FOLFIRINOX versus gemcitabine (plus paclitaxel) for pancreatic cancer—an analysis based on data from the Clinical Cancer Registry of Lower Saxony

Introduction

Background

Pancreatic cancer (PC) poses major challenges to medicine due to the disease’s resistance to therapy (1). At the same time, the incidence of PC is increasing (2) and it is set to become the second leading cause of tumour-related deaths in Germany (3) and the US by 2030 (2). Symptoms of PC are often subtle and nonspecific, resulting in late detection and consequently, the lowest survival rate among all cancer types globally (4).

Despite intensive efforts in both basic and clinical research, only minor improvements in median survival during the palliative stage [Union for International Cancer Control (UICC) stage IV] of the disease have been achieved to date (4).

Gemcitabine (Gem) monotherapy has long been considered the standard treatment for advanced PC due to its favorable toxicity profile. FOLFIRINOX, a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin, was later introduced as a more intensive regimen, typically reserved for patients with good performance status. Clinical trials show that treatment with FOLFIRINOX is superior to treatment with gemcitabine plus paclitaxel (Gem + Pac) or Gem alone for PC (5,6). In addition, evidence of clinical studies (7) shows that the administration of Gem + Pac for patients with metastatic PC in stage IV is superior to Gem alone, especially in terms of overall survival.

These findings are reflected in the German S3 Guidelines for Exocrine Pancreatic Cancer (version 2.0), which are based on clinical trial evidence (5-7). The guidelines are intended to assist German physicians in making treatment decisions. They recommend FOLFIRINOX in the adjuvant setting (GL. 7.5), and either FOLFIRINOX or Gem + Pac over Gem alone in the palliative setting when Eastern Cooperative Oncology Group (ECOG) status, comorbidities, and patient preference allow (GL. 8.11, GL. 8.13) (4).

Rationale and knowledge gap

Several real-world studies have investigated outcomes of chemotherapy regimens in patients with advanced PC outside of clinical trials. For example, Chiorean et al. (8) systematically reviewed 34 retrospective studies comparing FOLFIRINOX and Gem + Pac. They found no consistent survival differences between the two regimens but noted methodological limitations such as selection bias, varying study quality, and incomplete clinical data (e.g., ECOG status, comorbidities). Similarly, Santucci et al. (9), using data from the prospective PURPLE registry in Australia and New Zealand, reported comparable overall survival between FOLFIRINOX and Gem + Pac. However, their study included a smaller FOLFIRINOX subgroup and focused primarily on sequencing strategies in advanced disease, without broader population-level inclusion.

Building on this work, our study uses comprehensive registry data from Germany to include all patients reported with PC in a defined region, regardless of treatment regimen or clinical trial eligibility. To capture the full spectrum of treatment patterns, we compared groups receiving FOLFIRINOX, Gem exclusively, Gem + Pac, other chemotherapy regimens, or no reported chemotherapy. This approach allows for a more inclusive view of real-world care and helps to describe outcomes beyond the selected subgroups commonly found in both clinical studies and previous real-world analyses (8,9), which typically focused on a limited set of regimens.

While clinical trials have established the superiority of FOLFIRINOX and Gem + Pac over Gem monotherapy (5,6), it remains unclear to what extent these benefits translate into routine clinical practice, where patient populations are more diverse, and treatment conditions may vary. Additionally, existing clinical studies often exclude patients who receive alternative or no chemotherapy regimens, leaving a significant gap in understanding the outcomes of these groups.

Moreover, there is limited evidence on the extent to which adherence to the S3 guideline recommendations, which are based on clinical study results, impacts survival outcomes in real-world settings. Addressing this knowledge gap is critical to assess the effectiveness of guideline-compliant care and to ensure that the benefits demonstrated in clinical trials are realized in everyday clinical practice.

Objective

The primary objective of this study is to examine whether positive effects on survival can be shown using real-world data from the Lower Saxony Clinical Cancer Registry (Germany) and additionally assessing whether, and to what extent, guideline-compliant care following the S3 guideline based on evidence generated from various clinical studies positively impacts survival in a real-world setting. We present this article in accordance with the RECORD reporting checklist (https://apc.amegroups.com/article/view/10.21037/apc-24-36/rc).

