Neoadjuvant therapy versus upfront surgery followed by adjuvant chemotherapy in resectable or borderline resectable PDAC: a systematic review and meta-analysis of RCTs.

内容摘要

Adjuvant chemotherapy remains the standard of care following resection of pancreatic ductal adenocarcinoma (PDAC). However, despite advances with modern multi-agent regimens, most patients relapse, underscoring the need for alternative strategies. Neoadjuvant therapy offers several theoretical advantages, but evidence directly comparing it with upfront surgery remains limited. To compare efficacy and postoperative safety outcomes between neoadjuvant therapy and upfront surgery among patients with resectable or borderline resectable PDAC. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating outcomes in patients with resectable or borderline resectable PDAC treated with either neoadjuvant chemotherapy and/or chemoradiotherapy or upfront surgery followed by adjuvant chemotherapy. Outcomes of interest included overall survival, disease-free survival (DFS), R0 resection rate, and postoperative complication rates. Literature searches were performed in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, supplemented by clinical trial registries, conference abstracts, and gray literature. Study selection and data extraction were conducted independently by two authors. Sensitivity and subgroup analyses were performed to assess sources of heterogeneity. We included 13 RCTs, with one study excluded from the primary analysis due to high risk of bias. Neoadjuvant treatment did not confer a statistically significant benefit in overall survival (hazard ratio (HR) = 0.79; 95% confidence interval (95% CI), 0.58-1.10). However, neoadjuvant treatment was associated with improved DFS (HR = 0.79; 95% CI, 0.66-0.93) and a higher R0 resection rate (OR = 1.51; 95% CI, 1.04-2.19). There was no significant difference in the rate of major postoperative morbidity after resection (OR = 1.27; 95% CI, 0.61 - 2.62). Subgroup analyses revealed larger treatment effects in overall survival, DFS, and R0 resection rate in favor of neoadjuvant treatment among patients with borderline resectable PDAC. The survival advantage of neoadjuvant treatment in resectable or borderline resectable PDAC remains uncertain. Nonetheless, preoperative therapy improves DFS and R0 resection rates, with patients with borderline resectable disease deriving the greatest benefit. These findings should be interpreted with caution, given the limitations of the available evidence. Chemotherapy or radiotherapy before surgery compared with surgery first in pancreatic cancer: results from a review of clinical trials People with pancreatic cancer that can be removed by surgery usually receive chemotherapy after the operation to reduce the risk of the cancer coming back. However, many patients still experience disease relapse. Giving chemotherapy before surgery - the so called neoadjuvant therapy - might help by treating the cancer earlier and selecting patients who are more likely to benefit from surgery. To understand whether this approach works better than the traditional surgery-first method, we combined results from 13 randomized clinical trials that compared these two strategies. We looked at how long patients lived overall, how long they stayed free from cancer, how often surgeons achieved complete tumor removal (called R0 resection), and whether there were more surgical complications. The analyses showed that giving treatment before surgery did not clearly make people live longer overall. However, it did help patients stay free from cancer for a longer time and increased the chances of a complete tumor removal. The risk of serious surgical complications was similar between groups. Patients whose cancers were harder to remove (called borderline resectable) seemed to benefit the most from getting treatment before surgery. In summary, giving chemotherapy before surgery improves some important results and may be especially helpful for people whose tumors are harder to remove. However, it is still not clear whether this approach actually helps patients live longer. So far, the available studies have not shown a clear increase in overall survival, and more large, carefully conducted studies are needed to know for sure whether it truly extends life.