Neoadjuvant therapy (NT) has increasingly been utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). It is the recommended approach for borderline resectable (BR) and locally advanced (LA) cancers and an increasingly utilized option for potentially resectable (PR) disease. Despite its increased use, little research has focused on patient-centered metrics among patients undergoing NT, including patient experiences, preferences, and recommendations. A better understanding of all aspects of the patient experience during NT may identify opportunities to design interventions aimed at improving quality of life; it may also facilitate the completion of NT and receipt of surgery, ultimately optimizing long-term outcomes.

To understand the experience of patients initiating and receiving NT to identify opportunities to improve neoadjuvant cancer care delivery.

Semi-structured interviews of patients with localized PDAC during NT were conducted to explore their experience initiating and receiving NT. Interviews took place between August 2020 and October 2021. Due to the descriptive nature of the research, questions were open ended. Interviews were conducted over the phone, audio recorded and then transcribed. All interviews were coded by two independent researchers using NVivo 12, iteratively identifying themes until thematic saturation was achieved. An integrative approach to qualitative analysis was used, utilizing both inductive and deductive methods.

A total of 12 patients with localized PDAC were interviewed. Patients with BR (n = 7), PR (n = 2), and LA (n = 3) cancers participated in the study. All patients indicated that choosing NT was the doctor’s recommendation, while most reported not being familiar with the concept of NT (n = 11) and that NT was presented as the only option (n = 8). Five themes describing the patient experience emerged: physical symptoms, emotional symptoms, coping mechanisms, access to care, and life factors. The most commonly cited recommendation for improving the experience of NT was improved education before and during NT (n = 7). Patients highlighted the need for more information on the rationale behind choosing NT prior to surgery, the anticipated surgery and its likelihood of surgery occurring after NT, as well as general information prior to starting NT treatment. The need for seeing different members of the healthcare team, including ancillary services was also frequently cited as a recommendation for improving the experience of NT (n = 5).

This study provides a framework to allow for a better understanding of the PDAC patient experience during NT and highlights opportunities to improve quality and quantity of life outcomes.

The delivery of chemotherapy and/or radiation therapy prior to surgery, known as neoadjuvant therapy (NT), is increasingly utilized for patients with pancreatic ductal adenocarcinoma (PDAC)[1,2]. Since a significant proportion of patients are unable to receive all intended adjuvant therapies following major pancreatectomy, NT ensures the receipt of some systemic therapy and leads to improved rates of multimodality therapy. NT also improves margin-negative resection rates, enhances patient selection by ensuring the absence of rapid tumor progression prior to surgery, enables an in vivo test of the efficacy of chemotherapy, and based on emerging evidence from randomized controlled trials, may lead to improved overall survival[3-7]. Based on these advantages, NT is now the recommended approach for borderline resectable (BR) and locally advanced (LA) cancers and an increasingly utilized option for potentially resectable (PR) disease according to national guidelines[3,8,9].

Despite its increasing use in PDAC and other cancer types[2], little is known about the patient experience during NT. Indeed, the neoadjuvant time period might be particularly distressing for patients who must cope with not only the toxicity of treatment, but also side effects from the tumor itself which remains in situ. Furthermore, little is known about the psychosocial impact of NT particularly given many patients’ inherent preference for “just getting the cancer out,” as well as the uncertainty of future surgery[10]. A recent systematic review found scarce data on quality of life (QOL) during NT for PDAC and no existing literature on other aspects of the patient experience[11]. In contrast to immediate surgery, NT is also inherently multi-disciplinary in nature. As such, there may be barriers to effective care initiation and coordination that impede the completion of all scheduled therapy and the receipt of surgical resection[12].

Therefore, the purpose of this qualitative study was to characterize the patient experience during NT for PDAC. Specifically, we sought to understand patient treatment preferences, information needs, the physical and psychosocial impact of treatment, and barriers to successful initiation and delivery of NT. A better understanding of all aspects of the patient experience during NT may identify opportunities to design interventions aimed at improving QOL during NT, facilitating completion of NT and receipt of surgery, and ultimately optimizing the long-term outcomes of patients with PDAC.

Pancreatic ductal adenocarcinoma is a highly aggressive malignancy, often thought of as a systemic disease at the time of diagnosis, that requires multimodal therapy with a combination of surgery and chemotherapy in order to achieve meaningful long-term survival[14-17]. NT is being increasingly utilized in patients with localized PDAC[1,3,18]. Previous research on NT for PDAC has focused on its safety, efficacy, and cost-effectiveness with little data on patient-centered preferences or experiences during NT. In this qualitative study of patients actively receiving NT for PDAC, we found several important observations. First, patients are generally unfamiliar with the concept of NT prior to meeting with an oncologist. While many have an inherent preference for upfront surgery, most understand their providers’ recommendation for NT as an attempt to improve resectability (or likelihood of achieving margin-negative resection). Second, patients have unique experiences and care needs during NT that providers should be aware of in order to optimize patient-centered outcomes. A patient-centered approach that supports physical and emotional symptoms and recognizes the importance of life integration is required. Third, specific recommendations for improving the experience of NT prior to surgery were identified.

Interestingly, although patients in our study were actively receiving NT, most were relatively unfamiliar with the concept of NT. All patients expressed that NT was the recommendation of their doctor. While a few patients expressed their desire for a surgery-first approach or to avoid chemotherapy altogether, nevertheless, all patients eventually came to understand and agree with the rationale for NT. This may highlight a disconnect between patients and providers in that systemic chemotherapy is part of the treatment of all patients with pancreatic cancer as even patients with localized cancers who have undergone resection are likely to experience disease recurrence[19,20]. Similar results were found in patients with breast cancer. A study in women with breast cancer who underwent NT found a majority of women understood that chemotherapy was given prior to surgery in order to shrink the tumor but did not grasp the concept that chemotherapy is utilized to treat systemic disease beyond simply local tumor control[21].

