Surviving Cancer Ups Risk of Dying from a Subsequent Primary Cancer

The risk of developing and dying from a subsequent primary cancer (SPC) was significantly higher among adult survivors of a first primary cancer (FPC) compared with the general U.S. population, a comprehensive, retrospective analysis has shown.

Among men who survived their FPC, excluding those with prostate cancer for at least 5 years, there was an 11% higher risk of developing an SPC (standardized incidence ratio [SIR] 1.11 [95% CI, 1.10-1.12]) and a 45% higher risk of dying from it (standardized mortality ratio [SMR] 1.45 [95% CI, 1.43-1.46]) compared with the general population, Hyuna Sung, PhD, American Cancer Society, Atlanta, Georgia, and colleagues reported in JAMA.

And the risk of developing any SPC was significantly higher for 18 of some 30 FPC types among men, while the risk of men dying from any SPC was significantly higher for 27 of 30 FPC types.

Among women who survived their FPC for at least 5 years, there was a 10% higher risk of developing an SPC (SIR 1.10 [95% CI, 1.09-1.11]) and a 33% higher risk of dying from it (SMR: 1.33 [95% CI, 1.32-1.34]). Their risk of developing any SPC was significantly higher for 21 of some 31 FPCs, while the risk of women dying from any SPC was significantly higher for 28 out of the same 31 FPC types.

“[N]ew malignancies among cancer survivors (i.e., subsequent primary cancers [SPCs]) between 2009 and 2013 comprised a substantial proportion of the total incidence of cancers, ranging from 11% in younger adults (aged 2—64) to 25% in adults aged 65 years and older,” Sung and colleagues observed. “[These] findings emphasize the importance of ongoing surveillance and efforts to prevent new cancers among survivors.”

1.54 Million Survivors

The cohort included 1.54 million survivors diagnosed with a FPC between 1992 and 2011 who had survived at least 5 years following their original diagnosis. The mean age of survivors was 60.4 years, although 41% were 65 years or older at the time of their first cancer diagnosis. The mean follow-up following the first 5 years after the original diagnosis was 7.3 years.

Among the many FPC types, the greatest SIR in men was seen after an original diagnosis of laryngeal cancer (SIR 1.75; 95% CI, 1.68-1.83), followed by survivors of Hodgkin lymphoma (SIR 1.59; 95% CI, 1.47-1.72).

The highest SIR following the original diagnosis in women was again seen after the diagnosis of laryngeal cancer (2.48; 95% CI, 2.27-2.72), followed by a FPC diagnosis of esophageal cancer (1.89; 95% CI, 1.58-2.25), the researchers reported, and noted that the greatest SMR among men was seen after a FPC of gallbladder cancer (3.82; 95% CI, 3.31-4.39) while among women, the highest SMR was seen after an FPC diagnosis of laryngeal cancer (4.56; 95% CI, 4.11-5.06).

Interestingly, the overall SIRs in men were significantly lower for prostate cancer (SIR 0.91; 95% CI, 0.91-0.93), were not significantly different for colorectal cancer, and were slightly higher for bladder cancer (SIR 1.08; 95% CI, 1.06-1.11).

Similarly, the SMR was significantly lower for prostate cancer (SMR 0.90; 95% CI, 0.89-0.91), but this time, the SMR rate was significantly higher for colorectal cancer (SMR 1.11; 95% CI, 1.09-1.15) and for bladder cancer (SMR 1.31; 95% CI, 1.28-1.35), Sung and colleagues observed.

Both SIRs and SMRs were significantly higher for breast cancer in women (SIR 1.06; 95% CI, 1.05-1.08; SMR 1.13; 95% CI, 1.11-1.15). Similarly, the SIR and SMR were significantly higher for colorectal cancer (SIR 1.04; 95% CI, 1.02-1.07; SMR 1.15; 95% CI, 1.12-1.20). The same was true for uterine cancer (SIR 1.03; 95% CI, 1.01-1.06; SMR 1.09; 95% CI, 1.05-1.13).

The risk of developing and dying from an SPC was also significantly lower in male survivors of melanoma of the skin.

