Introduction

Pancreatic cancer remains one of the most challenging malignancies to treat, with poor overall survival rates even when diagnosed at an early, potentially resectable stage. For patients with borderline resectable pancreatic cancer (BRPC), preoperative chemotherapy has emerged as a promising strategy to improve outcomes. This approach aims to downstage tumors, increase the likelihood of achieving negative surgical margins, and address potential micrometastases [1]. In recent years, there has been growing interest in the phenomenon of pathologic complete response (pCR) following preoperative therapy in pancreatic cancer. pCR, defined as the absence of viable tumor cells in the resected specimen, is associated with significantly higher overall survival compared to patients without pCR [2]. While relatively rare, occurring in approximately 4.8% of patients undergoing preoperative therapy followed by resection, pCR represents a potential paradigm shift in the management of BRPC [2]. Here, we present the case of a patient with BPRC who had no residual tumor during surgery after receiving neoadjuvant FOLFIRINOX chemotherapy.

Case

Ethical statements: This study was approved by the Institutional Review Board (IRB) of Kosin University (IRB No. 2024-10-020). Written informed consent was waived due to the retrospective nature of the study.

A 57-year-old male patient was hospitalized for abdominal pain and was referred to our hospital for recurrent pancreatitis. He was diagnosed with diabetes 25 years ago. HBA1c (glycated hemoglobin) was 8.5% A1c, indicating poor glycemic control recently. Alcohol consumption history was one bottle, 15 times/mo for 20 years, and smoking history was 1 pack/day for 25 years. He lost 7 kg in 1 month and had an ECOG-PS (Eastern Cooperative Oncology Group performance status) of 1. Vital signs were as follows: blood pressure of 120/70 mmHg; pulse of 98 beats/min; respiratory rate of 18 breaths/min; and temperature of 36.3 °C. On abdominal examination, bowel sounds were normal, there was no tenderness or rebound pain, and there was no palpable mass. Laboratory tests showed white blood cell count of 6,000/µL; hemoglobin of 13.9 g/dL; platelets of 158,000/µL. General chemical tests revealed a prothrombin time/activated partial thromboplastin time of 14.0 sec/36.1 sec; aspartate aminotransferase, 19 U/L; alanine aminotransferase, 10 U/L; alkaline phosphatase, 82 U/L; total bilirubin, 0.67 mg/dL; amylase, 78 U/L; lipase, 31 U/L; blood urea nitrogen, 15.0 mg/dL; creatinine, 0.85 mg/dL; and tumor marker testing showed carbohydrate antigen 19-9 (CA19-9), <2.00 U/mL and carcinoembryonic antigen (CEA), 4.32 ng/mL.

Chest radiography and chest computed tomography (CT) showed the absence of active lung lesions. Abdominal CT revealed diffuse enhancing wall thickening of the gallbladder and dilatation of the mid-pancreatic duct (Fig. 1A, 1B). Magnetic resonance cholangiopancreatography (MRCP) revealed focal nodular heterogeneous enhancement of the parenchyma, peripancreatic infiltration, and upstream main pancreatic duct dilatation with atrophy in the pancreatic head and body (Fig. 1C, 1D). The patient was followed up with CT and MRCP 3 months later because of recurrent groove pancreatitis and imaging findings that could not exclude the possibility of pancreatic cancer. Follow-up CT findings suggested pancreatic head-to-body cancer with peripancreatic infiltration and obstructive pancreatitis (Fig. 2A). On follow-up MRCP, the size of focal nodular heterogenous enhancement parenchyma in the head to the body of the pancreas increased to approximately 3.5–4.0 cm, suggesting pancreatic head-to-body cancer (Fig. 2B). Superior mesenteric vein (SMV)-portal vein encasement and tumor invasion were suspected and assessed as borderline resectable or more advanced cancers. Endoscopic ultrasound (EUS)-guided fine needle biopsy revealed a round, inhomogeneous, ill-defined hypoechoic mass with a diameter of approximately 2.9 cm in the head and uncinate process of the pancreas, accompanied by a dilated pancreatic duct; pancreatic adenocarcinoma was diagnosed on biopsy. The main pancreatic duct was dilated with an irregular contour and a hyperechoic wall. The pancreatic parenchyma showed hyperechoic foci with shadowing, stranding, and lobularity in a honeycomb pattern, suggesting the possibility of pancreatic cancer arising from chronic pancreatitis (Fig. 3). Positron emission tomography-CT performed for cancer staging revealed no abnormal F-18 fluorodeoxyglucose uptake (Fig. 4).

