Evaluation of Adjuvant Chemotherapy Survival Outcomes Among Patients With Surgically Resected Pancreatic Carcinoma With Node-Negative Disease After Neoadjuvant Therapy

Abstract

ImportanceNeoadjuvant therapy (NAT) is rarely associated with a complete histopathologic response in patients with pancreatic ductal adenocarcinoma (PDAC) but results in downstaging of regional nodal disease. Such nodal downstaging after NAT may have implications for the use of additional adjuvant therapy (AT).ObjectivesTo examine the prognostic implications of AT in patients with node-negative (N0) disease after NAT and to identify factors associated with progression-free (PFS) and overall survival (OS).Design, Setting, and ParticipantsA retrospective review was conducted using data from 2 high-volume, tertiary care academic centers (University of Pittsburgh Medical Center and the Medical College of Wisconsin). Prospectively maintained pancreatic cancer databases at both institutes were searched to identify patients with localized PDAC treated with preoperative therapy and subsequent surgical resection between 2010 and 2019, with N0 disease on final histopathology.ExposuresPatients received NAT consisting of chemotherapy with or without concomitant neoadjuvant radiation (NART). For patients who received NART, chemotherapy regimens were gemcitabine or 5-fluoururacil based and included stereotactic body radiotherapy (SBRT) or intensity-modulated radiation therapy (IMRT) after all intended chemotherapy and approximately 4 to 5 weeks before anticipated surgery. Adjuvant therapy consisted of gemcitabine-based therapy or FOLFIRINOX; when used, adjuvant radiation was commonly administered as either SBRT or IMRT.Main Outcomes and MeasuresThe association of AT with PFS and OS was evaluated in the overall cohort and in different subgroups. The interaction between AT and other clinicopathologic variables was examined on Cox proportional hazards regression analysis.ResultsIn this cohort study, 430 consecutive patients were treated between 2010 and 2019. Patients had a mean (SD) age of 65.2 (9.4) years, and 220 (51.2%) were women. The predominant NAT was gemcitabine based (196 patients [45.6%]), with a median duration of 2.7 cycles (IQR, 1.5-3.4). Neoadjuvant radiation was administered to 279 patients (64.9%). Pancreatoduodenectomy was performed in 310 patients (72.1%), and 160 (37.2%) required concomitant vascular resection. The median lymph node yield was 26 (IQR, 19-34); perineural invasion (PNI), lymphovascular invasion (LVI), and residual positive margins (R1) were found in 254 (59.3%), 92 (22.0%), and 87 (21.1%) patients, respectively. The restricted mean OS was 5.2 years (95% CI, 4.8-5.7). On adjusted analysis, PNI, LVI, and poorly differentiated tumors were independently associated with worse PFS and OS in N0 disease after NAT, with hazard ratios (95% CIs) of 2.04 (1.43-2.92; P < .001) and 1.68 (1.14-2.48; P = .009), 1.47 (1.08-1.98; P = .01) and 1.54 (1.10-2.14; P = .01), and 1.90 (1.18-3.07; P = .008) and 1.98 (1.20-3.26; P = .008), respectively. Although AT was associated with prolonged survival in the overall cohort, the effect was reduced in patients who received NART and strengthened in patients with PNI (AT × PNI interaction: hazard ratio, 0.55 [95% CI, 0.32-0.97]; P = .04).Conclusions and RelevanceThe findings of this cohort study suggest a survival benefit for AT in patients with N0 disease after NAT and surgical resection. This survival benefit may be most pronounced in patients with PNI.

Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: A retrospective cohort study

“…Another recent retrospective study from two high-volume tertiary care academic centers, conducted by Hammad et al . 28 , looked at adjuvant therapy’s clinical benefit and impact in PDAC patients with node-negative disease after NAT and surgical resection. They discovered a survival benefit for adjuvant therapy in patients with N0 disease after NAT and surgical resection, which may be most pronounced in patients with perineural invasion.…”

The Survival Effect of Neoadjuvant Therapy and Neoadjuvant Plus Adjuvant Therapy on Different AJCC 8th TNM Stages: A Propensity Score Matching Analysis Based on SEER Database

“…Hammad [27] designed for N0 PDAC. However, none of the above studies were able to conduct strati ed analysis according to AJCC 8th TNM stages, in the current analysis, we found no survival bene t for NATAT in N0 diseases without metastasis compared to NAT, and not all pathologically con rmed nodepositive diseases may bene t from the additional AT after NAT, for NATAT only achieved a borderline survival bene t in patients with stage IIB (T1-3N1M0) compared to NAT (log-rank p = 0.087, multivariate Cox HR 0.815, p = 0.077, 0.649-1.022).…”

“…However, none of the above studies were able to conduct strati ed analysis according to AJCC 8th TNM stages, in the current analysis, we found no survival bene t for NATAT in N0 diseases without metastasis compared to NAT, and not all pathologically con rmed nodepositive diseases may bene t from the additional AT after NAT, for NATAT only achieved a borderline survival bene t in patients with stage IIB (T1-3N1M0) compared to NAT (log-rank p = 0.087, multivariate Cox HR 0.815, p = 0.077, 0.649-1.022). This may be owing to our inclusion of neoadjuvant radiotherapy (NART) along with other systemic therapies performed preoperatively as part of NAT, as Abdulrahman Y. Hammad demonstrated in their research that the impact of AT post-NAT was diminished in patients who underwent NART [27].…”

Biological risk based on preoperative serum CA19‐9 and histological grade predicts prognosis and improves accuracy of classification in patients with pancreatic ductal adenocarcinoma

“…For example, research has verified that patients with node‐negative (N0) pancreatic cancer may benefit from adjuvant therapy after neoadjuvant therapy and surgical resection. This survival benefit may be most pronounced in patients with perineural invasion 3 …”

“…This survival benefit may be most pronounced in patients with perineural invasion. 3 The American Joint Committee on Cancer (AJCC) tumornode-metastasis (TNM) staging system is the most commonly used classification for prognostic evaluation and treatment decisions in PDAC (Table 1). 4 The TNM classification has continuously improved to accurately reflect the current understanding of disease extent.…”