the seventh most frequent cause of cancer death in the world with increasing incidence independent of patient sex and age with smoking and alcohol consumption being the most important risk factors (1). The high mortality rate is mainly attributed to the biological characteristics of this disease: even small tumors reveal perineural invasion or local spread into lymph and blood vessels resulting in systemic disease. The estimated risk of occult distant metastasis at the time of surgery is 28% and 94% for tumors with a diameter of 1 and 3 cm, respectively (2). Consequently, many patients present with disseminated or locally advanced disease and are at high risk for early tumor recurrence (3). Due to the limited effect of chemotherapy, upfront surgery often included venous resections for presumed or proven vascular infiltration in the past, while arterial resections had been excluded for a long time due to its morbidity. Local treatment options such as surgery, tumor ablation and radiation therapy had been limited to a positively selected minority of patients with technically resectable, non-metastatic disease, in whom surgery was considered “potentially curative”. During the past two decades, adjuvant chemotherapy has proven to improve outcome after PDAC resection. Mavros et al. summarize the available evidence for chemotherapy in resectable PDAC (4). They confirm that adjuvant chemotherapy is the current standard of care, since FOLFIRINOX, nab-paclitaxel/gemcitabine and gemcitabine/capecitabine have proven superiority over gemcitabine-mono therapy. Also, the rationale of neoadjuvant therapy in upfront resectable PDAC is underlined in the manuscript: >50% of patients do not get fit for adjuvant therapy in a reasonable time after surgery, and therefore neoadjuvant therapy may be beneficial (5). The probability of an incomplete resection (R1/R2) as well as the recurrence rate can be predicted by imaging criteria, which classify tumors into locally unresectable (advanced), borderline resectable and upfront resectable tumors (Figure 1). A recent analysis of 268 patients demonstrated that the R0-resection rates in upfront resectable, borderline or unresectable disease were 81.6%, 74.4% and 31.7%, respectively, and the 5-year survival rates were 32.2%, 19% and 0% (6). Also, the depth of invasion of the portal vein is predictive of the recurrence risk (7). These data confirm that upfront surgery should be avoided in borderline resectable and locally advanced PDAC. The increasing success of modern poly-chemotherapy regimens (e.g., FOLFIRINOX, nab-paclitaxel, etc.) in the palliative and adjuvant setting, has also affected surgical treatment concepts of patients with (borderline) resectable, locally advanced as well as oligo-metastatic PDAC. Depending on the treatment aim, perioperative chemotherapy is defined as adjuvant, neo-adjuvant or palliative. While the definitions of adjuvant and palliative therapy are clear, preoperative therapies may be applied to achieve resectability in primarily unresectable disease, increase the R0-resection rate and decrease recurrence rates in borderline and primarily resectable tumors. In order to differentiate these situations, a differential definition of preoperative therapies into neoadjuvant (resectable), downEditorial