Methods

Data

While real-world studies are commonly conducted using insurance databases, we use German cancer registry data on cancer diagnoses that are documented in an oncological basic data set (oBDS) (10). This oBDS comprises essential clinical information, including patient demographics (age, gender), tumor diagnosis [International Classification of Diseases (ICD) classification, tumor-node-metastasis (TNM) staging, tumor localization], detailed treatment data (therapy type, surgery, chemotherapy, radiotherapy) and follow-up outcomes (survival status, recurrence). The oBDS also includes fields for ECOG performance status, but this variable was not yet sufficiently populated during the study period, particularly in the early years after registry implementation, to be used reliably in the survival analysis. Comorbidity data are not systematically collected in the cancer registry but may be available in the future through linkage with health insurance data. Given these constraints, from this dataset (oBDS), we specifically utilize the variables of tumor-node-metastasis (TNM) staging, age, gender, surgical intervention with the intention of tumor resection, the chemotherapy drug regimen, and the follow-up outcome survival. The basic unit of the dataset is the person to whom at least one tumor element is assigned. This must contain a primary diagnosis and optionally information on treatment and subsequent events such as remissions and recurrences.

Because the cancer registry serves to ensure the quality of medical care for people with cancer with precisely this data and claims data does not contain this information, our data provides a more suitable source for treatment research than claims data.

The Clinical Cancer Registry of Lower Saxony (KKN) was founded in 2017 and mandatory reporting by all physicians and dentists practicing in Lower Saxony commenced on 1 July 2018, in accordance with Section 5 [1] of the Act on the Clinical Cancer Registry of Lower Saxony (GKKN). All data is derived from mandatory reporting and information is available at both the reporting and tumor levels. Patients who are not at least 18 years old at the time of diagnosis are not reportable.

As of June 30th, 2023, data on 9,281 patients (9,309 tumours) with pancreatic carcinoma as diagnosis according to the ICD-10 (11), starting with the diagnosis C25, have been available at the KKN since the start of the reporting obligation on July 1st, 2018.

Study population

As of June 30th, 2023, the cancer registry contained data on 9,281 patients diagnosed with pancreatic carcinoma (ICD-10 code C25). For our analysis, we included the 5,165 patients who were newly diagnosed between January 1, 2019 and December 31, 2021. Patients diagnosed in 2018 were excluded due to the registry’s initial setup phase and incomplete data quality. The cutoff at the end of 2021 ensures an adequate follow-up period for survival analysis. Besides, we exclude patients with endocrine PC (ICD-10 C25.4) and with multiple pancreatic tumors in order to keep the patient group homogeneous and comparable in these characteristics. Patients with incomplete information relevant to our analysis were excluded. In addition, patients are excluded when only reports from doctors outside Lower Saxony were documented.

In our statistical analysis, we first consider all patients. In our Cox regression, patients with only FOLFIRINOX, Gem or Gem + Pac, as well as with another chemotherapy regimen (see Table S1 for a full list) or no chemotherapy are considered. The focus in the interpretation of our results is on the chemotherapy regimens only FOLFIRINOX, Gem and Gem + Pac considered in the clinical trials (5-7).

The fact that the group with other chemotherapy regimens includes patients who received more than one chemotherapy regimen is taken into account in the discussion regarding the limitations of our results and limits the comparability to the three groups with only FOLFIRINOX, Gem or Gem + Pac, because the comparison would otherwise be based on an immortal time bias (12). Immortal time bias can occur when patients who receive two treatments are falsely attributed a longer survival time during the period leading up to the second treatment (during which they must necessarily survive to receive the second treatment) than patients who have received only one treatment.

The three groups with only FOLFIRINOX, Gem or Gem + Pac are therefore easier to compare with each other because, on the one hand, they have already been discussed in the literature and, on the other hand, the administration of only one chemotherapy substance makes them less likely to be subject to the problem of immortal time bias in a comparison with each other. Therefore, we focus on these three groups in our interpretation.

