Pancreatic ductal adenocarcinoma remains one of the most formidable oncological challenges worldwide, requiring aggressive multimodal management. Recently, clinicians have increasingly utilized the PANAMA score in PDAC to estimate patient prognosis following neoadjuvant therapy. However, historical validation studies primarily evaluated tumours located within the pancreatic head, leaving distal lesions underrepresented. A landmark study published in the ANZ Journal of Surgery provides critical insights into the performance of this prognostic scoring tool specifically in patients undergoing distal pancreatectomy for pancreatic body and tail adenocarcinoma.

Clinical Context and the PANAMA Score in PDAC

Historically, surgical resection offered the only hope for long-term survival in pancreatic cancer. However, upfront resection often fails to address microscopic systemic dissemination. Consequently, multimodal treatment pathways now prioritize neoadjuvant chemotherapy or chemoradiation. Neoadjuvant regimens downstage tumours, sterilize regional lymph nodes, and identify patients with rapidly progressive disease who would not benefit from morbid surgery. Nevertheless, post-treatment prognostication remains difficult because preoperative therapies induce extensive histopathological alterations, including tissue necrosis and fibrous replacement.

To overcome these prognostic ambiguities, investigators developed the Pancreatic Neoadjuvant Massachusetts (PANAMA) score. This scoring system integrates histopathological parameters, including residual tumour stage, positive nodal burden, and surgical margin status, alongside post-treatment serum carbohydrate antigen 19-9 (CA19-9) levels. By combining both biochemical response and pathological response, the model categorizes patients into distinct low-, intermediate-, and high-risk survival tiers. Although researchers originally validated the score across broad surgical cohorts, tumours of the pancreatic head predominated in those initial evaluations. Tumours located in the pancreatic body and tail exhibit distinct anatomical, clinical, and molecular features. Therefore, clinicians urgently required independent validation specifically focused on distal resections.

Key Findings in Distal Pancreatectomy Following Neoadjuvant Therapy

The recent cohort study evaluated 52 patients with pancreatic body and tail adenocarcinoma who completed neoadjuvant treatment prior to undergoing distal pancreatectomy. Across the entire cohort, the median overall survival reached 40.8 months, whereas the median disease-free survival stood at 11.6 months. These findings underscore the tangible survival benefits that modern neoadjuvant regimens can deliver in surgically resected cohorts. More importantly, stratifying patients using the PANAMA risk criteria demonstrated clear prognostic divergence across risk tiers.

Specifically, patients classified into the high-risk category experienced significantly shorter median overall survival compared to their peers. High-risk patients achieved a median overall survival of only 21.8 months, whereas intermediate-risk patients achieved 31.1 months, and low-risk patients reached a remarkable 55.0 months. Furthermore, a parallel divergence emerged regarding disease-free survival. High-risk, intermediate-risk, and low-risk patients recorded median disease-free intervals of 10.3, 11.2, and 29.2 months, respectively. These statistically significant survival gradients confirm that the scoring algorithm successfully discriminates between favorable and aggressive post-neoadjuvant tumour biology following distal resection.

Comparing the PANAMA Score with Traditional AJCC Staging

Although the scoring algorithm demonstrated robust risk discrimination, investigators also benchmarked its performance against the conventional American Joint Committee on Cancer (AJCC) staging manual. Standard AJCC staging relies purely on anatomical depth of invasion, involvement of regional lymph nodes, and distant metastasis. Interestingly, in this specific distal pancreatectomy cohort, AJCC pathological staging outperformed the PANAMA model in predicting overall survival. Statistical concordance testing yielded a C-index of 0.70 for AJCC staging compared to 0.64 for the PANAMA framework.

This performance disparity invites critical evaluation from surgical oncologists and gastrointestinal specialists. In pancreatic head cancers, biochemical markers like CA19-9 often reflect relieved biliary obstruction alongside tumour response. However, distal lesions rarely cause early obstructive jaundice. Consequently, CA19-9 kinetics and postoperative thresholds may behave differently in body and tail lesions. Furthermore, distal pancreatectomy specimens generally yield different lymph node distributions compared to standard pancreaticoduodenectomy specimens. Because the PANAMA scoring model weights positive lymph node counts heavily, surgical variations in distal lymphadenectomy might alter the mathematical weighting of the score.

Pathological and Biological Differences in Distal Pancreatic Tumours

Pancreatic body and tail adenocarcinomas differ substantially from their proximal counterparts in presentation, genomic profiles, and surgical anatomy. Because distal lesions do not obstruct the common bile duct, patients rarely present with early symptoms such as jaundice or pruritus. Instead, these neoplasms grow silently over extended intervals, presenting as substantially larger masses that frequently abut major retroperitoneal vasculature or invade adjacent visceral organs like the spleen, stomach, or colon. Consequently, distal tumours often harbor greater genomic instability and higher rates of perineural or lymphovascular invasion.

