Timing of Initiation of Palliative Chemotherapy in Asymptomatic Patients with Metastatic Pancreatic Cancer: An International Expert Survey and Case-Vignette Study

Simple Summary The use of imaging, in general and during follow-up after resection of pancreatic cancer, is increasing. Consequently, the number of asymptomatic patients diagnosed with metastatic pancreatic cancer (mPDAC), both at initial diagnosis and during the diagnosis of recurrent disease, is increasing. In these patients, palliative systemic therapy is the only (tumor-directed) therapy and, hence, is often immediately initiated. However, delaying therapy until symptoms occur may preserve quality of life and avoid therapy-related toxicity, but the impact on survival of this approach is unknown. Using an online survey sent to all first and last authors of published trials on mPDAC and to medical oncologists of the Dutch Pancreatic Cancer group, this study aimed to gain insight into the current perspectives and clinical decision-making of experts. Overall, 78 of 291 (27%) medical oncologists from 15 countries responded. Two-thirds of respondents (63%) preferred an immediate initiation of chemotherapy following diagnosis. In 3/9 case-vignettes, delayed treatment was favored in specific clinical contexts (i.e., patient with only one small lung metastasis, significant comorbidities, and higher age). Respondents from the Netherlands, as well as medical oncologists with fewer years of experience, more often favored delayed treatment. Although the response rate was limited, in this increasing group of asymptomatic patients with mPDAC, immediate treatment is most often preferred, although in specific clinical contexts (i.e., limited metastatic disease, more comorbidities, and higher age), delaying treatment until symptoms occur is considered.Abstract Background: The use of imaging, in general, and during follow-up after resection of pancreatic cancer, is increasing. Consequently, the number of asymptomatic patients diagnosed with metastatic pancreatic cancer (mPDAC) is increasing. In these patients, palliative systemic therapy is the only tumor-directed treatment option; hence, it is often immediately initiated. However, delaying therapy in asymptomatic palliative patients may preserve quality of life and avoid therapy-related toxicity, but the impact on survival is unknown. This study aimed to gain insight into the current perspectives and clinical decision=making of experts regarding the timing of treatment initiation of patients with asymptomatic mPDAC. Methods: An online survey (13 questions, 9 case-vignettes) was sent to all first and last authors of published clinical trials on mPDAC over the past 10 years and medical oncologists of the Dutch Pancreatic Cancer Group. Inter-rater variability was determined using the Kappa Light test. Differences in the preferred timing of treatment initiation among countries, continents, and years of experience were analyzed using Fisher's exact test. Results: Overall, 78 of 291 (27%) medical oncologists from 15 countries responded (62% from Europe, 23% from North America, and 15% from Asia-Pacific). The majority of respondents (63%) preferred the immediate initiation of chemotherapy following diagnosis. In 3/9 case-vignettes, delayed treatment was favored in specific clinical contexts (i.e., patient with only one small lung metastasis, significant comorbidities, and higher age). A significant degree of inter-rater variability was present within 7/9 case-vignettes. The recommended timing of treatment initiation differed between continents for 2/9 case-vignettes (22%), in 7/9 (77.9%) comparing the Netherlands with other countries, and based on years of experience for 5/9 (56%). Conclusions: Although the response rate was limited, in asymptomatic patients with mPDAC, immediate treatment is most often preferred. Delaying treatment until symptoms occur is considered in patients with limited metastatic disease, more comorbidities, and higher age.