1 in 12 Chance of Second Cancer in Many Survivors

Nick Mulcahy

July 21, 2016

In the United States, more than 8% of adults diagnosed with the most common cancers develop a second malignancy (of any type, including rare cancers), according to an analysis of US data from the last two decades.

The top-diagnosed second malignancy was lung cancer (18% of all second primaries), followed by colorectal cancer (12%), prostate cancer (9%), and bladder cancer (8%).

Second cancers were often lethal: More than half of patients (55%) died of their second cancer, while 13% died of their first cancer.

Oncologists, other specialists and primary care providers should be on the lookout not just for recurrence of an initial cancer but for second cancers, lead author Nicholas Donin, MD, a urologist at the David Geffen School of Medicine, University of California, Los Angeles, told Medscape Medical News.

The study was published online July 5 in Cancer.

Dr Donin and colleagues identified more than 2.1 million adults diagnosed with a primary malignancy from the 10 most common cancer sites (prostate, breast, lung, colon, rectum, bladder, uterus, and kidney, along with sites affected by melanoma and non-Hodgkin lymphoma) in 1992–2008 from Surveillance, Epidemiology, and End Results data.

From that group, 170,865 (8.1%) developed a second primary malignancy; mean follow-up was greater than 6 years in all primary cancer types (except for primary lung cancer, which was 4.18 years).

Patients with bladder cancer had the highest cumulative incidence, with 19% having a second cancer at 10 years and 34% at 20 years. Most commonly, that second malignancy was lung cancer (25% of the time).

"Bladder cancers are often associated with a significant smoking history. Urologists should think about referring these patients for lung cancer screening," Dr Donin explained.

It is understandable that patients with bladder cancer had the highest rate of a second primary cancer, he also observed.

Most bladder cancers are of low grade and stage and not lethal. The 5-year relative survival from bladder cancer is 80%, and the disease is highly prevalent (in 2012, there were 577,403 bladder cancer survivors in the United States).

Lethal Second Cancers

"I am not surprised by the percentage of second cancers among survivors for a number of reasons," said Eric Horowitz, MD, a radiation oncologist at Fox Chase Cancer Center in Philadelphia, Pennsylvania, who was not involved in the study.

"Our primary treatments have gotten so much better, and we have more survivors living for longer periods of time," he told Medscape Medical News.

Dr Horwitz reminded clinicians to "still do other cancer screenings" in cancer survivors. "Lung cancer patients still need a colorectal cancer screening," he said.

Lung cancer patients still need a colorectal cancer screening. Dr Eric Horowitz

The researchers also found that second cancers are often lethal.

In the group of patients with 2 primary cancers, a lung cancer diagnosis was most deadly, accounting for 12% of all deaths in this group, which amounted to more overall deaths than the combined total from melanoma, bladder cancer, thyroid cancer, kidney cancer, or endometrial cancer that were second primaries.

The prominence of lung cancer both as a second cancer and as a cause of death was arresting, said Dr Dobin.

"This didn't start out as a lung cancer paper but it was an eye-opener," he said, adding that smoking cessation becomes especially important in cancer survivors.

Dr Dobin also hypothesizes that bladder cancer might be a marker for high-risk lung cancer. "It's a question worth asking," he said, citing a potential research project.

It's a question worth asking. Dr Nicholas Donin

The study authors say that cancer survivors may be "especially susceptible" to developing second primary malignancies because of a variety of unique factors, including genetic syndromes, common etiologic exposures (especially smoking), and the late effects of chemotherapy and radiotherapy, say the authors.

But in commenting on the study, Dr Horwitz argued that second malignancies from cancer treatment are "more an issue with survivors of childhood cancers." This study did not include patients with cancer under age 18 years. He argued that "there is a tiny risk of second cancer from radiation treatment."

The study authors acknowledged that there was a chance that some second cancers were actually metastases of initial cancers.

However, this was unlikely, said the authors, because they excluded cases in which the second primary malignancy was diagnosed within 1 year of the first malignancy (n = 557,346). Also, many common secondary malignancies (eg, prostate, breast, colorectal, and bladder cancer and non-Hodgkin's lymphoma) are in unlikely sites for metastases.

This study was supported, in part, by the Urology Care Foundation Research Scholars Program, American Cancer Society Postdoctoral Fellowship, National Institutes of Health Loan Repayment Program, and STOP Cancer Foundation. The study authors have disclosed no relevant financial relationships.

Cancer. Published online July 5, 2016. Abstract

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick.

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