After a clinical diagnosis of T2N0M0, stage 1B (lesion size 29.9×27.1 mm on EUS/3.5–4.0 cm on CT, MR verbal reading) BRPC, modified FOLFIRINOX with irinotecan 180 mg/m², oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-fluorouracil 400 mg/m², and continuous infusion of 5-fluorouracil 2,400 mg/m² over 46 hours was administered every 2 weeks. Response was evaluated after the sixth cycle of chemotherapy. On abdominal CT, the ill-defined low-density mass in the pancreatic head decreased, leaving an oval-shaped small low-density mass, and pancreatic ductal dilatation decreased, showing partial remission after treatment (Fig. 5). On MRCP, stricture of the pancreatic duct was still observed, but the delayed-enhancing mass in the pancreatic neck had decreased in size and was not clearly visible; therefore, it was considered operable.

In a multidisciplinary general surgery consultation, the tumor was deemed resectable. Tumor marker tests remained low (CA19-9 <2.00 U/mL), but increased CEA (7.61 ng/mL). Robotic pylorus-preserving pancreaticoduodenectomy was performed. Histological examination confirmed the absence of visible tumor cells in the resected pancreas after chemotherapy. Only traces of necrotic tumor cells were observed (Fig. 6). The patient was discharged on postoperative day 32. He received three cycles of adjuvant modified FOLFIRINOX chemotherapy and is currently 6 months postoperative without recurrence.

Discussion

The achievement of pCR in BRPC following preoperative chemotherapy represents a major milestone in the treatment of this challenging disease. pCR is associated with improved overall survival, with some studies reporting a doubled 5-year overall survival rate of 63% compared to 30% in patients without pCR [1]. Other studies showed longer disease-free survival of 26 months compared to 12 months in a local recurrence group and a near complete response group [3]. Several factors have been identified as potentially associated with higher rates of pCR, which include the following: normalization of serum CA19-9, significant tumor shrinkage on imaging, and radiotherapy, particularly stereotactic body radiation therapy [1]. In contrast, the use of multiagent chemotherapy other than (modified) FOLFIRINOX was correlated with failure to achieve pCR [1,4].

Despite the positive implications of pCR, several challenges remain. Up to half of patients achieving pCR may still develop disease recurrence [1]. This highlights the need for ongoing surveillance and, potentially, adjuvant therapy even in cases of pCR. Accurately predicting pCR preoperatively remains challenging, as current imaging modalities may not reliably distinguish between residual tumor and treatment-related changes. Finally, the optimal neoadjuvant regimen to maximize pCR rates while minimizing toxicity has yet to be established.

To further improve outcomes for patients with BRPC, several areas warrant investigation. Identification of molecular or genetic markers that predict response to neoadjuvant therapy could help personalize treatment approaches. Development of more sensitive and specific imaging modalities could improve the accuracy of preoperative treatment response assessment. Exploration of novel combinations of chemotherapy, radiotherapy, and targeted agents may lead to higher pCR rates. Investigation of the role of immunotherapy in a neoadjuvant setting may offer new avenues for achieving pCR. In addition, prospective studies are needed to validate the factors associated with pCR and to establish standardized treatment protocols.

In conclusion, the achievement of pCR in BRPC represents a major advancement in this field. While it offers improved survival outcomes, challenges associated with recurrence risk and accurate preoperative prediction of pCR remain. Future research focusing on biomarkers, imaging techniques, and novel therapeutic combinations will be crucial in optimizing treatment strategies and improving long-term outcomes for patients with this devastating disease.

