In 1996, the National Comprehensive Cancer Network® (NCCN®) published its first set of Clinical Practice Guidelines in Oncology® covering eight tumor types. Guidelines are now published for more than 60 tumor types, subtypes, and topics. During the NCCN’s 27th Annual Conference, which was again held virtually, updates to the NCCN Guidelines were presented for several tumor types. We briefly described here the latest key recommendations.
Inaugural Guidelines for Ampullary Adenocarcinoma
“Ampullary adenocarcinoma may have a slightly better prognosis than pancreas cancer, but it remains a highly lethal disease.”
—Stephen W. Behrman, MD
Stephen W. Behrman, MD
Ampullary adenocarcinoma is a rare cancer that accounts for 0.2% of all gastrointestinal malignancies. There are two main histologic subtypes: intestinal, which resembles adenocarcinoma of the colon, and pancreaticobiliary, which resembles pancreatic cancer. Treatment of this cancer is based on the subtype.
The first version of the NCCN Guidelines for Ampullary Adenocarcinoma was released on March 9, 2022. Stephen W. Behrman, MD, Professor of Surgery at the University of Tennessee Health Science Center, Memphis, described ampullary adenocarcinoma at the conference and gave attendees an overview of these new recommendations. Here are some highlights from the first version of these guidelines:
Colorectal Cancer Screening
“The first and most significant change in our guidelines was a lowering of the initial screening age for average-risk individuals from 50 to 45. The second biggest change is to extend the surveillance period from what was 5 to 7 years to 10 years now for patients with only one to two small tubular adenomas.”
—Reid M. Ness, MD, MPH
Reid M. Ness, MD, MPH
The NCCN Guidelines on Colorectal Cancer Screening reflect significant changes that will spare some patients unnecessary interventions and, in other cases, facilitate earlier detection of colorectal cancer. The updated recommendations were presented at the NCCN 2022 Annual Conference by Reid M. Ness, MD, MPH, Assistant Professor of Medicine at Vanderbilt-Ingram Cancer Center, Nashville.
The changes to the guidelines pertain primarily to the age at which screening is initiated and to surveillance intervals that are dependent on findings on the index colonoscopy. They include:
Dr. Ness explained that the impetus for lowering the initial screening age is based on well publicized trends in colorectal cancer incidence since the implementation of colorectal cancer screening in 1980. Over time, there has been a 40% reduction in colorectal cancer incidence but a rising incidence of the cancer in adults under age 50. Some screening experts argued that the cost of earlier screening would result in “unacceptably high” absolute costs, he said. “Despite these concerns, our committee felt that the cost-to-benefit trade-off was acceptable,” he said, further noting that all national colorectal cancer screening guidelines have now been “brought into accord.”
Locoregional Management of Early-Stage Breast Cancer
“For clinically N0 patients with one to two positive sentinel nodes after upfront surgery, we should be moving away from using nomogram estimations of additional nodal risk to support performing axillary dissection, since axillary radiation provides similar therapeutic outcomes with significantly less lymphedema. Instead, we should be shifting our thought process toward considering axillary radiation for all eligible patients in whom dissection is not needed for additional treatment considerations.”
—Meena S. Moran, MD
Meena S. Moran, MD
A. Marilyn Leitch, MD
The updated NCCN Guidelines for the locoregional management of early-stage breast cancer contain numerous new recommendations, especially for radiotherapy. These were presented by Meena S. Moran, MD, Professor of Therapeutic Radiology at Yale School of Medicine and Chief of the Yale Breast Radiotherapy Program for the Yale New Haven Hospital Health Care System, and A. Marilyn Leitch, MD, Professor of Surgical Oncology and the S.T. Harris Family Distinguished Chair in Breast Surgery at the University of Texas Southwestern Simmons Comprehensive Cancer Center, Dallas.
The following are the key changes for early-stage breast cancer:
HER2-Negative Breast Cancer
“These BRCA1/2 mutations are not frequent, but if you find these patients, a PARP [poly (ADP-ribose) polymerase] inhibitor may be something to consider. We can now make the case that more patients should be getting genetic testing.”
—William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
The systemic treatment of HER2-negative breast cancer is largely governed by whether the patient is hormone receptor–positive or –negative. In the past several years, the treatment landscape was essentially revolutionized by the emergence of the cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in the hormone receptor–positive subset and by immunotherapy for patients with hormone receptor–negative, HER2-negative tumors. In contrast, the more recent advances have been tweaks that help escalate treatment where necessary and de-escalate it whenever possible.
Some of these small but important changes to the guidelines were reviewed at the conference by William J. Gradishar, MD, FACP, FASCO, Chief of the Division of Hematology and Oncology and the Betsy Bramsen Professor of Breast Oncology at Northwestern University Feinberg School of Medicine and Director of Robert H. Lurie Comprehensive Cancer Center’s Maggie Daley Center for Women’s Cancer Care, Chicago.
The NCCN Guidelines for HER2-Negative Breast Cancer, focusing on systemic therapy, include the following updates:
Vaccination for Patients With Cancer and Cancer Survivors
“Patients with cancer are vulnerable to infection while under active treatment, as chemotherapy, radiation therapy, and immune-altering therapies can lead to neutropenia, lymphopenia, and altered immune competence. Immune deficits can persist for months or even years after treatment.”
