Current practices and challenges in the management of nonmetastatic pancreatic adenocarcinoma: results of an EORTC survey

Abstract

Background

The optimal therapeutic strategy for nonmetastatic pancreatic ductal adenocarcinoma (PDAC) remains controversial. This study sought to provide an overview of contemporary clinical management patterns across Europe.

Materials and methods

A survey was designed by a multidisciplinary team under the aegis of the European Organization of Research and Treatment of Cancer Gastrointestinal Tract Cancer Group, providing insights into initial diagnosis, surgery, and clinical management of patients with resectable, borderline resectable (BR), and locally advanced (LA) PDAC.

Results

Eighty-three practitioners from 16 European countries answered the survey. In cases of resectable PDAC, frontline surgery was the preferred option (74%) followed by neoadjuvant chemotherapy (22%). For BR PDAC, the preferred induction strategy was chemotherapy alone (70%). Radiotherapy (RT) was proposed to be added after chemotherapy in cases of poor response or persistence of vascular contact (37%). For LA PDAC, the panel’s strategies were (i) induction chemotherapy followed by chemoradiotherapy (42%), (ii) chemotherapy alone (35%), and (iii) chemotherapy followed by stereotactic body radiotherapy (23%). In cases of very good response without remaining vascular contact or with a carbohydrate antigen 19-9 (CA19-9) normalization after induction chemotherapy, cancellation of the planned RT, leading to immediate surgical exploration, was proposed in 77% and 42%, respectively.

Conclusion

This European survey highlights the significant heterogeneity in PDAC clinical practices and the frequent reconsideration and adaptation of the initially planned therapeutic strategies according to treatment response, a question not explored in clinical trials. This study demonstrates the urgent need to harmonize practices in Europe.

Highlights

• •Marked heterogeneity in clinical management of nonmetastatic pancreatic adenocarcinoma across Europe.
• •Reconsideration of initially planned therapeutic strategy according to treatment response is a common real-world practice.
• •Despite limited evidence, strategies including radiotherapy remain the preferred option for LA tumors.
• •Efforts to harmonize clinical practices in Europe must be developed.

Introduction

Unlike the majority of other solid tumors, the 5-year overall survival (OS) rate of pancreatic ductal adenocarcinoma (PDAC) has only slightly changed over the last decade due to the difficulty in obtaining an early diagnosis and a particularly high resistance to systemic treatments and radiotherapy (RT).1, 2, 3 Therefore, PDAC remains the cancer with the lowest survival rate in Europe, leading to almost 135 000 deaths per year.⁴ This cancer is projected to become the second leading cause of cancer-related death and is expected to place a substantial and growing burden on European health care systems due to its steadily rising incidence.⁴ Despite the relative stability of the available therapeutic options—the three main pillars remaining surgery, chemotherapy, and RT—the management of nonmetastatic PDAC can be variable among European centers, notably due to lack of high-level evidence, controversies in clinical trial results, and differences in accessibility to the different therapeutic modalities in routine care settings.^5,6 Several European and international consensus guidelines exist for the management of nonmetastatic PDAC; however, it remains unclear to what extent these guidelines are followed in Europe.^7,8 As 5-year OS rates for PDAC vary across European countries, differences in the management and treatment of nonmetastatic disease may contribute to these disparities.9, 10, 11, 12, 13 For instance, in the SUDCAN population-based study, 5-year OS ranged from 6% to 10% across six European countries, highlighting measurable intercountry variability in outcomes.¹⁰ Therefore, we designed a multidisciplinary survey regarding the management of nonmetastatic PDAC across Europe with the endorsement of the European Organization of Research and Treatment of Cancer (EORTC), aiming to obtain a real-world analysis of current clinical practices in Europe.

