Author: Kristin Jenkins
In the United States, men and women who survive adult-onset cancers for at least 5 years are at significantly increased risk of developing and dying from new primary cancers, particularly those driven by smoking and obesity, a new study shows.
“This was disturbing but at the same time provides tremendous opportunities for cancer prevention and control, not only to mitigate the subsequent cancer risk but also to minimize comorbidities,” lead author Hyuna Sung, PhD, of the American Cancer Society in Atlanta, Georgia, told Medscape Medical News.
“The importance of smoking cessation, weight control, physical activity, and other factors consonant with adoption of a healthy lifestyle should be consistently emphasized to cancer survivors,” Sung said.
Results from a retrospective analysis of the most recent Surveillance, Epidemiology, and End Results (SEER) data from a cohort of 1.5 million survivors of first primary cancers (FPCs) show that male survivors — excluding those with prostate cancer — had a 45% higher risk of dying from any subsequent primary cancer (SPC) compared with men in the general population without a history of cancer.
Female survivors had a 33% higher risk of any SPC-related mortality, the study authors report in the Journal of the American Medical Association.
A significant proportion of the total incidence and mortality from SPCs was made up of smoking- or obesity-associated SPCs, the analysis shows.
“The risks of smoking-related SPCs were commonly elevated following many types of smoking-related FPCs, suggesting the role of smoking as a shared risk factor,” the researchers say.
Overall, four common smoking-related SPCs — lung, urinary bladder, oral cavity/pharynx, and esophagus — accounted for 26% to 45% of the total SPC incidence and mortality. Lung cancer alone accounted for 33% of the SPC-associated mortality in men and 31% of the mortality in women.
As previously reported by Medscape Medical News, second lung cancers occurring up to a decade after the first are on the rise, supporting long-term surveillance in survivors.
The current study also shows that in both men and women, four common obesity-related cancers — colorectal, pancreatic, uterine and liver — comprised 22% to 26% of the total SPC mortality.
“Survivorship care guidelines recommending health promotion need wider dissemination and implementation in oncology and primary care,” the study authors write about recommendations from the cancer society.
The investigators point out that in spite of evidence that a body mass index beyond the range of normal in survivors of breast and colorectal cancer increased risk of second obesity-associated cancers, many patients say they have never discussed with a doctor how to modify their lifestyle for a healthy body weight.
In 2018, the National Cancer Institute (NCI) reported that 67% of US cancer survivors were overweight or obese, Sung and colleagues note.
In an accompanying editorial, Patricia Ganz, MD, and Jacqueline Casillas, MD, of the David Geffen School of Medicine at UCLA, Los Angeles, California, agreed that the current study findings indicate “research and implementation of evidence-based interventions to promote smoking cessation and energy balance are a priority.”
The editorialists also point to issues of poor communication in clinical practice. “Among patients who survive a primary cancer, concern about recurrence, especially metastatic disease, is extremely common; however, information about future risk for subsequent primary cancers is seldom communicated to these patients, leading to missed opportunities to prevent or detect SPCs at an early stage.”
Close collaboration with primary care physicians during the early follow-up period is “a must,” Ganz told Medscape Medical News.
Oncologists should start the discussion right after initial treatment, when survivors are looking for ways they can prevent cancer recurrence or the development of new cancer, Ganz suggests.
“The ones I worry about the most are the young adults who could really benefit from the prevention outlook that primary care clinicians espouse,” she says, citing a 2016 study.
“If they continue to smoke or gain weight, that increases their risk of SPCs but also of comorbid chronic conditions…so it’s very important for them to get into the hands of a primary care physician. This issue is in the primary care provider court.”
Reorganization of Care and Payment Needed
For the study, Sung and colleagues analyzed data from 12 SEERS registries of FPC survivors diagnosed between 1992 and 2011. All patients had survived 5 years or more after initial diagnosis and had been followed to the end of 2017. Mean follow-up was 7.3 years.
The incidence and mortality of SPCs per 10,000 person-years were expressed as a standardized incidence ratio (SIR) and standardized mortality ratio (SMR) compared with expected risk in the general population.
A total of 30 FPC types were identified, including 12 smoking-related cancers and 12 obesity-related cancers.
In men, the highest risk of developing and dying from any SPC was estimated among survivors of laryngeal cancer (SIR 1.75) and gallbladder cancer (SMR 3.82), and among female survivors of laryngeal cancer (SIR 2.48; SMR 4.56).
Compared with men in the general population without a history of cancer, male survivors had an overall risk of developing any SPC that was significantly higher for 18 of the 30 FPC types. Male survivors also had an overall mortality risk for any SPC that was significantly higher for 27 of 30 FPC types.
This increased risk pattern looked much the same in female survivors when compared with women in the general population without cancer. The overall risk of developing and dying from any SPCs was significantly higher in female survivors for 21 and 28 of 31 FPC types, respectively.
The most common SPCs — after lung cancer — included colorectal cancer (8.8% of male survivors); pancreatic cancer (8.5% of male and 9.4% of female survivors); non-Hodgkin lymphoma (6% of male survivors); and breast cancer (5.8% of female survivors).
The study also shows that the risk for alcohol- and infection-related cancers was significantly higher following a diagnosis of most alcohol- and infection-related cancers.
These findings also have implications for reducing the economic burden of care, Sung and colleagues say.
“With the growing number of long-term survivors, the costs of treating patients with multiple primary cancers will increase, amplifying financial burden for cancer survivors and their families, particularly among elderly persons who may be living on fixed incomes. This consideration also has implications for the Medicare program, the primary payer for the population aged 65 years and older, as well as other health care payers,” the authors write, citing related financial research.
When it comes to improving outcomes for cancer survivors, “SPCs are just the tip of the iceberg,” Ganz warns. We will need some reorganization of healthcare delivery and payment schemes to make it happen, I think.”
She notes that recommendations for long-term survivorship care after cancer treatment were summarized following the 2017 National Cancer Policy Forum Workshop. Since then, “there has not been much movement,” Ganz says.
Current NCI-funded studies of innovative survivorship care planning and implementation are important, but results will not be forthcoming for at least 5 more years, she points out. “We really need more immediate efforts to transform care delivery.”
This study was funded by the American Cancer Society. Sung, study coauthors, and editorialists Ganz and Casillas have disclosed no relevant financial relationships.
JAMA. Published online December 22, 2020. Full text