Subsequent malignant neoplasms (SMNs) are one of the most serious and potentially lethal complications of cancer and its therapy. Radiotherapy has been known to be a human carcinogen, however, a growing body bolsters the selective contribution of chemotherapeutic agents to SMN risk. Cisplatin binds to and destructs DNA, hence producing partly reactive platinum in the serum and platinum–DNA adducts in human organs that are detectable up to 20 years after the completion of chemotherapy. In particular, any synergistic mechanistic effects of platinum with other carcinogens remain unclear.
In the study, bladder cancer accounted for the largest absolute excess risk (17.1%) of solid cancers. Other studies in testicular cancer survivors and childhood cancer have shown 1.9–8.0-fold increase in the risks of urological malignancies after cisplatin-based chemotherapy, including kidney and bladder cancers. The cisplatin primarily undergoes renal excretion in an extent that goes from short-term and long-term exposure of the genitourinary epithelium to urinary cisplatin that leads to an increased risk of bladder and kidney cancers that intrigue future analytical series, also any potential synergistic interactions between cisplatin and other carcinogens (for example, tobacco metabolites) in urological carcinogenesis.
The retrospective nature of data collection has several limitations in the study. Owing to lost data on platinum dose and body size in some patients, the investigators assessed the cumulative platinum dose on the basis of the number of chemotherapy cycles. Moreover, the information on the lifestyle factors is limited in the study that could have affected the SMNs risk, including tobacco use, alcohol consumption, and activity level. However, valuable information on platinum-associated cancers is provided. The testicular cancer is the most common cancer in young men and is largely curable. In addition, increased risk of solid cancers in survivors of childhood cancer is also linked to platinum-based chemotherapy that undermine the significance of continued follow-up monitoring of patients exposed to platinum.
Future studies should continue to assess the long-term effects of cisplatin-based chemotherapy on the temporal patterns and site-specific risk of SMNs, taking into consideration the influence of age at exposure, attained age, lifestyle factors, shared aetiological influences, and host determinants.