Materials and methods

In March 2024, a survey was developed by a multidisciplinary team (radiation oncologists [ROs], medical oncologists, and gastroenterologists) under the aegis of the EORTC Gastrointestinal Tract Cancer Group and validated by the Radiation Oncology Science Council. The survey consisted of 85 items on the diagnosis and therapeutic management of nonmetastatic PDAC (Supplementary Data S1, available at https://doi.org/10.1016/j.esmogo.2025.100257). The questionnaire was divided as follows: (i) general information, (ii) diagnosis, (iii) surgery and pathology protocol, (iv) RT protocol, (v) management of resectable PDAC, (vi) management of borderline resectable (BR) PDAC, and (vii) management of locally advanced (LA) PDAC. The Google Form platform was used (Google, Mountain View, CA), and the survey was distributed between March and June 2024 through the EORTC network and several national societies of digestive cancer and radiation oncology (including the French Partenariat de Recherche en Oncologie DIGEstive [PRODIGE] and the Belgian B-ROG/BeSTRO groups), to reach gastroenterologists, medical oncologists, ROs, and digestive surgeons practicing in Europe. Answers were collected, and aggregated results were analyzed by calculating frequencies and percentages using Stata 14 software (Stata Corp LLC, College Station, TX).

Results

General information

A total of 83 practitioners from 16 European countries and 75 different centers answered the survey between 20 March and 30 June 2024. The top-three responding countries were France (N = 40%), Italy (N = 14%), and Belgium (N = 12%). The respondents were mainly medical oncologists and ROs (40% and 28%, respectively) practicing in university hospitals (70%). A majority of participants had a very experienced profile, treating patients with PDAC for >0 years (61%) and holding an MD and a PhD degree (53%). The demographic characteristics of the respondents are detailed in Table 1.

Table 1.

General demographic characteristics of the respondents

Items	N = 83
Age (years), N (%)
<30	1 (1)
30-40	25 (30)
40-50	26 (31)
50-60	26 (31)
>60	5 (6)
Gender, N (%)
Male	56 (68)
Female	27 (32)
Specialty, N (%)
Medical oncologist	33 (40)
Radiation oncologist	23 (28)
Gastroenterologist	15 (18)
Surgeon	12 (14)
Country, N (%)
France	33 (40)
Italy	12 (14)
Belgium	10 (12)
Spain	7 (8)
Germany	6 (7)
Portugal	2 (2)
United Kingdom	2 (2)
Lithuania	2 (2)
Switzerland	2 (2)
Albania	1 (1)
Czech Republic	1 (1)
Luxembourg	1 (1)
Slovenia	1 (1)
Netherlands	1 (1)
Serbia	1 (1)
Türkiye	1 (1)
Type of center, N (%)
Public–University Center	58 (70)
Comprehensive Cancer Center	10 (12)
Private	9 (11)
Public–Non University Center	6 (7)
Years since the obtention of MD degree
<5	6 (7)
5-10	13 (16)
10-20	30 (36)
>20	34 (41)
Highest academic qualification
MD	31 (37)
MD, MSc	8 (10)
MD, PhD	44 (53)
Experience in treating PDAC, N (%)
<5 years	8 (10)
5-10 years	24 (29)
10-20 years	22 (26)
>20 years	29 (35)
Number of patients with PDAC treated per year, N (%)
<25	30 (36)
25-50	34 (41)
50-100	13 (16)
>100	6 (7)

MD, medical degree; MSc, master of science; PDAC, pancreatic ductal adenocarcinoma; PhD, doctor of philosophy.

Diagnosis

The answers received regarding the initial assessment of nonmetastatic PDAC are summarized in Table 2. Briefly, physical examination, standard biological tests with carbohydrate antigen 19-9 (CA19.9), and abdominopelvic computed tomography (CT) scan (with triple-phase contrast, if feasible) were systematically carried out, while thoracic CT scan was systematic for 83%, abdominal magnetic resonance imaging (MRI) for 49%, [¹⁸F]2-fluoro-2-deoxy-D-glucose positron emission tomography (PET)-CT for 16%, explorative laparoscopy for 6%, and nutritional evaluation for 72% of the respondents. The initial nutritional evaluation consisted of evaluating weight at diagnosis (89%), evaluation by a dietitian (62%), (pre-) albumin dosage (58%), evaluation by a nutritionist (29%), or the Visual Analog Scale of food intake (18%). New diagnoses of nonmetastatic PDAC were systematically reviewed at a dedicated multidisciplinary oncology consultation (MOC) for 93% of the panel.