“Among all survivors, the 4 SPCs that contributed most to the total incidence of SPCs were lung (19.1%), prostate (13.7%), urinary bladder (11.1%), and colorectal cancers (10.1%),” investigators noted.

The 4 SPCs that contributed most to total SPC mortality in turn were lung cancer at approximately one-third in both men and women, colorectal cancer at almost 9% in men, pancreatic cancer at 8.5% in men and 9.4% in women, and non-Hodgkin lymphoma in men at 6% and breast cancer at approximately 6% in women.

Cancers related to both smoking and obesity made up a substantial proportion of the overall incidence of SPC and mortality among all adult survivors.

For example, 12 smoking-related cancers were included in the analysis. Among survivors of any one of these FPCs, “the risks of developing any subsequent smoking-related cancers were statistically significantly higher for all cancers except liver cancer in men and stomach cancer and acute non-lymphocytic leukemia in women,” the authors pointed out.

Twelve obesity-related cancers were also included in the analysis. Among survivors of any one of these 12 FPCs, “the risk of developing any subsequent obesity-related cancers were statistically significantly higher among male survivors of pancreatic, gallbladder, thyroid, and colorectal cancers and among female survivors of thyroid, kidney, uterine corpus, and breast cancer,” the investigators wrote, adding that most of the excess risk of developing a SPC among FPC survivors was due to either host factors, such as age, or to lifestyle factors, such as smoking, obesity, and infection, notably with the human papilloma virus (HPV).

Since other studies of breast and colorectal cancer survivors have shown that the risk of developing an obesity related SPC occurred among those with excess body weight, “maintenance of healthy body weight may reduce the risk of SPCs,” they said.

“Survivorship care may [thus] require greater focus on lifestyle factors, including weight management, physical activity and healthy eating,” they added. Similarly, primary prevention for cancers of the oral cavity and pharynx, the anus, and the cervix is possible through the use of HPV vaccination.

Limitations of the study include the fact that the authors did not examine risk associated with radiation or chemotherapy treatment, as that information is not available through registry data as was used in the current analysis.

All Cancer Survivors

Commenting on the findings, lead editorialist Patricia Ganz, MD, UCLA Fielding School of Public Health in Los Angeles, and colleagues pointed out that the frequency with which SPCs occur after a wide variety of cancer diagnoses suggests that primary care physicians should routinely consider the risk of SPCs in all cancer survivors.

“The 5-year survival time point often marks a clinical transition when many patients are no longer followed-up in oncology specialty practices and must rely on their primary care clinicians as their main source of medical care,” Ganz and colleagues wrote. “[Thus], clinicians have an important role in counseling regarding behavioral and lifestyle risk factors that may attenuate the risk for SPCs, and this should be a priority.”

The editorialists also pointed out that “special considerations” need to be given to young adult cancer survivors when it comes to subsequent cancer screening for early detection of SPCs.

In addition, targeted cancer screening for SPCs is vital for early detection of SPC in the same patient population, as young cancer survivors in fact have lower survival odds compared with older patients diagnosed with the same SPC, Ganz and colleagues noted.

There also must be “no missed opportunities” during survivorship care for breast, colorectal, and cervical cancer screening, as recommended by the U.S. Preventive Services Task Force. This should include lung cancer screening for patients with a history of smoking and a prior tobacco-related cancer.

Although Ganz and colleagues acknowledged that changes in at-risk tissues are unlikely to be reversed in smoking and infection-related SPCs, “there are still opportunities for interventions aimed at decreasing smoking to reduce the length of tobacco exposure, especially in younger cancer survivors, potentially mitigating risk,” they wrote. “Similarly, counseling to prevent obesity and to promote weight loss in survivors is a critical component of high-quality primary care for cancer survivors.”

1. The risk of developing and dying from a subsequent primary cancer (SPC) among adults who have survived a first primary cancer was greater than the risk seen in the general U.S. population.

2. Since a dozen cancers related to both smoking and obesity each made up a sizeable proportion of SPC incidence and mortality, a greater focus on lifestyle management is required to reduce the risk of SPCs.

Pam Harrison, Contributing Writer, BreakingMED™

Cat ID: 120

Topic ID: 78,120,730,120,935,192,925