ASCO and its members have heightened efforts in the last year to develop practice guidelines for gastrointestinal cancers.
These efforts were driven in part by advancements in treatments, including the increasing ability to guide care through the use of biomarkers and genetic testing. Guidelines cover the spectrum from common cancers, such as colorectal cancer (CRC), to cancers with relatively low incidence rates, such as pancreatic cancer.
Between 5%-6% of patients with CRC have an underlying hereditary CRC syndrome. A recent ASCO endorsement focused on recommendations for diagnosis and treatment of these individuals. ASCO is creating broader guidelines regarding the use of a panel of biomarkers to guide treatment of CRC.
Incidence of pancreatic cancer, a less common type of cancer than CRC, is rising. By 2030, pancreatic cancer is projected to become the second leading cause of cancer-related death, largely because screening and treatment lag behind more common malignancies, such as breast and prostate cancers. The ASCO Pancreatic Cancer Working Group aims to alter that dire predication by creating the first pancreatic cancer guidelines.
Guideline on Hereditary CRC Syndromes
In December 2014, ASCO endorsed the European Society for Medical Oncology (ESMO) guideline on screening for hereditary CRC syndromes, as well as on the management and prevention of CRC in individuals with these syndromes.2 The guideline focuses on Lynch syndrome and APC-associated familial adenomatous polyposis (FAP or classic FAP), the most common hereditary CRC syndromes, implicated in 2%-3% and less than 1% of all CRCs, respectively.
ASCO’s endorsement “raises awareness that for every patient diagnosed with CRC, an assessment needs to be made about how likely it is that this patient’s cancer is due to an inherited predisposition,” said Elena M. Stoffel, MD, of the University of Michigan Health System, co-chair of the endorsement panel.
The guideline recommends screening tumors for DNA mismatch repair (MMR) deficiency using either immunohistochemistry for MMR proteins or microsatellite instability to assess if patients with CRC have Lynch syndrome. Testing should be considered for patients with CRC of all ages, although the ESMO guideline suggests performing tumor screening in all patients diagnosed with CRC before age 70 and selectively in patients over 70, limiting to those who meet one of the Bethesda guidelines criteria.
Lynch syndrome can be confirmed by sequencing of germline DNA for mutations in the MMR gene in individuals screened positive for tumors with DNA MMR deficiency. Tumor immunohistochemistry can help inform which gene is most likely to be mutated, corresponding to proteins with absent expression.
Among individuals with more than 10 colorectal adenomas, the guideline recommends considering genetic testing for germline mutations in APC, found in FAP and AFAP syndromes, and MUTYH, found in AFAP and MYH-associated polyposis syndromes.
The guideline includes a number of recommendations pertaining to surveillance of individuals with hereditary CRC syndromes. Patients with Lynch syndrome should undergo a colonoscopy every 1-2 years, beginning at age 20-25 or 5 years before the youngest case in the family, whichever is earlier. Increased surveillance for endometrial, ovarian, and gastric cancers is also recommended.
One of the few differences between ESMO’s guideline and ASCO’s endorsement pertains to the treatment of individuals with FAP. Whereas the ESMO guideline recommends screening FAP mutation carriers by sigmoidoscopy every 2 years starting at age 12-14, ASCO recommends performing a colonoscopy as frequently as every year starting at age 10-11. A colonoscopy facilitates visualization and removal of proximal polyps. Individuals with AFAP who carry APC mutations should undergo colonoscopy every 2 years or more frequently depending on polyp burden, starting at age 18-20.
ASCO’s endorsement “demonstrates that there is consensus among experts who treat these patients both in the United States and internationally,” Dr. Stoffel said. “This is important in influencing health policy and helping to get this type of care covered by insurance.”
Medicare currently only covers genetic testing for patients with more than 20 polyps. It covers genetic testing for individuals with Lynch syndrome who are diagnosed with a cancer, but it does not cover predictive genetic testing for individuals who are cancer-unaffected even when at-risk for inheriting the family mutation.
Development of Guidelines for GI Cancer Biomarkers
ASCO is updating its provisional clinical opinion on testing patients with metastatic CRC for mutations in the KRAS gene to guide the use of anti-EGFR monoclonal antibody therapy.
The previous provisional clinical opinion, published in 2009, recommends that patients who have mutations in KRAS codons 12 or 13 not receive anti-EGFR therapy, cetuximab or panitumumab.3 The update will include additional KRAS mutations that could help guide anti-EGFR therapy. Numerous studies, including a systematic review by the College of American Pathologists (CAP), are under consideration for the update, which is expected to come out later this year.
ASCO has partnered with CAP, the American Society for Clinical Pathology (ASCP), and the Association for Molecular Pathology (AMP) to create a guideline on the clinical utility of CRC biomarkers for identifying patients for targeted and conventional therapies. It will consider extended RAS, BRAF, and several other biomarkers.
The guideline panel will provide recommendations on the processing of tumor tissue specimens for biomarker testing and identify and make recommendations on additional biomarkers that should be considered for patients with hereditary CRC syndromes. The guideline panel is finishing draft recommendations in preparation for the upcoming open comment period.
ASCO is creating a new guideline on HER2 testing in gastric cancers which, along with CA19-9, is used in clinical practice as a biomarker in this disease site.4 The joint guideline effort between ASCO, CAP, and ASCP is still in the early stages.
Focus on Pancreatic Cancer Guidelines
ASCO is creating a series of guidelines on pancreatic cancer, from diagnosis and management to screening. The first three guidelines will make recommendations about the treatment of three states of pancreatic cancer: resectable, locally advanced (unresectable), and metastatic. Publication of the guidelines is scheduled for late fall 2015.
“[Whereas] until recently, we didn’t have a lot of choices, we now have multiple systemic therapy options for the first-line and second-line setting for metastatic pancreatic cancer, and then we have many questions around preoperative and postoperative treatment,” said Alok A. Khorana, MD, of Cleveland Clinic, who is overseeing the Pancreatic Cancer Working Group. The group is creating the guideline panels and setting the agenda for additional pancreatic cancer guidelines over the next several years.
Current guidelines will address which pancreatic cancers should be considered resectable, and thus candidates for surgery, as opposed to locally advanced. A clearly outlined definition of resectable cancer could help surgeons in their decision making.
“These guidelines will inform a standard accepted practice for their topic so that we can reduce treatment variation in a space where there are data that show a certain treatment is the best approach,” said Manish Shah, MD, of Weill Cornell Medical College, who is on the panels for metastatic and resectable pancreatic cancer.
A goal of the guidelines is bringing attention to the need for more pancreatic cancer research.
“As we develop more clinical trials over the next few years, we can look to these guidelines as a benchmark for what is the current evidence, and what are the knowledge gaps in terms of screening, public health issues, and treatments,” Dr. Khorana said.
Simultaneous guideline creation by three different expert panels will save time because of overlap between the cancer states and will help ensure the same clinical definitions are used in all three guidelines, Dr. Shah said.
Additional innovations include incorporating the patient perspective into guideline creation. Panels will include not only a patient advocate but also a palliative care specialist.
Panels are discussing how patients, and their treatment responses, could differ from typically younger clinical trial participants with less comorbidity. In addition to an expedited development timeline, guidelines will be updated frequently, ideally every 2 years. The ASCO Guidelines wiki will allow readers to suggest changes and submit new evidence.
Pancreatic cancer guideline topics tentatively scheduled for development after the current three guidelines are completed include screening and hereditary risk and management of symptoms, such as obstructive jaundice.
Learn more on ASCO’s guidelines.