Missing from prior studies has been an evaluation of patient-centered preferences and outcomes regarding the use of NT for PDAC. Cancer-related treatment decisions are complex and require consideration of multiple factors; such decisions are often made in the context of shared decision making (SDM), a model in which informed and engaged patients make health-care decisions in conjunction with their providers[22]. The degree to which patients are involved in the SDM process of choosing NT or immediate surgery is unclear. Most patients with cancer desire an active role in making decisions about their care[23] and such patient-centered decision making has been shown to improve patients’ understanding of their treatment options, satisfaction with their health care, and overall quality of life (QOL)[24-26]. Previous research in breast and rectal cancer suggest patient-centered approaches to SDM regarding NT are lacking in clinical practice[27-29]. Indeed, SDM is under-utilized by surgeons in general[30]. Additionally, it is well known that strong emotions and fears may influence treatment decision making[31]. Specifically, emotions may cause behavior or decisions to diverge from more rational or practical decision making consistent with one’s values[32]. For example, patients state their desire to “just get the cancer out” even if this emotional response does not align with one’s values, priorities, or optimal treatment strategy. We found most patients believed NT was their only treatment option moving forward. This is not surprising as a majority of the patients in our study had either BR or LA disease which is currently the preferred treatment strategy based on recent randomized controlled trials[33,34]. Another study has found that most patients believed there was no other treatment option and thus accepted NT[21]. Understanding patient preferences, values, and expectations regarding NT will improve SDM which will lead to not only delivering patient-centered care but also the opportunity to overcome barriers to patient acceptance of NT.

While not previously studied in PDAC, in practice, multiple barriers to the use of NT are often expressed by patients. For example, some patients may have financial concerns secondary to missing work by “delaying” surgery. Others worry about arranging and/or affording transportation for NT due to long travel distances. Additionally, in our study, most, if not all patients, experienced physical and emotional symptoms during NT. Furthermore, the development of toxicities during the course of NT may prove to be a potential barrier that may worsen a patient’s ability to subsequently undergo an operation. A meta-analysis of 38 studies of which 1738 patients received NT found approximately 64% of patients experienced at least grade III toxicity[35]. In fact, this number may be magnified at community hospitals which may not have the same resources as tertiary referral centers to manage toxicities and progress patients through therapy[36-38].

We found that patients with PDAC receiving NT must balance their cancer treatment with other aspects of their lives such as family responsibilities and work in addition to coping with the physical and emotional symptoms that accompany their new diagnosis and treatment (Figure 1). These findings are similar to a previous qualitative study of patients with breast cancer receiving NT. Beaver et al[21] reported five themes among women receiving NT: Coping with the rapid transition from “well” to “ill”, information needs and decision making, needing support and empathy, impact on family, and creating a new “normal”. These findings suggest similar experiences among patients receiving chemotherapy prior to surgery regardless of cancer type. While patients with PDAC certainly have unique challenges such as biliary obstruction, malnutrition, gastric outlet obstruction, as well as cancer-related pain, additional research is needed on supporting the general care needs directly influenced by the neoadjuvant aspects of treatment.

The findings from our study provide a framework to allow for a better understanding of the patient experience during NT and highlight opportunities for inter-disciplinary interventions to improve patient-centered outcomes of those with PDAC. Indeed, many patients who receive NT fail to either complete NT or to undergo subsequent pancreatectomy with common reasons including disease progression or worsening performance status due to toxicity[33,39,40]. Furthermore, since failing to complete therapy or undergo surgical resection is associated with a worse prognosis, having a patient-centered approach to understand potential barriers to completion is essential. As we have demonstrated in this study, patients experience both physical and emotional symptoms during treatment and require a team approach with the help of ancillary services to help complete therapy. Involvement of patient navigators, social workers, nutritionists, and physical therapists to address patient concerns and symptoms may aid to improve the high attrition rate in patients receiving NT. Previous research has highlighted patient dissatisfaction with the lack of access to counseling services, support groups, and educational tools[41].

There are several limitations to our study. Although our study reached theme saturation, the relatively small sample size and single institution design means that the findings may not be generalizable to all patients with PDAC who are receiving NT. Additionally, our study includes patients with PR, BR and LA disease where larger sample sizes are required to investigate if the patient experience differs according to anatomic stage (e.g., patients with LA disease may have lower expectations of undergoing resection and/or greater burden of cancer-related symptoms than patients with PR disease.) Finally, it is unclear if the patient experience is temporal-dependent and since interviews were performed at a single time during NT, future research may focus on longitudinal evaluations of the patient experience.

In conclusion, this is the first qualitative study to characterize the experience of patient’s receiving NT for localized PDAC. Our findings clarify the lack of familiarity with the concept of NT prior to initiating treatment, the unique care needs of patients receiving NT, and recommendations to improve the delivery of cancer care in the neoadjuvant setting. These data provide a framework to allow for a better understanding of the patient experience during NT and highlight opportunities for patient-centered interventions aimed at improving quality and quantity of life outcomes of those with PDAC.

The authors extend their sincere appreciation to all participants of this study who shared their experience with us. We thank Angela Sarna for her assistance with participant recruitment and administrative support. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.