Persistence of platinum in semen of cisplatin-treated survivors of advanced testicular cancer.

5056 Background: Cisplatin is highly curative treatment for testicular cancer. Most survivors develop azoospermia immediately after cisplatin with recovery expected in 50% at 2 years and 80% at 5 years. Platinum is a heavy metal that can be detected at low levels in serum many years after treatment, however, it is not known whether platinum also persists in semen and if platinum persistence in semen is associated with impaired fertility. Methods: Testicular cancer survivors previously treated with cisplatin were enrolled, relapsed disease treated with salvage chemotherapy was excluded. Semen samples were collected to assess semen quality. Repeat semen collections were performed if azoo- or oligospermia was noted. Serum and semen Platinum levels were determined using HPLC-tandem mass spectrometry. DNA Fragmentation Index (DFI) was measured. Results: From 11/2017 to 12/2019, 38 pts (median age 32 years; range: 19-52; median BSA 2.03; range: 1.81-2.61) were enrolled, 31 were treated with 3 cycles of Bleomycin, Etoposide, Cisplatin. Median cumulative cisplatin dose was 300 mg/m2 (range: 274-404). Median serum platinum concentration was 0.1 ng/mL (range: 0-22.6) at a median of 11 months (range 0.5-36) post treatment completion. Median semen platinum concentration was 0.5 ng/mL (range: 0.2-28.7) at a median of 14 months (range: 1.3-40) post treatment completion. Semen platinum levels were higher in semen than in blood drawn at the same time (p = 0.03). Semen platinum levels were associated with time from last cisplatin dosing (r = -0.34; p = 0.09) but not cumulative cisplatin dose (r = -0.10, p = 0.63). Sperm concentration was correlated with time from last cisplatin dosing (r = 0.58, p < 0.001) but not with semen platinum level (r = -0.15, p = 0.46). DFI was associated with time from last cisplatin dosing (r = 0.55, p = 0.08) but not with semen platinum level (r = -0.32, p = 0.33). In 4 pts with serial semen samples available, semen platinum level decreased with time, sperm concentration and motility increased. Conclusions: Platinum can be detected in semen in long-term testicular cancer survivors at higher levels than matched blood samples. Our preliminary findings may have important implications for reproductive health of survivors of advanced testicular cancer, further studies are needed to assess the relationship between platinum persistence in semen and recovery of fertility post chemotherapy.

Persistence of platinum in semen of cisplatin-treated survivors of advanced testicular cancer.

519 Background: Even in patients (pts) with widely metastatic germ cell tumors cure rates are high with cisplatin based chemotherapy. Survivors of testicular cancer often have impaired gonadal function possibly related to chemotherapy. Most pts develop temporary azoospermia with recovery in about 50% after 2 years and 80% after 5 years. Platinum persists in blood in these pts, however, it is not known whether platinum also persists in semen. Methods: Pts who completed cisplatin > 3 months previously were enrolled. Age, total cisplatin dose and date of completion of treatment were collected. A semen sample was collected from each patient for analysis to assess semen quality. A blood sample was collected to assess FSH/LH/testosterone/creatinine. Serum and semen platinum levels were measured using HPLC-tandem mass spectrometry. Results: Between 11/2017 and 09/2018, 9 pts (median age 32 years; range: 18-52) were enrolled to the study, all were treated with standard Bleomycin, Etoposide, Cisplatin regimen. Blood samples were collected from 7 pts, and semen samples from 4 pts. Median total cisplatin dose given was 658 mg (range: 570-780). Median serum platinum concentration was 0.395 ng/mL (range: 0.10-0.94) at a median of 10 months (range 4.5-13) post completion of treatment. Median semen platinum concentration was 1.06 ng/mL (range: 0.25-1.47) at a median of 10 months (range: 6-14) post completion of treatment. Semen platinum levels were associated with total cisplatin dose administered (Pearson correlation, r = 0.645) and time from completion of treatment (Pearson correlation, r = 0.386). In all 4 pts with matched samples, the semen platinum level was higher than the serum platinum level. Semen analysis showed 2 pts were azoospermic post treatment, 1 of these was also azoospermic prior to treatment; 1 pt had normal semen analysis post treatment and 1 had a low sperm count post treatment. Conclusions: This is the first study demonstrating that platinum persists in semen > 6 months post completion of cisplatin-containing chemotherapy. Platinum levels are higher in semen than in blood following treatment. Our preliminary findings may have important implications for reproductive health of survivors of advanced testicular cancer.