Moreover, performing a distal pancreatectomy requires distinct technical considerations compared to a pancreaticoduodenectomy. Surgeons routinely perform concomitant splenectomy to achieve adequate lymphadenectomy along the splenic artery and vein. The unique lymphatic drainage pathways of the pancreatic body and tail can influence the ratio of recovered to positive lymph nodes. When clinicians apply post-neoadjuvant prognostic systems, these underlying biological and anatomical disparities directly impact accuracy. Thus, confirming that a prognostic scoring tool maintains validity in distal tumours represents a meaningful advance for personalized oncology.

Clinical Implications for Multidisciplinary Oncology Practice

In high-volume cancer centers across India and other emerging healthcare landscapes, oncologists increasingly adopt total neoadjuvant therapy for borderline resectable and locally advanced pancreatic cancer. Accurately assessing post-resection prognosis helps clinicians tailor subsequent adjuvant strategies, determine surveillance intervals, and conduct meaningful discussions regarding patient expectations. For example, high-risk patients identified by the scoring system experience early disease recurrence and shortened survival. Consequently, these individuals may benefit from accelerated post-resection imaging surveillance or intensified systemic maintenance therapies.

Conversely, patients exhibiting a low-risk profile achieve excellent median survival exceeding four years. For this subgroup, aggressive postoperative therapy must be carefully balanced against accumulated toxicities, neuropathy, and physical deconditioning caused by preoperative chemotherapeutic regimens. Multidisciplinary tumour boards should not rely exclusively on an isolated score. Instead, oncologists and surgical teams should evaluate the PANAMA classification in parallel with final AJCC pathological staging, baseline performance status, molecular sequencing, and surgical margin status. Integrating these complementary tools empowers clinicians to deliver truly personalized cancer care.

What components constitute the PANAMA score in PDAC?

The PANAMA score integrates four critical post-treatment clinicopathological variables. Specifically, the system evaluates post-neoadjuvant pathological tumour stage, the absolute number of positive regional lymph nodes, the microscopic surgical margin status, and the serum carbohydrate antigen 19-9 concentration recorded prior to surgical resection. By assigning weighted points to these factors, the score stratifies patients into low-, intermediate-, or high-risk prognostic categories to predict overall survival after surgery.

Why do body and tail pancreatic tumours require separate validation?

Pancreatic body and tail tumours exhibit distinct anatomical presentation, lymphatic drainage pathways, and underlying molecular biology compared to head lesions. Distal neoplasms rarely cause early jaundice and typically present at more advanced stages with larger dimensions. Because prior prognostic validation studies almost exclusively analyzed pancreatic head cancers treated with pancreaticoduodenectomy, independent validation was essential to verify that the scoring algorithm accurately stratifies distal lesions resected via distal pancreatectomy.

How should oncologists choose between AJCC staging and the PANAMA score?

Oncologists should view these two assessment frameworks as complementary rather than mutually exclusive tools. Although AJCC staging demonstrated slightly superior overall discrimination in this distal cohort, the PANAMA framework incorporates biochemical response via CA19-9 and margin clearance alongside anatomical depth. Multidisciplinary cancer teams can utilize AJCC staging for standardized anatomical classification while using the PANAMA risk tier to assess systemic recurrence risk and guide personalized postoperative surveillance.

Disclaimer: This content is for informational and educational purposes only and should not be considered professional medical advice. Always consult appropriate medical guidelines and specialists. Refer to the latest local and national guidelines for clinical practice.

References

1. Li S et al. Validation of the PANAMA Score in Patients With Pancreatic Ductal Adenocarcinoma Undergoing Distal Pancreatectomy. ANZ J Surg. 2026 Oct 04. doi: 10.1111/ans.70999. PMID: 42830225.
2. Hank T, Sandini M, Ferrone CR, et al. A Combination of Biochemical and Pathological Parameters Improves Prediction of Postresection Survival After Preoperative Chemotherapy in Pancreatic Cancer: The PANAMA-score. Ann Surg. 2022;275(2):e440-e448.
3. Rompen IF, Besselink MG, Hank T, et al. Validation of the PANAMA Score for Survival and Benefit of Adjuvant Therapy in Patients With Resected Pancreatic Cancer after Neoadjuvant FOLFIRINOX. Ann Surg. 2025;281(5):820-828.