Study design

This retrospective, registry-based observational study is designed as a comparative effectiveness analysis using a non-randomised design with adjustment for confounders.

Statistical analysis

Demographic and clinical characteristics of the sample are summarized as proportions for categorical variables and as means with standard deviations for continuous variables.

Survival time is defined as the interval between the date of diagnosis and either the last recorded physician contact in Lower Saxony or the patient’s death. Therefore, patients are censored if they switch to a treating physician outside of Lower Saxony respectively become untraceable or if the last recorded contact is before the end of the observation period (3 years).

Kaplan-Meier curves are used to visualize survival probabilities at 1, 2, and 3 years, and to calculate median survival times. Differences in survival times between groups are assessed using the log-rank test (13).

Results are presented both for the entire sample and stratified by treatment group.

We calculate the 1-, 2- and 3-year survival rates and the median survival by using Kaplan-Meier estimates and assess the HR of death by using multivariate Cox-regression (14). The confidence interval for the median survival and HR is calculated at a 5% significance level. To validate the results the proportional hazards assumption was tested via visual inspection of survival curves, as recommended by Zwiener et al. (15). For this assumption the ratio of hazard rates between two groups must be constant over time (15).

Overall survival time is presented, showing the differences between the three drug regimen FOLFIRINOX, Gem and Gem + Pac. Additionally, the group of patients without chemotherapy regimen is also shown. Due to the great heterogeneity of person with other chemotherapy treatments and the resulting limited information on survival times, this group is not represented in the Kaplan-Meier curves.

The covariates included in the Cox regression are UICC stage, age, gender, surgery with the intention of resection [see German Procedure Classification Operation and Procedure Codes (OPS)-Codes in Table S2] and the drug regimen used in chemotherapy. ECOG performance status was not included due to insufficient data availability during the study period.

Subgroup analyses were conducted for patients in UICC-stage IV. We use the presentation of patients in UICC-stage IV to ensure comparability to studies in palliative setting (6,7) using patients receiving the drug regimen FOLFIRINOX, Gem and Gem + Pac. The survival times of the patients are also comparable when only considering UICC stage IV, as the guidelines recommend all substances (FOLFIRINOX, Gem, and Gem + Pac) in palliative therapy, while in adjuvant therapy for stages I–III, FOLFIRINOX or Gem is recommended. Therefore, when considering only the characteristic of chemotherapy regimen, patients in stage IV could have been treated in accordance with the guidelines using all three substances (see Figure S1).

However, due to the limited availability of ECOG performance status and the lack of comorbidity data in the cancer registry, it was not feasible to directly determine whether individual patients were eligible for a specific guideline-recommended regimen. Therefore, treatments are not classified as “guideline-adherent” on a case-by-case basis. Instead, we analyse overall treatment patterns and their associations with survival as an indirect reflection of guideline implementation in real-world settings—particularly for stage IV patients, for whom all three therapies are potentially guideline-conform, although the guideline explicitly recommends FOLFIRINOX or Gem + Pac over Gem monotherapy when clinically appropriate.

A confidence level of 95% is used unless otherwise specified.

The statistical program R version 4.2.2 (16) was used in the analyses and the creation of graphs and tables. The survival analyses were conducted using the “survminer” package. The data can be requested in accordance with § 20 GKKN and could then be replicated. Besides the R code can be made available on request.

Results

A total of 5,165 patients with a diagnosis of PC were identified in the period from January 1, 2019 to December 31, 2021 (Figure 1). These patients have a diagnosis beginning with the ICD-10 code C25 and refer to the data status of the KKN as of June 30, 2023.

Figure 1 Flowchart. ^†, exclusion for various reasons n=808: n=753, exclusively pathological data; n=45, no plausible or too few data; n=0, not at least 18 years at the time of diagnosis; n=1, gender neither male nor female; n=9, time of treatment or diagnosis after death.

