From systematic adjuvant chemotherapy in pancreatic cancer to personalized adjuvant chemotherapy: is the PANAMA score the solution?

Over the past decade, the management of pancreatic ductal adenocarcinoma (PDAC) has undergone a paradigm shift, with the growing adoption of neoadjuvant chemotherapy even in patients with resectable disease (1,2).

As this new standard raises questions regarding postoperative strategies, Rompen et al. offer a timely and relevant contribution by externally validating the PAncreatic NeoAdjuvant MAssachusetts (PANAMA) score, a practical prognostic model intended to estimate overall survival (OS) and to support decision making regarding adjuvant therapy following surgical resection (3).

The PANAMA score is based on four accessible postoperative variables: tumor size, lymph node status, resection margin status, and post-treatment carbohydrate antigen 19-9 (CA19-9) level. It stratifies patients into three risk categories: low [0–2], intermediate [3-5], and high [6-8].

In this multi-center European study, involving 383 patients across 31 centers, the score correlated significantly with OS and time to recurrence. Median OS reached 48.5 months in the low-risk group, 27.6 months in the intermediate group, and 22.3 months in the high-risk group. The time to recurrence also decreased with increasing score, indicating the score’s prognostic relevance despite its moderate discrimination (C-index 0.60).

Its performance, similar to that of the American Joint Committee on Cancer (AJCC) 8th edition staging system [area under the curve (AUC) 0.66 vs. 0.64] (4), reinforces the observation that purely clinico-pathological models have limited predictive capacity, a limitation already noted with other tools, such as the Amsterdam model (5).

Beyond prognostication, one of the most compelling contributions of this study lies in its evaluation of adjuvant chemotherapy benefit across the risk strata. The authors report no significant survival benefit in low-risk patients (P=0.15), while both intermediate and high-risk groups derived a meaningful survival gain (P=0.008 and 0.04, respectively).

Notably, this benefit was particularly evident in patients with R1 resections, larger tumors, or nodal involvement. These findings advocate for a selective use of adjuvant therapy and echo recent recommendations from the REDISCOVER 2024 consensus, which emphasized the importance of tailoring postoperative treatments to avoid unnecessary toxicity in low-risk patients (6).

However, this study is not without limitations. Despite its multi-center design, the inclusion of only 383 patients over six years, equivalent to approximately 12 patients per center, raises questions about statistical power and inter-institutional heterogeneity. Patient selection criteria, surgical techniques, and adjuvant chemotherapy protocols likely varied significantly between centers.

Moreover, in a substantial proportion of cases, the status of adjuvant chemotherapy was recorded as “unknown”, casting doubt on the reliability and completeness of the dataset.

The PANAMA score’s use of post-treatment CA19-9 as a prognostic marker aligns with contemporary guidelines (6).

Nonetheless, it overlooks an essential parameter: the kinetics of CA19-9. Numerous studies suggest that dynamic changes in CA19-9 levels provide more reliable insights into tumor biology and treatment response than absolute values alone (6). In line with recent observations, incorporating CA19-9 kinetics into future iterations of the model may enhance its predictive accuracy and offer a more nuanced reflection of treatment efficacy.

Another key limitation concerns CA19-9 non-secretors (defined as <5 U/mL), who were included in the scoring system. While this decision reflects real world practice, it also weakens its precision in this subgroup where CA19-9 is not informative (7,8). Alternative markers such as carcinoembryonic antigen (CEA) or cancer antigen 125 (CA125) have been suggested for evaluating tumor biology in such cases (6).

In a broader perspective, the study highlights the ongoing need for more biologically informed models. Innovative biomarkers like circulating tumor DNA (ctDNA) and patient-derived organoids may offer more refined strategies for predicting recurrence and therapy response in the near future (9-11). However, their limited availability in standard clinical settings reinforces the immediate clinical value of simple, pragmatic tools such as PANAMA.

Ultimately, the PANAMA score offers a valuable framework for stratifying postoperative risk and individualizing adjuvant therapy in PDAC patients treated with neoadjuvant FOLFIRINOX. Its strengths lie in its simplicity, accessibility, and immediate clinical applicability. However, its moderate predictive capacity, retrospective design, and lack of integration of molecular or kinetic biomarkers suggest that it should not be used in isolation.

Prospective validation in larger, more homogeneous cohorts, ideally through randomized trials, will be essential before its widespread adoption in clinical practice.

In this transitional era for PDAC management, where biology is increasingly guiding therapeutic decisions, the PANAMA score serves as a bridge between standard clinico-pathological evaluation and more refined biomarker-driven models. While not without limitations, it provides a valuable, structured framework for postoperative decision making in a complex patient population.

Importantly, its clinical utility does not reside in replacing judgment, but in informing it, helping multidisciplinary teams triage patients toward or away from additional systemic therapy. As we move toward precision oncology, tools like PANAMA should not be seen as endpoints, but as platforms upon which future models, integrating genomics, tumor biology and treatment kinetics, can be built. Until then, its judicious use, alongside expert clinical insight, may help deliver more balanced, individualized care for patients navigating the complex post-neoadjuvant landscape of PDAC.

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.