Introduction
Pancreatic cancer is an aggressive malignancy with a poor prognosis (1,2). Approximately 80–85% of newly diagnosed patients present with either unresectable or metastatic disease, depriving them of the only potentially curative option-upfront surgical resection (1–3). Liver metastases are present in nearly 50% of cases and are associated with dismal outcomes, often measured in weeks to a few months (1). As a result, metastatic pancreatic cancer is generally considered untreatable.
Palliative chemotherapy provides modest survival benefit, with overall survival ranging from 8.5 to 10 months depending on the regimen used (1,2). The longest survival is observed with the FOLFIRINOX regimen (fluorouracil, folinic acid, irinotecan, and oxaliplatin) (1,2). In cases of locally advanced pancreatic cancer, FOLFIRINOX is employed with the aim of conversion to resectability, which has been achieved in up to 25.9% of patients (4).
However, in the metastatic setting, particularly with widespread liver involvement, conversion to surgery is not considered feasible, and no established treatment pathway exists. Rare cases demonstrating exceptional response to systemic therapy, such as the one presented here, remain anecdotal but raise important questions about tumour biology, treatment sequencing, and the future of personalized oncology in this disease.
Case report
In September 2018, a 60-year-old female was diagnosed with a poorly differentiated pancreatic body tumour and multiple liver metastases (Figs. 1 and 2). The patient initially presented at Derby Teaching Hospitals in United Kingdom and was referred to King's College Hospital, London, for tertiary Hepato-Pancreato-Biliary evaluation at a later stage.
The diagnosis was confirmed by endoscopic ultrasound-guided biopsy of the pancreatic mass. FOLFIRINOX chemotherapy was initiated in October 2018 with palliative intent. Given the radiological appearances strongly suggestive of liver metastases, no histological confirmation of the liver lesions was pursued, reflecting common clinical practice in the absence of features suggestive of sepsis or diagnostic doubt.
After 6 months of chemotherapy, in April 2019, imaging revealed significant response at both the primary site and within the liver, where lesions were now barely detectable (Fig. 3).
This finding persisted on serial imaging throughout continued systemic therapy and surveillance for more than two years. Subsequent FDG-PET imaging demonstrated no abnormal hepatic metabolic activity (Figs. 4, 5 and 6). At surgical exploration, no macroscopic liver lesions were identified, and therefore no intraoperative biopsies were performed.
By August 2019, following a total of 19 cycles of FOLFIRINOX, repeat imaging demonstrated near-complete resolution of both the pancreatic mass and hepatic metastases. The patient was subsequently enrolled in a clinical trial investigating a cancer vaccine and received two doses, administered four weeks apart. At her request, chemotherapy was paused.
The case was referred to the Hepato-Pancreato-Biliary (HPB) multidisciplinary team (MDT) at our tertiary centre for assessment of surgical resectability. Upon reviewing the initial and subsequent imaging, the MDT acknowledged the extraordinary radiological response. However, surgery was deemed inappropriate at that time due to the initial burden of hepatic metastatic disease. Surveillance under local oncology follow-up was recommended.
After a 15-month chemotherapy-free interval, restaging scans demonstrated sustained disease stability, leading to resumption of FOLFIRINOX in December 2020. The patient subsequently completed 12 additional cycles, with the final 4 cycles administered at a reduced dose (60%).
In June 2021, both CT and FDG-PET imaging confirmed complete radiological and metabolic response at both the primary and metastatic sites (Fig. 7). Following MDT discussion and given the sustained disease stability, the patient was deemed suitable for surgical exploration.
In August 2021, she underwent laparotomy. No macroscopic evidence of metastatic liver disease was identified intraoperatively. A left pancreatectomy with splenectomy was performed.
Final histopathology revealed a 20 mm pancreatic ductal adenocarcinoma arising in a 50 mm high-grade intraductal papillary mucinous neoplasm (IPMN) of pancreatobiliary subtype. There was infiltration of the splenic vein, and 1 of 9 resected peripancreatic lymph nodes contained metastatic disease. The pancreatic duct showed low-grade dysplasia at the margin, but there was no high-grade dysplasia or invasive cancer. Resection margins were negative. Final staging was ypT2 pN1 (1/9) LV1 PN0 R0. Representative haematoxylin and eosin-stained sections are shown in Fig. 8, demonstrating viable residual pancreatic ductal adenocarcinoma following systemic chemotherapy.
The postoperative course was uneventful.
The patient was monitored with 6-monthly interval CT scans. She did not receive further adjuvant chemotherapy. As of the most recent follow-up, she remains alive and disease-free 84 months (7 years) after her initial diagnosis and 4 years post-resection (Fig. 9). A timeline summarising the disease course is presented in Table I.
Discussion
Pancreatic cancer was the fourth leading cause of cancer-related deaths in the USA and Europe based on 2018 data and is projected to become the leading cause by 2030 (4). Metastatic pancreatic cancer (mPC) accounts for approximately 50% of cases at diagnosis, with a reported 5-year survival rate of just 3% in this group (4).
Invasive pancreatic cancer arising from intraductal papillary mucinous neoplasm (IPMN) has been shown to confer improved overall survival in resected patients, with 5- and 10-year survival rates of 72 and 62%, respectively (5). However, survival data specific to metastatic IPMN-associated pancreatic cancer remain unavailable, as these cases are typically grouped under the broader mPC category (5).