Here, we present the case of a patient with BPRC who had no residual tumor during surgery after receiving neoadjuvant FOLFIRINOX chemotherapy. He was hospitalized for abdominal pain and referred to our hospital for recurrent pancreatitis. Serum CA19-9 and CEA antigen levels were <2.00 U/mL and 4.32 ng/mL, respectively. Imaging studies suggested groove pancreatitis and possible pancreatic cancer, and mass formation was confirmed on follow-up CT and MRCP 3 months later. EUS-guided fine needle biopsy was performed to obtain the tissue, and histopathology confirmed a diagnosis of pancreatic ductal adenocarcinoma. Further evaluations, including positron emission tomography, revealed no evidence of metastasis. Finally, the patient was diagnosed with stage IB pancreatic cancer. The patient received six cycles of neoadjuvant FOLFIRINOX chemotherapy, and follow-up CT showed a decrease in the pancreatic mass and pancreatic ductal dilatation. Subsequently, surgery was performed, and no visible tumor cells were found on postoperative biopsy. He has been followed since discharge without recurrence, and future adjuvant chemotherapy is being considered.

The crucial aspect of this case is that the mass did not disappear after neoadjuvant chemotherapy, but SMV invasion of the vasculature disappeared; therefore, surgery was performed to completely remove the remaining mass, which had no residual malignant tissue. Pancreatic cancer is highly desmoplastic, which means that even if the cancer cells disappear, the mass often remains visible on imaging. This highlights the importance of deciding the point at which surgery should be performed. Furthermore, accumulation of case reports on pancreatic cancer with pCR can contribute to identifying mutational characteristics and factors related to chemotherapy response, which may yield significant breakthroughs in the treatment of pancreatic cancer.

Article information

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Author contributions

Conceptualization: JWL. Data curation: SHK. Formal analysis: JWL. Funding acquisition: JWL. Investigation: SHK. Methodology: JWL. Project administration: JWL. Resources: SHK. Software: SHK. Supervision: JWL. Validation: SHK. Visualization: SHK. Writing-original draft: SHK. Writing-review & editing: JWL. All authors read and approved the final manuscript.

Fig. 1.

Liver computed tomography (CT) images. (A, B) Liver dynamic CT showing diffuse enhancing wall thickening of gallbladder and dilatation of mid-pancreatic duct. Groove pancreatitis cannot be ruled out due to fluid accumulation in the peripancreatic groove (green arrow). Magnetic resonance cholangiopancreatography (MRCP) images. (C, D) MRCP showing focal nodular heterogeneous enhancement parenchyma, peripancreatic infiltration and upstream main pancreatic duct dilatation with pancreas atrophy in the pancreatic head and body.

Fig. 2.

Follow-up computed tomography performed 3 months later. (A) Heterogeneous mass suggestive of head-to-body pancreatic cancer is seen (white arrow). Superior mesenteric vein-portal vein encapsulation is suspected (red arrow). Follow-up magnetic resonance cholangiopancreatography performed 3 months later. (B) Increased size of focal nodular heterogeneous enhancement parenchyma in the head to the body of the pancreas (green arrow) is seen.

Fig. 3.

(A) Endoscopic ultrasound (EUS) showing a round, inhomogeneous, hypoechoic mass with a diameter of approximately 2.9 cm in the head and uncinate process of the pancreas, accompanied by a dilated pancreatic duct. EUS-guided fine needle biopsy was done. (B) Biopsy showing atypical glands with diffuse fibrosis, which was diagnosed as pancreatic ductal adenocarcinoma (hematoxylin and eosin stain, ×100).

Fig. 4.

Positron emission tomography-computed tomography (PET-CT) images. PET-CT showing no abnormal F-18 fluorodeoxyglucose uptake. (A) Axial and (B) coronal views.

Fig. 5.

Computed tomography after neoadjuvant chemotherapy. The ill-defined low-density mass in the head of the pancreas is reduced, leaving a small low-density oval mass (yellow arrow).

Fig. 6.

Pylorus-preserving pancreaticoduodenectomy was performed. (A) Gross pathology photo of the surgical specimen. (B) No visible tumor cells are detectable in the resected pancreas after chemotherapy. Only traces of where necrotic tumor cells once existed are seen (arrow) (hematoxylin and eosin stain, ×100).

References

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• 2. Stoop TF, Oba A, Wu YH, Beaty LE, Colborn KL, Janssen BV, et al. Pathological complete response in patients with resected pancreatic adenocarcinoma after preoperative chemotherapy. JAMA Netw Open 2024;7:e2417625.ArticlePubMed
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• 4. Rajagopalan MS, Heron DE, Wegner RE, Zeh HJ, Bahary N, Krasinskas AM, et al. Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer. Radiat Oncol 2013;8:254.ArticlePubMedPMCPDF

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