Table 2.

Detailed results of the initial assessment and procedures systematically carried out in Europe for nonmetastatic pancreatic adenocarcinoma (n = 83)

Assessment/procedure	Systematically carried out (%)
Physical examination	95
Standard laboratory tests (including CA19.9)	99
Abdominopelvic CT scan (with triple-phase contrast if feasible)	99
Thoracic CT scan	83
Abdominal MRI	49
FDG-PET	16
EUS	59
ERCP	14.5
Biopsy/cytology	82
Exploratory laparoscopy	6
Nutritional evaluation (any modality)	72
- Weight assessment at diagnosis	89
- Dietitian evaluation	61.5
- (Pre-)albumin dosage	58
- Nutritionist evaluation	29
- Ingesta Visual Analog Scale	18
MOC review	93

CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; FDG-PET, [¹⁸F]2-fluoro-2-deoxy-D-glucose-positron emission tomography; MOC, multidisciplinary oncology consultation; MRI, magnetic resonance imaging.

Surgery and pathology protocol

For 61% of the respondents, surgery was centralized in high-volume centers (≥20 resections carried out annually). The classification of resectability used was mainly the definition of the National Comprehensive Cancer Network (NCCN;⁸ 83%). The Dutch classification of resectability¹⁴ was used in 11.5%, and the remaining 5.5% of the respondents used diverse in-house definitions. No clear consensus was reached for the definition of free/involved margins (R0/R1), as 24% of the panel routinely applied an R0 > 0 mm definition, 45% R0 ≥ 1 mm, and 31% used an R0 > 1 mm definition. The type of surgical margins considered for the definition of R0/R1 margins was also highly variable. A standardized pathological examination protocol was used in most cases (62%), but was from various origins (ICCR guidelines, Royal College of Pathology, College of American Pathology [CAP], or national/in-house pathology guidelines). Similarly, when a pathological classification was used to assess the response to neoadjuvant treatment, various scoring systems were reported, including the CAP Modified Ryan Scheme (0-3), the Evans grading system (I-IV), the MD Anderson classification (0-2), as well as ‘in-house’ systems. Vascular reconstructions, when indicated, were carried out in most centers (67.5%) and consisted mainly of venous reconstructions [portal vein/confluence and superior mesenteric vein (99% and 75%, respectively)] while arterial reconstructions were offered by a quarter of the panel [common hepatic artery (29%), superior mesenteric artery (27%), and coeliac trunk (25%)].

RT protocol

Among the panel of respondents, 37 of them were aware of the details of their in-house RT protocol. RT facilities routinely available for the treatment of PDAC were as follows: (i) conventional Linac—82%, (ii) stereotactic body radiotherapy (SBRT) dedicated Linac—77%, (iii) CyberKnife® (Accuray Inc., Sunnyvale, CA)—25.5%, (iv) magnetic resonance Linac—23%, and (v) particle therapy—4%. Recent technological advancements for mitigating respiratory movements were commonly used for treating pancreatic cancer, such as 4D-CT (78%), gating (73%), breath-hold (70%), abdominal compression devices (54%), tracking (54%), cine-MRI (32%), and midpositioning (32%). Patient positioning was mainly supine with arms above the head. Diverse prophylactic drugs or regimens were frequently applied during RT treatments, either in cases of SBRT or chemoradiotherapy (CRT), and were as follows: anti-emetics (70%), proton pump inhibitor (65%), adapted diet (23%), intestinal gas reducer (14%), and antispasmodic (11.5%). In cases of CRT, the concomitant chemotherapy regimen was in order of preference: capecitabine (67%), full-dose gemcitabine according to the PREOPANC trial¹⁴ (33%), 5-FU (24%), gemcitabine (6%), 5-FU/folinic acid plus cisplatin (3%), and 5-FU/folinic acid plus irinotecan (3%).