From this population (Figure 1), 1,246 patients were excluded: 24 patients with a diagnosis of pancreatic endocrine tumour (ICD-10 C25.4), 11 patients with multiple pancreatic tumours, and 808 patients due to various reasons. This group included patients with exclusively pathological reports (n=753), insufficient or implausible information (n=37), documentation of diagnosis or treatment only after death (n=9), and missing gender classification (n=1). In addition, 403 patients were excluded because they were reported exclusively by physicians located outside Lower Saxony.

After applying our inclusion and exclusion criteria (see Figure 1), 3,919 patients were included in the study population. Based on this population, chemotherapy regimen was documented in the registry for 55% (n=2,152) of patients. Out of those, 21% (n=458) received chemotherapy with FOLFIRINOX, 17% (n=362) received chemotherapy with Gem, 24% (n=506) received chemotherapy with Gem + Pac and 38% (n=826) received other chemotherapy regimen (see Table 1).

Table 1 shows that the FOLFIRINOX group and the group that received other or more than one chemotherapy regimen are on average younger than the Gem or Gem + Pac groups or those who did not receive chemotherapy. The age distribution by gender is also shown graphically in Table S3. This shows that proportionately more women in the older age groups were diagnosed with PC than men.

Table 1 shows that in this population, more men are diagnosed with exocrine PC than women. Additionally, when a UICC stage is documented, most patients are diagnosed at UICC stage IV. The majority of UICC stage IV patients, in relative terms, are assigned to the Gem + Pac group. The highest number of undetermined UICC stages is found in patients who either received the Gem + Pac regimen or had no documented chemotherapy. Furthermore, only one-third of patients were assigned an ECOG performance status at diagnosis, while two-thirds were not. Among the third of patients documented as having undergone surgery with the intention of resection, the fewest operations are reported in the Gem + Pac group.

Figure 2 and Table S4 show the 1-, 2-, and 3-year survival rates for patients with FOLFIRINOX are 52% (95% CI: 47–57%) 30% (95% CI: 25–36%), and 21% (95% CI: 16–27%), with a median survival of 12 months (95% CI: 11–15). For Gem, the rates are 38% (95% CI: 33–43%), 16% (95% CI: 12–21%), and 13% (95% CI: 9–18%), respectively, with a median survival of 9 months (95% CI: 8–10). Patients receiving Gem + Pac have survival rates of 30% (95% CI: 26–34%), 10% (95% CI: 8–14%), and 3% (95% CI: 1–6%), with a median survival of 8 months (95% CI: 7–9), while those no recorded CT treatment have rates of 22% (95% CI: 20–24%), 11% (95% CI: 10–13%), and 7% (95% CI: 6–9%), with a median survival of 3 months (95% CI: 3–4).

Figure 2 Kaplan-Meier curves (36 months) by treatment group, including patients with non-recorded CT. CT, chemotherapy; FOLFIRINOX, 5-fluorouracil + leucovorin + irinotecan + oxaliplatin; Gem, gemcitabine; Gem + Pac, gemcitabine plus paclitaxel; NA, not available.

Figure 3 and Table S5 show the survival time of patients in UICC stage IV by treatment group. Patients in UICC stage IV who have not received any drug regimen are also shown as a reference. The 1-, 2- and 3-year survival rates for patients with FOLFIRINOX are 35% (95% CI: 28–44%), 5% (95% CI: 2–12%) and 5% (95% CI: 2–12%) with a median survival of 9 months (95% CI: 7–11). Patients with Gem have a 1-, 2- and 3-year survival rate of 13% (95% CI: 7–23%), 0% (95% CI: –) and 0% (95% CI: –) and a median survival of 5 months (95% CI: 4–6). For patients with Gem + Pac and patients without drug, the 1-, 2- and 3-year survival rates are 23% (95% CI: 18–30%), 4% (95% CI: 2–8%), and 2% (95% CI: 1–6%), and 7% (95% CI: 5–10%), 1% (95% CI: 1–4%) and 0% (95% CI: –) respectively, with a median survival of 7 months (95% CI: 6–9) for patients with Gem + Pac and 2 months (95% CI: 2–2) for patients without drug.

