Long-Term and Late Effects of Germ Cell Testicular Cancer Treatment and Implications for Follow-Up

Abstract

Germ cell testicular cancer (TC) represents a malignancy with high cure rates. Since the introduction of cisplatin-based chemotherapy in the late 1970s, the 5-year survival rate has increased considerably, and it is currently above 95%. Because TC is usually diagnosed before the age of 40 years, these men can expect to live for another 40 to 50 years after being successfully treated. This success, however, is hampered by an increased risk of long-term and late effects of treatment. Secondary malignant neoplasms and cardiovascular disease represent the most common potentially life-threatening late effects, typically occurring more than 10 years after treatment. Other long-term effects include pulmonary toxicity, nephrotoxicity, neurotoxicity, decreased fertility, hypogonadism, and psychosocial problems. The incidence and time to onset of these various adverse effects vary according to treatment type and intensity. There is still little knowledge about underlying mechanisms and genetic susceptibility of the various adverse effects. Apart from treatment burden, it is not yet possible to identify patients who are at high risk for certain late effects after TC treatment. In this clinical review, we present the current status regarding different somatic and psychosocial long-term late effects after treatment for TC, based on Medline searches and our own research. Moreover, we postulate recommendations for general medical evaluations that should begin after treatment is completed and continue during follow-up.

Multi-Institutional Assessment of Adverse Health Outcomes Among North American Testicular Cancer Survivors After Modern Cisplatin-Based Chemotherapy

“…Retrograde ejaculation is the most common long-term complication after nerve-sparing postchemotherapy RPLND and can affect 11% to 29% of TCSs. 34 l The nonwhite population consisted of 11 (1.2%) black/African American, 44 (4.6%) Asian, one (0.1%) American Indian, 12 (1.3%) who identified more than one race, 61 (6.4%) other race, and six (0.6%) whose race was not stated. ) for cumulative cisplatin dose.…”

Long-term Relative Survival after Diagnosis of Testicular Germ Cell Tumor

“…The main cause is probably a continuous development of late effects of TGCT treatment, for which both direct and indirect mechanisms, such as the metabolic syndrome, have been suggested (1)(2)(3). Supporting this is the striking difference between RS curves of localized malignant melanoma and TGCT (Fig.…”

“…Despite today's excellent 10-year survival rates of above 95%, TGCT treatment is associated with an increased risk of potentially life-threatening late effects. The most important are second malignant neoplasms and cardiovascular disease, usually manifesting beyond 10 years of follow-up (1)(2)(3)(4)(5)(6)(7)(8). Even more alarming are the reports on increased mortality from these and other conditions in TGCT survivors (1-4, 9, 10).…”

The Sound of Silence: A Proxy for Platinum Toxicity

“…Importantly, long-term toxicities associated with the cumulative doses of cisplatin/etoposide include leukemia, second malignant neoplasm, CVD, and pulmonary problems, with the latter not being associated with bleomycin. 22,23 Pooling long-term toxicity data after three cycles of BEP and four cycles of EP for a metaanalysis of these outcomes might be worthwhile, especially because we have learned that extrapolation of acute toxicities is not always correct in the long term: less long-term neuropathy after chemotherapy with vinblastine as opposed to etoposide in combination with cisplatin and bleomycin was surprising, because vinblastine causes substantially more short-term paresthesia than etoposide. 6,24 Thereby, phase IV studies could help decision making in the absence of level I evidence.…”