Management of upfront resectable PDAC

In cases of newly diagnosed upfront resectable PDAC (as defined by the NCCN resectability criteria),⁸ the treatment sequence most frequently offered by the panel was surgery first (74%), while 23% recommended neoadjuvant chemotherapy, and 3% induction chemotherapy followed by CRT. The choice of initial therapeutic strategy for upfront resectable PDAC across professional backgrounds and European countries represented in this survey (France, Italy, Belgium, Spain, Germany, and other countries) is detailed in Supplementary Figures S1 and S2 (available at https://doi.org/10.1016/j.esmogo.2026.100372) and did not differ significantly (P = 0.412 and P = 0.58, respectively). When asked which criteria were used to select patients with resectable PDAC for a neoadjuvant treatment strategy, the majority of respondents indicated that they offered neoadjuvant therapy when at least one NCCN-defined ‘high-risk criterion’ (i.e. equivocal/indeterminate imaging findings, markedly elevated CA19.9, large primary tumor, large regional lymph nodes, excessive weight loss, and extreme pain)⁸ was present (87%). In contrast, 10% of respondents reported never using neoadjuvant treatment in this setting. As the NCCN definition of ‘high-risk criteria’ does not specify an exact cut-off for elevated levels of CA19.9 in the absence of cholestasis, respondents reported applying the following thresholds when considering induction therapy: 500 kU/L (60%), 200 kU/L (26%), and 1000 kU/L (12%). For fit patients receiving neoadjuvant chemotherapy, modified FOLFIRINOX (mFFX, without 5-FU bolus) was the preferred regimen (58.5%), followed by full-dose FFX (38.5%), and gemcitabine/nab-paclitaxel (Gem/NbP, 3%). When used, neoadjuvant chemotherapy was most commonly administered for 4-6 cycles. The main results are summarized in Table 3.

Table 3.

Detailed results of the responses obtained regarding the management of upfront resectable pancreatic cancer

Items for upfront resectable PDAC	Percentage (%) N = 83
Primary treatment sequence
Surgery first	74
Neoadjuvant chemotherapy	23
Induction chemotherapy + CRT	3
Criteria for selecting neoadjuvant CT
Presence of ≥1 NCCN high-risk criteria	87
Never use neoadjuvant therapy	10
Always carried out	1
Other criteria used	2
CA19.9 cut-offs triggering induction CT
500 kU/L	60
200 kU/L	26
1000 kU/L	12
Other	2
Preferred neoadjuvant chemotherapy regimen (fit patients)
Modified FOLFIRINOX (mFFX, no 5-FU bolus)	58.5
Full-dose FOLFIRINOX (FFX)	38.5
Gemcitabine/nab-paclitaxel (Gem/NbP)	3
If neoadjuvant chemotherapy is used, preferred number of cycles
4-6	61.5
6-8	9.5
>8	3.5
NA	25.5

CA19.9, carbohydrate antigen 19-9; CRT, chemoradiotherapy; CT, chemotherapy; NA, not applicable; NCCN, National Comprehensive Network; PDAC, pancreatic adenocarcinoma.

Management of BR PDAC

Regarding the management of BR PDAC (defined according to the NCCN resectability criteria),⁸ the treatment sequence most commonly offered by the panel was neoadjuvant chemotherapy (69%), while 26% recommended neoadjuvant chemotherapy followed by RT (14% with SBRT and 12% with CRT), and 5% surgery first. Although no difference was observed in the choice of the preferred treatment management of BR PDAC across European countries, statistically significant differences emerged between medical specialties (P = 0.556 and P = 0.003, respectively). ROs showed a marked preference for neoadjuvant approaches integrating RT (either CRT or SBRT), whereas medical oncologists and gastroenterologists favored induction chemotherapy alone (Supplementary Figures S3 and S4, available at https://doi.org/10.1016/j.esmogo.2026.100372). Notably, 33% of respondents distinguished different subtypes of BR PDAC based on the type of vascular involvement (arterial versus venous), leading them to select different therapeutic strategies accordingly. Furthermore, 18% of the panel no longer considered a curative-intent strategy in the presence of elevated CA19.9 at diagnosis, with a median threshold of 500 kU/L.

