Patients who received platinum-based chemotherapy or radiotherapy to treat testicular cancer had a significantly higher risk of dying from causes unrelated to their primary cancer, according to a study published in the Journal of Clinical Oncology.
In a population-based study, researchers sought to determine whether platinum-based chemotherapy and radiotherapy were the major risk factors for excess mortality among testicular cancer survivors.
The study included 5707 patients from the Cancer Registry of Norway who were diagnosed with testicular cancer from 1980 to 2009. The patients were treated with surgery alone (25%), platinum-based chemotherapy (44%), radiotherapy (27%), or chemotherapy plus radiotherapy (4%).
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The patients were followed for a median of 18.7 years. During that time, 665 patients (12%) died from causes unrelated to testicular cancer.
The overall non-testicular cancer mortality was significantly increased in the study cohort compared with the general population. The standardized mortality ratio (SMR) was 1.23, and the absolute excess risk (AER) was 11.14.
The highest non-testicular cancer mortality was observed in patients who were younger than 20 years of age at testicular cancer diagnosis (SMR, 2.27; AER, 14.42).
There was a significantly increased risk of non-testicular cancer death among patients who received chemotherapy (SMR, 1.23; AER, 7.68), radiotherapy (SMR, 1.28; AER, 19.55), and chemotherapy plus radiotherapy (SMR, 2.04; AER, 75.45) but not among patients who underwent surgery alone (SMR, 0.95; AER, -2.21).
Second cancer was “the most important cause of death” unrelated to testicular cancer, according to the researchers. The overall SMR for a second cancer was 1.53, and the AER was 7.94.
The risk of death from a second cancer was increased among patients who received chemotherapy (SMR, 1.43; AER, 4.25), radiotherapy (SMR, 1.59; AER, 13.38), and chemotherapy plus radiotherapy (SMR, 3.24; AER, 50.13) but not among those underwent surgery alone (SMR, 1.13; AER, 1.71).
Patients who received chemotherapy had a significantly increased risk of lung cancer (SMR, 1.69), leukemia (SMR, 3.26), esophageal cancer (SMR, 3.74), bladder cancer (SMR, 6.33), and cancers of the oral cavity and pharynx (SMR, 6.82).
Patients who received radiotherapy had a significantly increased risk of liver cancer (SMR, 3.02), stomach cancer (SMR, 3.15), cancers of the oral cavity and pharynx (SMR, 4.28), pancreatic cancer (SMR, 4.36), and bladder cancer (SMR, 4.91).
Patients who received chemotherapy plus radiotherapy had a significantly increased risk of stomach cancer (SMR, 12.85), pancreatic cancer (SMR, 6.86), and prostate cancer (SMR, 3.27).
When compared with surgery in a multivariable analysis, the overall risk of non-testicular cancer mortality was significantly increased with chemotherapy (hazard ratio [HR], 1.42), radiotherapy (HR, 1.94), and chemotherapy plus radiotherapy (HR, 3.27).
When compared with the general population, the patient cohort had an increased risk of non-cancer mortality (SMR, 1.15; AER, 4.71).
An analysis of the non-cancer causes of death revealed an excess of suicides in patients who received chemotherapy (SMR, 1.65) and an increased risk of death from diseases of the genitourinary system in patients who received chemotherapy (SMR, 3.29).
Radiotherapy was associated with an increased risk of death from diseases of the digestive system (SMR, 2.46), and chemotherapy plus radiotherapy was associated with an increased risk of death from certain heart diseases (SMR, 5.30).
The researchers concluded that platinum-based chemotherapy and radiotherapy are associated with an increased risk of non-testicular cancer mortality, and both health professionals and patients “should be aware of the risk of premature death.”
Reference
Hellesnes R, Myklebust TA, Fossa SD, et al. Testicular cancer in the cisplatin era: Causes of death and mortality rates in a population-based cohort. J Clin Oncol. Published online August 13, 2021. doi:10.1200/JCO.21.00637
