Platinum retention in plasma, urine, and normal colonic mucosa in cisplatin-treated testicular cancer survivors.

Abstract

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have increased cancer risk. Platinum retention in healthy tissue may contribute to carcinogenesis. We assessed total platinum concentrations in plasma, urine, and normal colonic mucosa samples in TCS treated with cisplatin. From the total TCS treated with ≥3 cycles cisplatin who participated in a colonoscopy-screening study in four Dutch hospitals (n = 154), plasma (n = 131) and urine (n = 115) samples were collected. During colonoscopy, 60 biopsies of normal colonic mucosa (two samples each per 30 randomly selected patients undergoing colonoscopy) were obtained. Samples were analyzed for total platinum concentrations using inductively coupled plasma mass spectrometry and compared with controls (plasma: 10, urine: 3, normal colonic mucosa: 9). The median age at colonoscopy was 50 years (interquartile range (IQR): 43-57) and the median time since treatment was 20 years (IQR:16-26). Median platinum concentrations in plasma (38 pg/mL; IQR: 24-61 pg/mL) and urine (376 pg/mL; IQR: 208-698 pg/mL) remained elevated in TCS up to 40 years post-treatment and were higher than in controls (all controls were below limits of detection [plasma: 25 pg/mL, urine: 6 pg/mL]). The median platinum concentration in normal colonic mucosa was 0.58 pg/mg (IQR: 0.33-1.59 pg/mg) in the transverse and 0.51 pg/mg (IQR:0.26-1.25 pg/mg) in the descending colon. Cisplatin treatment is associated with long-term retention of platinum in various patient sample types. This might increase cancer risk by causing somatic mutations, potentially explaining the elevated risk of second malignant neoplasms in TCS. The long-term effects of platinum retention should be monitored to understand carcinogenesis and to provide guidelines for early second cancer detection. Trial registration: ClinicalTrials.Gov: NCT04180033.