For 61% of respondents, the ‘surgery first’ approach was never applicable in BR PDAC, while 39% still considered it under specific conditions: patients unfit for multiagent chemotherapy (56.5%), patients with venous-only BR disease (41%), elderly patients (36%), CA19.9 < 200 kU/L (33%), cN0 status (15.5%), biliary obstruction (15.5%), or PDAC arising from a degenerated intraductal papillary mucinous neoplasm (10%). When a neoadjuvant approach was selected for BR PDAC, the decision criteria were as follows: systematically for fit patients (83%), cN+ disease (29%), elevated CA19.9 (28%; median cut-off: 500 kU/L), arterial BR disease only (21.5%), and large primary tumor size (15.5%). Modified FFX without 5-FU bolus was the first choice of neoadjuvant chemotherapy for fit patients (54%), followed by full-dose FFX (41%), and various gemcitabine-based regimens (5%). When administered, neoadjuvant chemotherapy was typically given for 3-4 months (35% and 30% of respondents, respectively), provided no limiting toxicity occurred. Restaging after induction therapy was reported to be carried out both midway and at the end of the neoadjuvant sequence for 78% of the panel and only at the end of the neoadjuvant sequence for 22%.

Moreover, an adaptive strategy, modifying the initial therapeutic plan by adding radiotherapy after induction chemotherapy, was adopted by 37% of respondents, primarily in the context of poor response or persistent vascular contact (mainly arterial). When RT was incorporated into the therapeutic sequence for BR PDAC, conventional CRT was used by 47%, followed by ‘high-dose’ SBRT (30%; defined as a biologically effective dose [BED₁₀] > 60 Gy), ‘low-dose’ SBRT (17%, defined as a BED₁₀ ≤ 60 Gy), and hypofractionated CRT according to the PREOPANC regimen¹⁴ (8.5%). RT was administered at the end of the induction chemotherapy, except in centers following the PREOPANC or STEREOPAC trial protocols, where RT was delivered between induction cycles.^14,15 After RT, exploratory surgery was planned after a minimum interval of 4 weeks (range 2-6) and a maximum of 8 weeks (range 4-10). The detailed results are summarized in Table 4.

Table 4.

Detailed results of the responses obtained regarding the management of borderline resectable pancreatic cancer

Items for borderline resectable PDAC	Percentage
Primary treatment sequence
Neoadjuvant chemotherapy	69
Neoadjuvant chemotherapy + CRT	12
Neoadjuvant chemotherapy + SBRT	14
Surgery first	5
Surgery-first applicability for BR PDAC
Never applicable for BR PDAC	61
Considered if:
• Patient unfit for multiagent chemo	56.5
• BR with venous contact only	41
• Elderly patients	36
• CA19.9 < 200 kU/L	33
• cN0	15.5
• Biliary obstruction	15.5
• Degenerated PDAC from IPMN	10
Criteria for applying a neoadjuvant strategy
Systematically for fit patients	83
cN+	29
Elevated CA19.9	28
BR with arterial contact	21.5
Large primary tumor	15.5
Preferred neoadjuvant CT regimen (fit patients)
Modified FOLFIRINOX (no 5-FU bolus)	54
Full-dose FOLFIRINOX	41
Gemcitabine-based regimens	5
Preferred duration of neoadjuvant CT
1 month	1
2 months	13.5
3 months	35
4 months	30
6 months	18
Other	2.5
Restaging timing
Intermediate AND at the end of the neoadjuvant sequence	78
Only at the end of the neoadjuvant sequence	22
Type of RT used
Conventional CRT	47
Hypofractionated CRT (from PREOPAN10)9	8.5
Low-dose SBRT (BED10 ≤ 60 Gy)	17
High-dose SBRT (BED10 > 60 Gy)	30
Minimal allowed timing of exploratory surgery after RT (weeks)
1	2.5
2	2.5
3	12
4	42
6	8.5
Not applicable	32.5
Maximal allowed timing of exploratory surgery after RT (weeks)
4	1
5	2.5
6	11
7	2.5
8	36
9	1
10	13.5
Not applicable	32.5

BED10, biologically effective dose, alpha/beta=10; BR, borderline resectable; CA19.9, carbohydrate antigen 19-9; cN+, clinically involved lymph node; CRT, chemoradiotherapy; CT, chemotherapy; IPMN, intraductal papillary mucinous neoplasm; PDAC, pancreatic adenocarcinoma; RT, radiotherapy; SBRT, stereotactic body radiotherapy.

