Predicting survival after surgery for pancreatic adenocarcinoma: Testing accuracy of current models.
Authors: Marcinak Clayton Thomas , Parker William F. , Burkard Mark E. , Parikh Alexander A. , Maithel Shishir K. , Kooby David A. , Kim Hong Jin , LeCompte Michael , Churpek Matthew , Zafar Syed Nabeel 
Published: June 2022

e16286

Background: Pancreatic adenocarcinoma (PDAC) remains highly morbid, and outcomes are difficult to prognosticate. Multiple models have also been developed to predict survival following surgical resection of PDAC, but their clinical utility remains unclear. This study aims to determine the accuracy of these algorithms for predicting PDAC survival. Methods: We performed a retrospective analysis using a de-identified dataset of patients who received neoadjuvant chemotherapy and underwent surgical resection of PDAC at four academic medical centers across the United States between 2010 and 2020. For this analysis the prognostic accuracy of the Memorial Sloan Kettering Cancer Center Pancreatic Adenocarcinoma Nomogram (MSKCCPAN) and the American Joint Committee on Cancer (AJCC) staging system were evaluated. For the MSKCCPAN, the prognostic index (PI) for each patient was calculated using the nomogram’s underlying Cox model. The PI was then used as input for the model’s survival function, which calculates the probability of DSS at 12-, 24-, and 36-month intervals. For the AJCC staging system, we assessed statistical discrimination between stage and DSS. We evaluated the concordance between predicted and actual DSS of both algorithms using the Uno C-statistic. Results: A total of 303 patients with complete information were included in the study, with 155 (51.2%) female patients and a mean age of 65.0 years (SD, 9.2 years). At the time of surgery, 47 (15.5%) patients had AJCC Stage IA disease, 45 (14.9%) had Stage IB, 49 (16.2%) had Stage IIA, 105 (34.6%) had Stage IIB, and 57 (18.8%) had Stage III. The median follow-up time of the cohort was 37.7 months (IQR, 16.4-70.7). One hundred eleven (36.6%) patients were alive at last follow-up, while 155 (51.2%) patients had died of disease. Thirty-seven (12.2%) patients died of another cause. The Kaplan-Meier estimated 12-, 24-, and 36-month DSS of the cohort was 74.3% (95% CI, 69.1-79.9), 46.6% (95% CI, 40.3-53.9) and 39.3% (95% CI, 32.9-46.9), respectively. The MSKCCPAN-predicted DSS at 12, 24, and 36 months was 78.1% (95% CI, 76.1-80.0), 56.4% (95% CI, 53.7-59.0), and 45.0% (95%0.781 CI, 42.3-47.6). For the MSKCCPAN, the calculated Uno C-statistic was 0.61 at 12 months and 0.62 at both 24 and 36 months. For the AJCC staging system, the Uno C-statistic was 0.61 at 12 months and 0.60 at both 24 months and 36 months. Conclusions: The present analysis suggests that concordance of current predictive models and staging systems with real world survival in patients with PDAC undergoing surgical resection after neoadjuvant chemotherapy has limited accuracy. Improving risk stratification of patients with PDAC will afford greater opportunities for tailoring patient selection, precision medicine initiatives, and trial design. There is an urgent need to develop novel models that better prognosticate outcomes following surgical resection of PDAC.