Figure 3 Survival curves (36 months), by drug regimen in UICC stage IV. FOLFIRINOX, 5-fluorouracil + leucovorin + irinotecan + oxaliplatin; Gem, gemcitabine; Gem + Pac, gemcitabine plus paclitaxel; NA, not available; UICC, Union for International Cancer Control.

The results of the Cox regression comparing FOLFIRINOX to Gem, Gem + Pac, other chemotherapy (CT) and no CT adjusting for UICC-stage, age, gender and whether surgery was performed are presented in Table 2. For all characteristics except gender, the log-rank test indicates that the survival time within the characteristics differs at least at the 5% significance level. The propotional hazard assumption was assessed through visual inspection.

The multivariable Cox regression in Table 2 shows, risk of death increases with higher UICC stage, and age, while surgery with intention of resection is associated with a lower risk, ceteris paribus.

In addition, patients treated with FOLFIRINOX had a significantly lower hazard of death compared to those treated with Gem monotherapy (HR 1.27, 95% CI: 1.06–1.52, P<0.001), followed by those who received Gem + Pac (HR 1.20, 95% CI: 1.03–1.41, P<0.001), highlighting the survival benefit associated with guideline-recommended regimens. Compared to FOLFIRINOX, the HR was 0.74 (95% CI: 0.64–0.86, P<0.001) for patients receiving other chemotherapy regimens and 2.29 (95% CI: 2.00–2.63, P<0.001) for patients without documented chemotherapy.

Discussion

Key findings

This study assessed whether survival benefits demonstrated in clinical trials translate into real-world outcomes using data from 3,919 patients with PC in the Lower Saxony Clinical Cancer Registry (2019–2021). Patients received chemotherapy with FOLFIRINOX (n=458), Gem (n=362), Gem + Pac (n=506), other regimens (n=826), or no documented chemotherapy (n=1,767) (see Table 1).

Among the three main regimens, patients treated with FOLFIRINOX had the highest survival. Compared to this group, the hazard of death was 27% higher (HR 1.27, 95% CI: 1.06–1.52, P<0.001) and 20% higher for Gem + Pac (HR 1.20, 95% CI: 1.03–1.41, P<0.001). In UICC-stage IV median overall survival was 9.0 months for the FOLFIRINOX group (95% CI: 6.8–11.0), 4.5 months for the Gem group (95% CI: 3.7–6.1) and 7.2 months (95% CI: 5.7–8.6) for the Gem + Pac group, supporting the guideline recommendation (GL. 8.11, 8.13) of more intensive regimens in eligible patients.

Patients receiving other chemotherapy regimens had a lower adjusted risk of death (HR 0.74, 95% CI: 0.64–086, P<0.001), while those without documented chemotherapy had substantially higher mortality (HR 2.29, 95% CI: 2.00–2.63, P<0.001), although both groups were highly heterogeneous and were only marginally included in the interpretation.

Comparison with similar research

The recommendation GL. 7.5 in adjuvant therapy and the recommendations GL. 8.11 in palliative therapy from the S3 guidelines, which are based on the findings of clinical studies (5,6) and recommend FOLFIRINOX when the ECOG status, comorbidity, and patient preference allow, are reinforced by our study.

Our finding are furthermore consistent with the studies by Conroy et al. (5,6), which found a survival advantage of FOLFIRINOX compared to Gem as both a first-line (HR 0.64, 95% CI: 0.48–0.86, P=0.003) and palliative treatment (HR 0.57, 95% CI: 0.45–0.73, P<0.001). We use FOLFIRNOX as the reference group in our Cox-Regression in contrast to the studies by Conroy et al. (5,6) using Gem as the comparison group. Despite this difference of the different comparison group in the multivariable Cox regression, the directions of the effect when administering the chemotherapy Gem compared with FOLFIRINOX and vice versa, expressed by the HRs, are comparable.

The survival benefit of Gem + Pac over Gem, particularly in the palliative situation in UICC stage IV, is shown in 3 and Table S5 as a subgroup analysis and is also found in the literature by von Hoff et al. (HR 0.72, 95% CI: 0.62–0.83, P<0.001) (7). The recommendation GL. 8.13 in palliative therapy from the S3 guidelines, which is based on the findings of this clinical study (7) and recommends Gem + Pac instead of Gem alone when the ECOG status, and patient preference allow, is thus reinforced by our study.

