Longitudinal assessment of cognitive functioning in testicular germ cell tumor survivors.
Authors: Orszaghova Zuzana , Svetlovska Daniela , Vasilkova Lucia , Lesko Peter , Sycova-Mila Zuzana , Obertova Jana , Palacka Patrik , Rejlekova Katarina , Kalavska Katarina , Mladosievicova Beata , Mardiak Jozef , Mego Michal , Chovanec Michal 
Published: January 2024

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Background: Survivors of testicular germ cell tumors (GCT) may experience late toxicities derived from cancer treatment. Long-term cognitive impairment has been previously described in GCT survivors. This study aimed to prospectively perform a longitudinal assessment of cognitive functioning in GCT survivors. Methods: GCT survivors (N = 151) from National Cancer Institute in Slovakia completed the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) questionnaires during their annual follow-up visits. The study group consisted of survivors who completed at least four consecutive follow-up visits. The median of the 1st follow-up visit was 8 years (range 4-24). Survivors were treated with orchiectomy and active surveillance only (AS) (N = 21), cisplatin-based chemotherapy (CT) (N = 109), radiotherapy to the retroperitoneum (RT) (N = 11) or both chemotherapy and radiotherapy (CTRT) (N = 10). According to the received treatment, we longitudinally assessed cognitive scores in four cognitive domains: perceived cognitive impairment (CogPCI), quality of life affected by cognitive impairment (CogQoL), cognitive impairment perceived by others (CogOth) and perceived cognitive abilities (CogPCA), and overall cognitive function score. We also performed a subgroup analysis of survivors receiving cumulative doses < 400 mg/m2 (N = 48) and ≥ 400 mg/m2 (N = 70) of cisplatin. Results: Survivors treated with CTRT had persistently lower scores in CogPCA domain annually between the 1st and the 5th follow-up compared to AS group (all p < 0.05). CTRT group also had lower overall cognitive function scores compared to AS (all p < 0.03) in all follow-ups between the 2nd and the 5th follow-up visit. Survivors who received ≥ 400 mg/m2 of cisplatin had lower scores in CogPCA domain at the 1st and the 2nd follow-up visit compared to AS (mean score ± SEM: 21.56 ± 0.66 vs. 24.10 ± 0.63, p = 0.05, and 21.14 ± 0.59 vs. 23.76 ± 0.98, p = 0.014), lower overall cognitive function score at the 2nd follow-up compared to AS (110.66 ± 2.06 vs. 118.75 ± 2.66, p = 0.048), followed by a nonsignificant numerical trend of decline in CogPCA domain and overall cognitive score annually from the 3rd to the 5th follow-up. There was a nonsignificant numerical decline in all survivors annually between the 1st and the 4th follow-up in all cognitive domains and overall cognitive score. We observed a similar trend in all treatment groups separately. Conclusions: GCT survivors experience a long-term cognitive impairment that changes moderately over time. Survivors who received both chemotherapy and radiotherapy had the worst cognitive performance persisting at all follow-up visits. In addition, we observed a cognitive decline in survivors who received higher doses of cisplatin-based chemotherapy. To date, this is the first study that prospectively performed a longitudinal assessment of long-term cognitive functioning in GCT survivors.