Management of LA PDAC

Regarding the management of LA PDAC (as defined by the NCCN resectability criteria),⁸ the treatment sequence most often offered by the panel was highly debated: 42% opted for ‘induction’ chemotherapy followed by CRT, 35% for ‘induction’ chemotherapy only, and 23% for ‘induction’ chemotherapy followed by SBRT. Once again, treatment strategies did not differ significantly across European countries (P = 0.78). In contrast, a significant association emerged when stratifying responses by medical specialty (P = 0.014). Surgeons were more likely to report using ‘induction’ chemotherapy alone, whereas ROs tended to favor induction regimens incorporating RT, particularly SBRT. Medical oncologists and gastroenterologists demonstrated more heterogeneous patterns, without strong over- or underrepresentation of any specific strategy (Supplementary Figures S5 and S6, available at https://doi.org/10.1016/j.esmogo.2026.100372). For fit patients, the preferred chemotherapy regimen was full-dose FFX (50.5%), followed by mFFX (42%), and gemcitabine-based regimens (6%). In the absence of treatment-limiting toxicity, chemotherapy was typically administered for 4-6 months (reported by 30% and 43% of respondents, respectively). The most frequently proposed RT approaches were conventional CRT (63.5%), followed by ‘high-dose’ SBRT (28%), then ‘low-dose’ SBRT (8.5%). RT was delivered at the end of chemotherapy for 91% of the panel. For patients with LA tumors not considered ‘never resectable’, and in the absence of disease progression at restaging after the selected therapeutic strategy (chemotherapy ± RT), surgical exploration was systematically proposed by 36% of the panel. Conversely, 16% never considered surgical exploration in this context, while 48% reported considering it selectively depending on the case. The criteria used for this selective decision making varied widely across clinicians. The detailed results are summarized in Table 5.

Table 5.

Detailed results of the responses obtained regarding the management of LA pancreatic cancer

Items for LA PDAC	Percentage (n = 83)
Primary treatment sequence
Induction CT only	35
Induction CT + CRT	42
Induction CT + SBRT	23
Preferred CT regimen (fit patients)
Full-dose FOLFIRINOX	50.5
(FFX) mFFX: no FU bolus	31
mFFX: dose reduction of irinotecan	11
Gem/NbP	5
Other Gem-based regimen	2.5
Preferred duration of CT (if tolerated)
- 2 months	2.5
- 3 months	14
- 4 months	30
- 6 months	43
- 8 months	7
- Other	3.5
RT as part of the initial treatment strategy
Never	12
Yes, always	31
Yes, sometimes (n = 47):	57
- For local control in case of non-M+ progression after CT	18
- If intolerance to CT	4
- Non-M+ tumor not deemed resectable after CT	38
- Other /no criteria mentioned	40
RT strategies offered
Conventional CRT	63.5
High-dose SBRT (BED10 > 60 Gy)	28
Low-dose SBRT (BED10 ≤ 60 Gy)	8.5
Timing of RT if used
At the end of CT	76
‘In sandwich’ in between CT	6
Before CT	1
NA	17
Surgical exploration offered for LA tumors (not deemed “never resectable”) after induction
Systematically	36
Never	16
Sometimes (various criteria)	48
Minimal allowed timing of exploratory surgery after RT (weeks)
1-2	1
3	6
4-5	47
6	24
7-8	5
NA	17
Maximal allowed timing of exploratory surgery after RT (weeks)
4-5	3.5
6	8.5
7	3.5
8	38.5
9-10	21
NA	25

BED10, biologically effective dose, alpha/beta=10; CRT, chemoradiotherapy; CT, chemotherapy; Gem/NbP, gemcitabine/nab-paclitaxel; LA, locally advanced; m(FFX), (modified) FOLFIRINOX; NA, not applicable; PDAC, pancreatic adenocarcinoma; RT, radiotherapy; SBRT, stereotactic body radiotherapy.