When no chemotherapy regimen was documented for patients, the risk of death was 2.29 times higher compared to the FOLFIRINOX group (HR 2.29, 95% CI: 2.00–2.63, P<0.001), but this subgroup has not been discussed in the literature.

Implications

The findings of this study underscore the importance of considering FOLFIRINOX as the preferred chemotherapy regimen for PC when ECOG status, comorbidity, and patient preference permit, as it shows the trend of superior survival outcomes compared to Gem and Gem + Pac. Additionally, our findings indicate that in terms of survival, the chemotherapy regimen Gem + Pac should be preferred over Gem alone, especially in the palliative setting (UICC stage IV). These insights are consistent with those of the clinical studies (5-7) that form the basis of the S3 guidelines, which in turn guide decision-making for physicians in Germany regarding therapies.

Our analysis expands on these clinical findings (5-7) by including a broader range of patient groups, specifically those receiving no chemotherapy as well as those treated with regimens beyond the three standard options. This broader inclusion enables a more comprehensive understanding of treatment practices and outcomes in routine clinical care, beyond the controlled environment of clinical trials.

The results of our study also highlight the value of cancer registry studies as a complement to clinical studies due to the larger number of cases and can also demonstrate the effectiveness of guidelines and treatment lines in real world care. While the clinical studies that investigate the relationship between FOLFIRINOX, Gem, and Gem + Pac examine populations from across Europe, North America, or Australia, our study is the first to present results from Germany on that relationship.

Moreover, the findings from our registry-based analysis expand the existing real-world evidence provided by prior studies (8,9) by offering a comprehensive perspective from the German context. In addition to focusing on the three most relevant chemotherapy regimens FOLFIRINOX, Gem, and Gem + Pac, our study includes all reported PC cases within a defined population. This broader inclusion enhances the generalizability of our findings and complements the international literature with population-level insights from Germany.

Strengths and limitations

The strength of this study lies in its large sample size as well as the diversity of included participants (17), while registry studies are generally considered to provide a lower level of evidence than randomized controlled trials (RCTs). While registry studies are generally considered to provide a lower level of evidence than RCTs, their strengths (17) include a large sample size as well as the diversity of included participants. We show that, the population of our study, even when considering only the 1,326 patients who received a chemotherapy regimen with the groups FOLFIRINOX (n=458), Gem (n=362) and Gem + Pac (n=506), is larger than that of the two studies by Conroy et al. (5,6) with 493 patients and 342 patients who received FOLFIRINOX or Gem equally distributed. By additionally considering patients with Gem + Pac, other CT regimen and no chemotherapy in a state-wide register, thus we extend the available clinical studies to reflect the full “real world” landscape of treatment for PC.

Moreover by focusing exclusively on Germany, our study provides a localized perspective that complements existing international studies (5-7), which primarily draw from populations in whole Europe, America, and Australia or patients almost exclusively in France. The results of the international clinical studies from various countries, which correspond to the results of our work with registry data from Germany, strengthen the external validity of our results and the results to date.

However, there are some limitations to consider. Information not included in the dataset may limit the conclusions. This particularly applies to patient preferences, pre-existing conditions, and toxicity. Another key limitation relates to the incomplete documentation of ECOG performance status and the absence of structured comorbidity data in the cancer registry during the study period. Although the registry contains a dedicated field for ECOG, it was not yet sufficiently populated to be used reliably for analysis. Consequently, it was not feasible to determine on an individual level whether a given patient was eligible for a guideline-recommended regimen based on clinical fitness. Our analysis therefore does not assess guideline adherence on a case-by-case basis, but instead uses treatment patterns and associated survival outcomes as an indirect indicator of real-world implementation. This approach is particularly applicable to patients in UICC stage IV, where all three regimens FOLFIRINOX, Gem, and Gem + Pac can be considered guideline-conform, although the guidelines clearly recommend FOLFIRINOX or Gem + Pac over Gem alone when patient fitness allows.

