Chemo Linked to Increased CVD Risk in Testicular Cancer

Veronica Hackethal, MD

August 10, 2015

A small number of men who receive chemotherapy for testicular cancer have a risk for death from cardiovascular disease (CVD) in the year after diagnosis five times higher than men who receive surgery alone, a new study suggests.

The results were published online August 3 the Journal of Clinical Oncology.

"A small number of testicular cancer patients who received chemotherapy — about 11 in 6909 — died as a result of cardiovascular disease in the first year after diagnosis, a statistic that is noteworthy for many reasons, particularly because this type of cancer is usually curable and tends to afflict young men," said first author Chunkit Fung, MD, assistant professor at the University of Rochester Medical Center in New York.

However, "these findings should not affect decisions to use chemotherapy to treat testicular cancer when it is clinically appropriate," he emphasized in an interview with Medscape Medical News. "Every cancer treatment decision must be based on a balanced view of the risks and benefits."

For men 18 to 39 years of age, testicular cancer is both the most common and the most curable cancer. Since cisplatin-based chemotherapy was introduced in the 1970s, 10-year survival has improved to almost 95%, the researchers report.

Previous research conducted in Europe showed increased CVD risk in testicular cancer survivors who received chemotherapy, but many of these studies included only long-term survivors from the 1960s.

The study by Dr Fung's team was the first population-wide study to quantify CVD risk in patients with testicular cancer during, shortly after, and 2 decades after their treatment in the era when cisplatin-based therapy was used.

The researchers used data from the Surveillance, Epidemiology, and End Results (SEER) program on 15,006 patients with testicular nonseminoma who were treated from 1980 to 2010. Of this cohort, 6909 patients initially received chemotherapy and 8097 received surgery, all without initial radiotherapy. Average follow-up was shorter in the chemotherapy group than in the surgery group (8.7 vs 10.0 years).

Of the 429 deaths not related to cancer that occurred during the study period, 104 (24.2%) resulted from CVD (54 in the chemotherapy group and 50 in the surgery group).

There was a significant increase in the risk for CVD death in the chemotherapy group (standard mortality ratio [SMR], 1.36; 95% confidence interval [CI], 1.03 - 1.78), but not in the surgery group (SMR, 0.81; 95% CI, 0.60 - 1.07).

Of the 104 CVD deaths, 17 (16.3%) were caused by cerebrovascular disease (10 in the chemotherapy group and 7 in the surgery group). There was a significant increase in the risk for death caused by cerebrovascular disease in the chemotherapy group (SMR, 2.40; 95% CI, 1.15 - 4.42), but not in the surgery group (SMR, 1.07; 95% CI, 0.43 - 2.20). In the chemotherapy group, 5 of the 10 deaths occurred in the year after diagnosis.

It was only in the year after diagnosis that there was a significant increase in death after chemotherapy (SMR, 5.31 absolute excess risk [AER], 13.90). Causes of excess CVD death in the year after diagnosis included cerebrovascular disease (SMR, 21.72; AER, 7.43) and heart disease (SMR, 3.45; AER, 6.64).

There was no excess CVD death after chemotherapy in men who were more than 1 year out from their diagnosis, the researchers note.

Younger patients had a significantly increased risk for CVD death after chemotherapy (<30 years: SMR, 5.82; 30 - 39 years: SMR, 2.32). This increased risk in younger patients might be related to lower CVD risk in this age group, according to the researchers.

Independent risk factors for increased CVD death after chemotherapy for testicular cancer — after adjustment for time since testicular cancer diagnosis, age at diagnosis, calendar year of diagnosis, extent of disease, race, education level, and marital status — included being in the first year after diagnosis (hazard ratio [HR], 4.86; 95% CI, 1.25 - 32.08), distant disease (P < .05), and older age at diagnosis (P < .01).

Limitations of the study include a lack of information in the SEER database on general risk factors that could increase CVD risk (such as smoking and physical activity), type and doses of initial chemotherapy, and subsequent treatments.

More research will be needed about risk factors that could put testicular cancer patients at increased risk for rare cardiovascular complications, Dr Fung pointed out.

"Although our findings need to be confirmed, it is important that patients and oncologists recognize any type of potentially increased risk of death, even if it is quite rare, and apply evidence-based clinical practice guidelines for prevention and treatment of complications," he concluded.

Some of the authors report stock or other ownership, consulting or advisory roles, honoraria, and/or institutional research funding from GlaxoSmithKline, Janssen Scientific Affairs, Dendreon, Bayer, Astellas Pharma, and/or Accuray.

J Clin Oncol. Published online August 3, 2015. Abstract


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