Secondary Malignancies: Who Is at Risk and Why?

Marijke Vroomen Durning, RN | April 19, 2017
Lucie M. Turcotte, MD, MPH

Lucie M. Turcotte, MD, MPH

The words "You have cancer" have a devastating effect on patients and their families. The diagnosis throws them into a previously unknown world of tests, treatments, and more tests. Once patients have gone into remission and are hopefully cured, they try to go back to their lives and put their cancer experience behind them. Given all they have been through, however, imagine how difficult it must be to hear those words again when a secondary malignancy is diagnosed.

As the population of cancer survivors has grown, so has the risk that patients will develop— and succumb to—a second cancer. An estimated 19% of cancers diagnosed in 2005 to 2009 were found among patients with a prior history of cancer, compared with 9% of diagnoses from 1975 to 1979.1 Among those are secondary malignancies, defined as cancers that are not recurrences of the first malignancy or related to it. The role that the therapy used to treat the first cancer might play in the development of a secondary cancer continues to be a source of clinical investigation.

Anyone who has been treated for cancer is at risk of developing a secondary cancer, but as with most conditions, the possibility is higher in certain groups. The largest at-risk group comprises childhood cancer survivors, who may go on to develop another cancer in adolescence or adulthood. For adults, there is a complex interplay of factors including the type of first and second cancer, patient age, and risk factors including primary cancer treatment, environmental and lifestyle hazards, and genetic susceptibility.1

At-Risk Groups

Many secondary cancers among childhood cancer survivors are known to be related to treatment. However, some also occur because the children may have an underlying genetic predisposition that puts them at higher risk for developing cancer in the first place, Lucie M. Turcotte, MD, MPH, a pediatric hematologist/oncologist and assistant professor in the Division of Pediatric Hematology and Oncology at the University of Minnesota in Minneapolis, said in an interview with OncologyLive®.“We know there are specific genetic syndromes in which children are at higher risk for multiple types of cancers.”

In addition, the cells of growing children tend to be especially susceptible to the effects of radiation, in particular and, to a lesser extent, to the chemotherapy used to treat cancer, Ari VanderWalde, MD, MPH, director of clinical research, West Cancer Center, and associate vice chancellor of research at the University of Tennessee Health Science Center in Memphis, explained in an interview. “It’s one of the reasons that cancer can be cured more often in younger patients, but at the same time because their cells are so susceptible to the effects of these cancer treatments, these cells can mutate more and ultimately develop more cancer.”

There is also the obvious reason why child- hood survivors have a higher incidence of second cancers: their age. “Generally, survivors of childhood malignancy have a lot more years of life left, during which they can develop cancer,” VanderWalde said.

Children are not the only patients at risk, however. Adults who have specific types of primary cancer may also go on to develop secondary malignancies, regardless of their age. A systematic review and meta-analysis of 21 studies published in the BMJ in 2016 found that although the absolute rates of developing another cancer were low, patients with prostate cancer who were treated with radiotherapy had a higher risk of developing second malignancies of the bladder, colon, and rectum compared with patients who did not undergo radiation therapy.2 “The odds of a second cancer varied depending on type of radiotherapy: treatment with external beam radiotherapy was consistently associated with increased odds while brachytherapy was not,” Wallis et al wrote.

The location of the original cancer also is important. With prostate cancer, the most common areas for second cancers are in the lower body, but a study of 1257 patients who had squamous cell carcinoma of the head and neck that found the most common secondary malignancy among this group to be cancer of the larynx.3 Patients who had oral cancer also were more likely to develop a secondary cancer in the head and neck or esophagus.3

More specifically, survivors of head and neck cancer had up to a 27% higher risk of having a secondary cancer compared with the general population.4 The most common secondary cancers for this group were lung cancer and esophageal cancer. The most common cancers are of the upper respiratory tract or digestive tract (40% to 59%), lung (31% to 37.5%), and esophagus (9% to 44%).


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