A further limitation concerns the group of patients for whom no chemotherapy regimen was documented. The results of the Cox regression regarding the group for which no chemotherapy regimen was documented are probably not very reliable, as the reason for the lack of documentation is not available to the registry (e.g., not transmitted information by the inpatient or outpatient sector). Although the addition of this group serves to provide a complete view of all patients treated with PC in Lower Saxony and thus offers added value compared to existing clinical trials that selectively look at individual study arms, this group has a low probability of survival from the outset, as these patients include patients who did not have the opportunity to receive a chemotherapy regimen at all because they had previously died. There is therefore a possibility of an immortal time bias, both in the group without documented chemotherapy and in the heterogeneous group receiving other chemotherapy regimens (see Table S1). Due to the unclear reasons regarding the lack of documentation of the chemotherapy regimen, this group was only marginally considered in the interpretation. A further constraint is potential censoring bias from patients who moved out of state or became untraceable during follow-up.

Another limitation arises from the observational period of the study. In our study we only calculated 1-, 2-, and 3-year survival rates for patients diagnosed between January 1, 2019 and December 31, 2021. Nevertheless, most patient characteristics relevant to this work, such as an operation or therapy performed, or the events of doctor contact/treatment or death, should be recorded within the observation period of this work. This is supported by studies, such as those by Kuhlmann et al. (2004), Lim et al. (2003), Egawa et al. (2012), and Distler et al. (2013) (18-21), which consider 5-year survival as well and rarely find a 3- or 5-year survival rate of over 15%.

Moreover there is the limitation that the KKN is a young cancer registry, collecting data only since 1st July 2018, but the overall absolute survival rates in our population are consistent with RKI figures for Germany as a whole: The Robert-Koch-Institute (RKI) (22) calculates a 1-, 2- and 3-year survival rate of 39%, 20% and 14% between 2019 and 2020, compared to 39%, 19% and 11% in our study (see Figure S2).

Given that the State of Lower Saxony represents 10% of the German population, and is demographically representative in terms of age, gender (23), and PC incidence (24), this congruence supports the validity of our findings. Finally, while we focus on absolute survival, relative and absolute survival times for PC in Germany differ by only approximately 1% (22). This further underscores the robustness of our results, despite the limitations inherent to registry-based studies.

Conclusions

In conclusion, this study highlights the trend of superiority of FOLFIRINOX in terms of survival for PC patients when ECOG status, and patient preference allow, and supports the use of Gem + Pac over Gem alone, especially in palliative care (UICC stage IV), aligning with S3 guideline recommendations. By incorporating registry data from Germany, our work complements clinical studies, providing a broader perspective on real-world treatment practices and underscoring the value of registry-based research in evaluating guideline effectiveness.

Acknowledgments

The authors would like to thank Eva-Maria Bonin for her support of writing–review & editing, and validation.

Footnote

Reporting Checklist: The authors have completed the RECORD reporting checklist. Available at https://apc.amegroups.com/article/view/10.21037/apc-24-36/rc

Data Sharing Statement: Available at https://apc.amegroups.com/article/view/10.21037/apc-24-36/dss

Peer Review File: Available at https://apc.amegroups.com/article/view/10.21037/apc-24-36/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apc.amegroups.com/article/view/10.21037/apc-24-36/coif). The authors have no conflicts of interest to declare.

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. In accordance with German legislation (§12 Nds. KKRDG, §65c SGB V), the use of cancer registry data for scientific research purposes does not require separate ethical approval, provided that the data are used in pseudonymized form and no personal identifiers are accessible to the researchers. Our study exclusively uses data from the KKN, which are collected on a statutory basis and processed in accordance with strict data protection standards. Importantly, the analysis of pseudonymized registry data does not involve any intervention or influence on patient care, nor does it affect access to treatment or outcomes at the individual level. Thus, there is no ethical risk to participants, and the study complies fully with the Declaration of Helsinki and its subsequent amendments, and applicable national and European data protection regulations. This approach is consistent with established practice in Germany and has been used in comparable peer-reviewed studies based on German cancer registry data.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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