Reconsideration and modification of the initial therapeutic strategy were frequent. Cancellation of RT after chemotherapy was considered in cases of (i) very good radiological response to chemotherapy with downsizing and no remaining vascular contact (77%), (ii) very good metabolic response to chemotherapy with complete response on PET-CT (62%), and (iii) very good biological response to chemotherapy with normalization of CA19.9 (42%). Tumor size alone was not considered a major criterion to alter the therapeutic plan for LA PDAC, except for 6% of the respondents, who applied varying size thresholds.

Discussion

We present the results of a survey, endorsed by the EORTC, assessing the management of nonmetastatic PDAC with a particular focus on neoadjuvant strategies, providing insights into the real-world clinical practices across Europe. Despite the fact that the participating physicians were, for the most part, highly experienced in treating patients with PDAC, substantial heterogeneity was observed at each level of the nonmetastatic PDAC management steps throughout the questionnaire.

Concerning initial staging, although chest CT is mandatory according to current guidelines to adequately exclude the existence of lung metastases,^7,8 only 83% of respondents reported using it systematically. Conversely, despite being less accessible in routine practice, abdominal MRI was more widely used than expected, with half of the panel performing it systematically at diagnosis. While abdominal MRI is mandatory only in specific situations in international guidelines, it may offer a substantial advantage in the management of PDAC, particularly before surgery, to better exclude the existence of small liver metastases.^7,8,16 Nutritional evaluation, recently recognized as a key factor influencing outcomes and surgery, now appears to be considered an essential component of routine practice, although there remains room for improvement, as it is not carried out by nearly 30% of respondents.^17,18 In contrast, although strongly advocated by several authors, staging abdominal laparoscopy is clearly not integrated into daily practice in Europe.^7,8,19

While newly diagnosed nonmetastatic cases are discussed in a dedicated MOC for nearly all respondents, which is crucial for accurate staging, the highly specialized surgery required for PDAC was not typically centralized in experienced high-volume centers. Exceptions were Belgium, the Netherlands, and Portugal, where centralization is mandatory.²⁰ This lack of centralization led to clear differences in the vascular reconstructions proposed for patients with nonmetastatic PDAC across Europe and may contribute to inequalities in surgery-related complications and mortality. Several controversies persist regarding the exact definition of R0-margins in PDAC, as well as standardized protocols for pathological assessment and evaluation of response to neoadjuvant treatment. This variability was reflected in the answers to this survey. Currently, almost every center applies a different R0 definition, making it difficult to compare clinical studies that use surgical margin status as an endpoint. Nevertheless, at least 76% of respondents agreed on the 1-mm criterion, although uncertainty remained among clinicians regarding whether it should be defined as ≥1 mm or >1 mm. The definition of resectability proposed by the NCCN appears to achieve a clearer consensus overall; however, 17% of the panel still reported using an alternative definition (either the Dutch criteria or an institutional in-house definition), which further complicates the comparison of clinical outcomes across studies.^8,14

Among the nonmetastatic subgroups, it is not surprising that the upfront resectable group showed the greatest homogeneity in management strategies, although there remains room for improvement. Nevertheless, the existence of various and not well-defined high-risk criteria in the NCCN guidelines allows for substantial variability in interpretation and clinical decision making.⁸ These criteria encourage the use of neoadjuvant treatment in the presence of one or more risk factors, but without precise definitions. This may partly explain the more cautious adoption of neoadjuvant strategies in upfront resectable PDAC in Europe. In many centers, there is still a strong tendency to prioritize upfront surgical resection. This approach likely reflects concerns about potential disease progression during preoperative therapy, as well as variability in patient selection. The BR group displays a particularly high level of management complexity, owing to controversies in clinical trial results, the lack of high-level evidence, and its intermediate position regarding the surgical feasibility.^5,6,8 Beyond the NCCN definition of BR resectability, many clinical and biological factors are also taken into account in daily practice (e.g. the ABC classification: anatomical, biological, conditional), leading clinicians to modulate the treatment strategy accordingly.²¹ Reconsideration and modification of the initially planned therapeutic strategy according to disease response to chemotherapy were very common in the management of both BR and LA PDAC, despite such adaptive approaches being either prohibited or only minimally allowed within clinical trial protocols.

