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

Abstract

To provide new information on adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) after four cycles of etoposide and cisplatin (EPX4) or three or four cycles of bleomycin, etoposide, cisplatin (BEPX3/BEPX4). MethodsNine hundred fifty-two TCSs . 1 year postchemotherapy underwent physical examination and completed a questionnaire. Multinomial logistic regression estimated AHOs odds ratios (ORs) in relation to age, cumulative cisplatin and/or bleomycin dose, time since chemotherapy, sociodemographic factors, and health behaviors. ResultsMedian age at evaluation was 37 years; median time since chemotherapy was 4.3 years. Chemotherapy consisted largely of BEPX3 (38.2%), EPX4 (30.9%), and BEPX4 (17.9%). None, one to two, three to four, or five or more AHOs were reported by 20.4%, 42.0%, 25.1%, and 12.5% of TCSs, respectively. Median number after EPX4 or BEPX3 was two (range, zero to nine and zero to 11, respectively; P . .05) and two (range, zero to 10) after BEPX4. When comparing individual AHOs for EPX4 versus BEPX3, Raynaud phenomenon (11.6% v 21.4%; P , .01), peripheral neuropathy (29.2% v 21.4%; P = .02), and obesity (25.5% v 33.0%; P = .04) differed. Larger cumulative bleomycin doses (OR, 1.44 per 90,000 IU) were significantly associated with five or more AHOs. Increasing age was a significant risk factor for one to two, three to four, or five or more AHOs versus zero AHOs (OR, 1.22, 1.50, and 1.87 per 5 years, respectively; P , .01); vigorous physical activity was protective (OR, 0.62, 0.51, and 0.41, respectively; P , .05). Significant risk factors for three to four and five or more AHOs included current (OR, 3.05 and 3.73) or former (OR, 1.61 and 1.76) smoking (P , .05). Self-reported health was excellent/very good in 59.9% of TCSs but decreased as AHOs increased (P , .001). ConclusionNumbers of AHOs after EPX4 or BEPX3 appear similar, with median follow-up of 4.3 years. A healthy lifestyle was associated with reduced number of AHOs.

Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis

“…The study conducted by Igawa et al [50] showed that smoking history was a favorable predictor of efficacy of pemetrexed monotherapy in NSCLC, and long-term smoking history is associated with poor efficacy. After treatment with cisplatin, adverse outcomes of patients with testicular cancer were associated with smoking history [51]. Among patients receiving adjuvant chemotherapy, smoking reduced progression-free survival and overall survival in ovarian cancer [52].…”

Effects of high‐intensity aerobic interval training on cardiovascular disease risk in testicular cancer survivors: A phase 2 randomized controlled trial

“…Recent observational evidence in TCS treated with cisplatin 12 suggests that vigorous physical activity is protective against adverse health outcomes including CVD; however, to the best of our knowledge, no randomized evidence exists demonstrating the causal effects of aerobic exercise training on reducing CVD risks in TCS. The purpose of the High-Intensity Interval Training in Testicular cancer Survivors (HIITTS) trial was to evaluate the impact of HIIT on the established pathways of treatmentrelated CVD risk in TCS.…”

Treatment of refractory germ cell tumors in children with paclitaxel, ifosfamide, and carboplatin: A report from the Children's Oncology Group AGCT0521 study

“…Although relapsed germ cell tumors may continue to show responsiveness to cisplatin, its continued use is associated with significant short‐ and long‐term toxicities, including ototoxicity, neurotoxicity, nephrotoxicity, and, among adult men, a twofold increase in second malignant neoplasms and risk of cardiovascular disease; these late effects are particularly relevant in children and adolescents. The cisplatin analog carboplatin is effective in pediatric germ cell tumors with a better safety profile and fewer long‐term side effects.…”