By Alok A. Khorana, MD
- It is estimated that pancreatic cancer will become the second-leading cause of death by 2020 based on increased deaths counterpoised against improving mortality for more common solid tumors.
- ASCO’s Clinical Practice Guidelines Committee initiated a Pancreatic Cancer Working Group in 2015 to help standardize the care of people with pancreatic cancer.
- Three Expert Panels were assembled to develop the guidelines, published May 31, 2016, to address the three most common clinical presentations for pancreatic cancer: potentially curable, locally advanced, and metastatic.
The lack of progress in the diagnosis and treatment of pancreatic cancer extends across all settings and presentations. There are currently no screening programs for early detection of pancreatic cancer. As a result, at diagnosis, an overwhelming majority of patients have either metastatic or unresectable disease. Overall 5-year survival in Surveillance, Epidemiology, and End Results datasets, therefore, is only 7.2%. Even for the approximately one-tenth of patients with localized disease, 5-year survival rates are a dismal 27%. Patients who undergo so-called curative resections have a median survival of 20 months under the best circumstances.3 There has certainly been recent good news—greater insights into the biology of pancreatic cancer leading to novel therapeutics,4 and recent incremental improvements in median survival with combination regimens.5 However, there remain major knowledge gaps around key clinical issues: the definition of resectable cancer, neoadjuvant versus adjuvant approaches, the role of radiation therapy and newer radiation technology such as stereotactic body radiation therapy (SBRT), appropriate treatment of locally advanced disease, and sequencing of treatment in metastatic disease.
ASCO’s Pancreatic Cancer Guidelines
Many clinicians recognize that “real-world” patients with pancreatic cancer differ from the study populations of clinical trials. Often, patients seen in the clinic are not eligible for treatment because of underlying frailty, complications from the cancer itself, or multiple chronic conditions that place them at high risk for treatment-related toxicity. Furthermore, pancreatic cancer is a disease of predominantly older people, and an awareness of the special needs of the geriatric population is required. One innovative approach taken in this guideline process was to “embed” palliative medicine and geriatric oncology experts in each Panel to address the myriad issues related to patient care and clinical decision making that clinicians are often confronted with but that are not generally addressed in randomized clinical trials.
Guideline 1: Potentially Curable Pancreatic Cancer
Approximately one-fifth of diagnoses are considered potentially curable—so-called “resectable” or “borderline resectable” cancers for which surgical resection is an appropriate first consideration. However, even defining “resectable” is difficult, with multiple definitions proposed by multiple groups and no randomized trial evidence to support one definition over another. Rather than come to a general, non–evidence-based consensus, the Panel chose a pragmatic approach, categorizing patients as those for whom primary pancreatectomy is recommended versus those for whom preoperative therapy is recommended prior to intended resection. The major clinical issues addressed by the Panel include the initial assessment and workup after diagnosis, selection of patients for primary resection versus preoperative therapy, the appropriate adjuvant regimen, timing of palliative care services, and surveillance after completion of initial treatment. A key recommendation was that multidisciplinary management should be the standard of care. In addition, the Panel emphasized a careful evaluation of the baseline performance status and comorbidity profile, offering clinical trials where available and having a discussion regarding goals of care and support systems with each patient.
Guideline 2: Locally Advanced Pancreatic Cancer
A large subgroup of patients present with locally advanced, unresectable pancreatic cancer but without evidence of metastatic disease. Knowledge gaps include when to treat patients as one would for metastatic disease and when to emphasize local therapy, such as concurrent chemoradiation or SBRT. This Panel addressed multiple clinical issues in this setting including: initial assessment and workup; the appropriate initial treatment approach, selection, and timing of radiation therapy in this setting, including emerging data related to SBRT; extrapolation of “lines” of therapy from the metastatic setting in the absence of data in the locally advanced setting; addressing pain and other symptom burden; and the timing of palliative care services. One key recommendation regarding the latter was that all patients with locally advanced, unresectable pancreatic cancer should have a full assessment of symptom burden, psychological status, and social supports as early as possible—preferably at the first visit. In most cases, the panel felt that this would indicate a need for formal palliative care services.
Guideline 3: Metastatic Pancreatic Cancer
Combination treatment regimens have finally started to show benefit in this setting after nearly 2 decades of failed randomized trials, although many questions remain regarding patient selection and sequencing of regimens. This Panel addressed the following clinical issues: initial assessment and workup, selection of first-line treatment given that both FOLFIRINOX and gemcitabine plus nab-paclitaxel have randomized clinical trials evidence in this setting but without head-to-head comparison, selection of next-line treatment, introducing palliative care, and management of pain and other symptoms.
The panel recommended FOLFIRINOX for patients who met all of the following criteria: ECOG performance status (PS) 0 to 1, favorable comorbidity profile, preference and support system for aggressive medical therapy, and access to chemotherapy port and infusion pump management services. Gemcitabine with nab-paclitaxel was recommended as an alternative first-line regimen for patients with ECOG PS 0 to 1, relatively favorable comorbidity profile, and a preference and support system for relatively aggressive medical therapy. Gemcitabine alone was recommended for patients who either have an ECOG PS of 2 or have a comorbidity profile precluding more aggressive regimens and who wish to pursue cancer-directed therapy. The Panel suggested that patients with an ECOG PS of 3 or higher or with poorly controlled comorbid conditions despite ongoing active medical care should only be offered cancer-directed therapy on a case-by-case basis, and the oncology team’s emphasis should be on optimizing supportive care.
The Panel recommended against the routine use of PET scans. The Panel noted the lack of data regarding optimal duration of cancer-directed therapy and suggested that an ongoing discussion of goals of care and assessment of treatment response and tolerability should guide decisions to continue or hold/terminate cancer-directed therapy.
Moving Pancreatic Cancer Treatment Forward
This first set of comprehensive guidelines from ASCO focused on pancreatic cancer should serve to highlight its rise as a cause of cancer-related death and the slow progress in treatment, particularly when framed against advances made with other major cancers. We believe that funding agencies must focus greater attention on this highly lethal illness, and clinical trialists and scientists must consider more innovative approaches. We hope that this set of guidelines identifies some of the small but real gains made in the past few years as well as the major knowledge gaps that remain.
The overarching themes emphasized by each of these Expert Panels include access to multidisciplinary care (including palliative services) and on not just treating the cancer, but addressing all of the patient’s needs—pain and symptom control, comorbidities, and support systems.
The Pancreatic Cancer Working Group plans to update and continue to add to the portfolio of recommended care options as new topics, and, hopefully, new treatment options arise regarding various aspects of pancreatic cancer care over the next few years. We hope these guidelines will assist busy clinicians in providing the best-possible care to their patients dealing with this very difficult illness.
Acknowledgements: Dr. Khorana is supported by the Sondra and Stephen Hardis Chair in Oncology Research and the Scott Hamilton CARES Initiative.