Significant differences in preferred therapeutic strategies were observed across medical specialties, particularly regarding the use of RT. Overall, a wide diversity of practices emerged in the management of nonmetastatic PDAC, with RT remaining frequently implemented in daily clinical practice. Notably, despite recent European Society for Medical Oncology guidelines recommending chemotherapy alone as the standard of care for LA PDAC, a combined ‘chemotherapy + RT’ strategy was still reported as the preferred initial option by 65% of the panel.^8,22 This apparent discrepancy may be explained by the limitations of the available evidence. Indeed, randomized controlled trials (RCTs) evaluating conventional CRT or ‘low-dose’ SBRT in both BR and LA PDAC, including LAP-07, CONKO-007, PANDAS/PRODIGE 44, and Alliance A021501, have been negative and have failed to demonstrate a survival benefit.23, 24, 25, 26 However, RT continues to be widely used in clinical practice, likely reflecting its perceived benefits beyond OS. These include improved local disease control, symptom palliation (particularly pain), and a potential increase in (R0-) resection rates in selected patients. Given that a substantial proportion of patients experience significant morbidity or death related to uncontrolled local progression, these considerations may justify the continued integration of RT into routine treatment strategies.²²

To date, the only phase III trial reporting a positive survival signal in favor of RT is PREOPANC-1, in which hypofractionated CRT (36 Gy in 15 fractions) combined with full-dose gemcitabine improved long-term survival compared with upfront surgery in a mixed population of resectable and BR PDAC.^10,27 However, this regimen remains infrequently used in current European practice, as clinicians tend to favor modern multiagent chemotherapy over the older gemcitabine standard, a preference further reinforced by the results of the PREOPANC-2 trial, in which FFX did not demonstrate superiority over hypofractionated CRT.²⁸ Finally, the landscape of RT is evolving, with several ongoing RCTs assessing intensified RT approaches, particularly high-dose SBRT (notably STEREOPAC [NCT05083247] for BR PDAC, and TORPEDO [NCT06691425], NRG-GI011 LAP100 [NCT06958328], and LAPSTAR [NCT06272162] for LA PDAC).^15,29, 30, 31 In parallel, as reflected in this survey, the use of ‘high-dose’ SBRT is steadily increasing in clinical practice, driven by the growing availability of advanced RT technologies (MR-Linac, real-time tracking, breath-hold, etc) which may enhance treatment precision and therapeutic ratio.^5,15,29, 30, 31, 32, 33

The limitations of the present survey include that the overall landscape of current clinical practice may not be fully captured, as participation was voluntary and dissemination relied primarily on EORTC-affiliated networks. Consequently, the representation of participating centers may not perfectly reflect European practice, with some countries being underrepresented or not represented at all. In addition, the relatively limited number of respondents, partly explained by the targeted inclusion of PDAC specialists and the length of the questionnaire, may have introduced a selection bias toward more specialized or academically oriented centers. It should also be noted that the survey results were collected before the publication of the final results of the PRODIGE PANDAS and the PACT-21 CASSANDRA trials, and therefore may not fully reflect current practices regarding CRT for BR PDAC or the use of the PAXG regimen (cisplatin, nab-paclitaxel, capecitabine, and gemcitabine).^26,34 Finally, surgeons were underrepresented in the panel, and no responses from radiologists or pathologists were included.

Conclusion

Multiple uncertainties persist regarding the optimal management of patients with nonmetastatic PDAC, particularly concerning the frequent reconsideration of the initially planned therapeutic strategy based on treatment response to chemotherapy. This adaptive decision making, commonly applied in real-world practice but largely absent from clinical trial designs, represents a major gap between evidence-based recommendations and daily clinical management. The results of this European survey highlight substantial heterogeneity across centers, specialties, and countries, reflecting the absence of clear, unified recommendations for several critical steps of the therapeutic pathway. This study emphasizes the importance of collaborative efforts to harmonize and standardize clinical practices in Europe and provides a valuable foundation for the development and design of future European clinical trials.

Declaration of generative AI and AI-Assisted technologies in the writing process

Following the reviewers’ comments, the authors used Copilot to verify and identify the remaining grammatical errors within the manuscript. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.