Long-term survivors with mPC are exceedingly rare and have been sparsely reported in the literature (6,7). FOLFIRINOX was the chemotherapeutic regimen used in most reported cases, although modifications, particularly reducing or omitting oxaliplatin, were often necessary due to adverse effects (7,8). One such survivor was BRCA1-positive with a history of multiple malignancies (7). In a striking case reported by Balta et al (6), multimodal treatment including chemotherapy, radiotherapy, transhepatic arterial chemoembolization (TACE), radiofrequency ablation (RFA) for a renal deposit, pancreaticoduodenectomy, liver wedge resection, Cyber-Knife radiosurgery, and repeated genomic analysis enabled nearly 5 years of survival. This underscores how a tailored combination of treatments can achieve prolonged survival and quality of life in a disease typically considered rapidly fatal.
While palliative chemotherapy does not conventionally aim for conversion, neoadjuvant therapy in borderline resectable or locally advanced pancreatic cancer seeks tumour downstaging to enable surgical resection. In this context, the role of pathologic complete response (pCR) remains controversial. pCR has been reported in approximately 4.8–10% of resected pancreatic adenocarcinoma cases following neoadjuvant chemotherapy (9–12), though its association with improved disease-free survival is inconsistent (11,12).
In the present case, pCR was not achieved; however, long-term disease-free survival was. This challenges the assumption that pCR is either necessary or predictive of prolonged survival. One report documented mPC with pCR and an additional six months of survival post-resection, in a patient treated with adjuvant monotherapy using the PARP inhibitor Olaparib (13). Similarly, mPC treated with FOLFIRINOX achieving both pCR and 5-year survival has also been described (8,14). Collectively, these cases suggest that pCR is not essential to survival outcomes and that achieving it should not be viewed as the primary goal.
The interpretation of an apparent complete hepatic response in mPC warrants careful consideration. In the case described here, while serial multiphasic contrast-enhanced CT and FDG-PET imaging demonstrated sustained absence of radiologically and metabolically detectable liver lesions in this case, current imaging modalities have recognised limitations in reliably excluding residual subcentimeter or microscopic disease, particularly following prolonged systemic chemotherapy. Treatment-related changes may render previously metastatic deposits radiologically occult or metabolically inactive, leading to underestimation of residual tumour burden. FDG-PET, although valuable for functional assessment, lacks sufficient sensitivity to definitively exclude microscopic viable disease, especially in the post-treatment setting.
Intraoperative assessment in this case was limited to systematic macroscopic inspection of the liver, and no intraoperative ultrasound or targeted biopsies were performed, as no suspicious lesions were identified on repeated imaging or at surgical exploration. Consequently, histological confirmation of complete metastatic clearance was not obtained, and the presence of occult residual disease cannot be entirely excluded. This represents an inherent limitation of the present study and reflects broader challenges in defining true complete response in metastatic pancreatic cancer.
In this context, the terms ‘vanishing liver metastases’ and ‘complete radiological regression’ are used descriptively to denote the durable absence of detectable hepatic disease on serial cross-sectional and metabolic imaging, rather than to imply histologically confirmed eradication. The prolonged stability of this response over several years of follow-up, together with favourable clinical outcome, underscores the exceptional nature of this case while acknowledging the limitations of current diagnostic techniques.
The present case represents a particularly remarkable and, to our knowledge, previously undescribed clinical phenomenon within mPC. While rare long-term survivors of mPC have been reported, this case is distinguished by the early and complete radiological disappearance of liver metastases after approximately six months of systemic chemotherapy, followed by sustained absence of detectable hepatic disease on serial cross-sectional and metabolic imaging over a prolonged period. Notably, this durable hepatic response persisted despite treatment interruptions and over several years of follow-up, an observation that challenges conventional expectations of metastatic pancreatic cancer biology. Whether immune-mediated mechanisms, potentially augmented by subsequent vaccine exposure, contributed to the long-term maintenance of this response remains speculative but biologically plausible.
The ACIT-1 trial is an early-phase clinical study investigating the safety and immunogenicity of a novel allogeneic cell-based cancer vaccine (ACIT-1) (15–17). Designed to stimulate host immunity against tumour-associated antigens, the trial included patients with late-stage solid tumours, including pancreatic cancer, using a dose-escalation strategy to balance immunologic response and toxicity (15–17).
While its clinical efficacy remains under investigation, our patient received two doses during a chemotherapy-free interval. Whether ACIT-1 contributed to disease control or to the favourable response observed during subsequent FOLFIRINOX administration is unclear. Importantly, the liver metastases had already shown significant response early in the first course of FOLFIRINOX. Robust conclusions on ACIT-1′s role await further data, and, to date, no peer-reviewed clinical outcome results have been published from this trial (NCT03096093) (16).
To our knowledge, this is the first reported case of mPC with initially extensive liver metastases demonstrating complete and sustained regression over the long term. This case is not only remarkable due to the radiological disappearance of liver disease but also because of the durable systemic response, raising the possibility of true cure, an outcome almost unheard of in the context of metastatic pancreatic cancer.
The convergence of favourable tumour biology, multimodal treatment strategies, and evolving molecular profiling to guide targeted therapies (e.g., immunotherapy, vaccines) may hold the key to improved outcomes in select cases. A deeper understanding of these components is critical to redefining the therapeutic landscape of this formidable malignancy.
In conclusion, this case illustrates a unique clinical course in which a patient with initially metastatic pancreatic cancer achieved sustained remission and underwent curative-intent resection following systemic chemotherapy. It challenges the long-held belief that metastatic pancreatic cancer is invariably terminal and highlights the importance of individualized, biology-driven treatment pathways. Rare though they may be, such cases underscore the need for continued exploration of predictive biomarkers and tailored therapeutic strategies that may convert inoperable disease into surgical candidates, ultimately improving survival and quality of life.