—Maria Alma Rodriguez, MD
Maria Alma Rodriguez, MD
Maria Alma Rodriguez, MD, Professor of Medicine, The University of Texas MD Anderson Cancer Center, Houston, detailed the appropriate immunization practices in these highly susceptible populations. Here are the key additions and updates to the NCCN Guidelines for Survivorship regarding immunizations and infections:
For all cancer survivors:
If some special circumstance or risk factor is present:
For survivors who underwent cellular therapy:
For all other survivors:
The commonly used live attenuated varicella vaccine (single or combined with the measles, mumps, and rubella [MMR] vaccine) is now contraindicated or to be used with caution in actively immunocompromised survivors themselves and their close contacts. Moreover, the guideline states that all live virus vaccines are contraindicated in patients with cancer and immunocompromised survivors and should be avoided as possible.
“A key factor in selecting therapy for multiple myeloma is whether the patient is refractory to lenalidomide.”
—Shaji K. Kumar, MD
Shaji K. Kumar, MD
Multiple new treatments have been approved for multiple myeloma in the past few years, but their optimal use is still being explored. As patients become refractory to one, then another, what is the proper sequencing? These and other questions were addressed by Shaji K. Kumar, MD, the Mark and Judy Mullins Professor of Hematologic Malignancies at the Mayo Clinic Cancer Center, Rochester, Minnesota.
Dr. Kumar indicated the following are the latest additions to the NCCN Guidelines for Multiple Myeloma:
For early relapse, there are new preferred options:
For previously treated patients:
For primary treatment in transplant candidates:
For primary treatment in nontransplant patients:
Relapsed/Refractory Indolent B-Cell Lymphomas
“Tazemetostat is a good option in patients who are elderly or those who do not have bulky or rapidly progressive disease, particularly those with wild-type EZH2 who may do well with responding or stable disease for a period of time.”
—Ann S. LaCasce, MD, MMSc
Ann S. LaCasce, MD, MMSc
Ariela Noy, MD
The NCCN Guidelines for B-Cell Lymphomas—in particular the indolent subtypes follicular and marginal zone lymphomas—underwent no major revisions in the past year. However, the panel made a few changes in systemic therapy for relapsed or refractory disease. These revisions were discussed at the conference by Ann S. LaCasce, MD, MMSc, and Ariela Noy, MD. Dr. LaCasce is Director of the Dana-Farber/Mass General Brigham Fellowship in Hematology/Oncology at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School, Boston. Dr. Noy is an Attending and Professor of Medicine at Memorial Sloan Kettering Cancer Center and Weill Medical College, New York.
The NCCN Guidelines now state:
Cancer Screening and Surveillance Testing for Older Adult Cancer Survivors
“For cancer screening, the benefits are pretty clear. We’re looking for a lower risk of death from cancer, as well as diagnosis of cancer at an earlier stage, leading to less intensive treatments. But what are the harms? They include false-positive tests, unnecessary biopsies, incidental findings—which are more common with imaging modalities for screening—and overdiagnosis.”
—Nancy L. Keating, MD, MPH
Nancy L. Keating, MD, MPH
With regard to both cancer screening and surveillance testing in older adult cancer survivors, the recently updated NCCN Guidelines for Older Adult Oncology aim to avoid excessive screening and overdiagnosis. The recommendations take into account factors such as life expectancy, health status, and patients’ goals and values as well as individual benefit vs harm. These changes were presented by Nancy L. Keating, MD, MPH, Professor of Health Care Policy and Medicine at Harvard Medical School and a physician at Dana-Farber/Brigham and Women’s Cancer Center, Boston.
In terms of cancer screening for adult cancer survivors, the NCCN Guidelines for Older Adult Oncology incorporate life expectancy and the patient’s fitness and desire for further anticancer treatment in its recommendations:
The NCCN Guidelines approach routine surveillance testing for older adult cancer survivors with no evidence of disease in a similar fashion:
“Here, the life expectancy cutoff is 5 years, because of the concern that patients who’ve had a history of cancer might actually be at higher risk of a cancer recurrence, so surveillance testing might be beneficial,” Dr. Keating noted. “If life expectancy is less than 5 years, patients are unlikely to benefit from surveillance testing for finding a recurrence or a new cancer, but if life expectancy is more than 5 years, then a discussion with the patient about goals and values is important.”
DISCLOSURE: Dr. Behrman, Dr. Ness, Dr. Moran, Dr. Keating, Dr. LaCasce, Dr. Noy, and Dr. Rodriguez reported no conflicts of interest. Dr. Leitch has consulted for AstraZeneca and Puma Biotechnology. Dr. Gradishar has served as a consultant or advisor to Genentech/Roche, AstraZeneca, MacroGenics, Seattle Genetics, and Merck. Dr. Kumar disclosed financial relationships with AbbVie, Amgen, BeiGene, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Karyopharm, Regeneron, Roche, Sanofi-Aventis, and Takeda Pharmaceuticals North America.