Oncofertility and oncosexualityvin non-Hodgkin lymphoma and testicular cancer survivors

Background – Recently great attention was brought on long-term consequences of antineoplastic treatments, with special focus to reproductive and sexual health. Human testis can be severely damaged by chemo and radiotherapy but, while literature offers plenty of data regarding common malignancies in reproductive age such as testicular cancer and Hodgkin lymphoma, we know little about other neoplasias. Similarly, knowledge of male sexological alterations in cancer derives mainly from prostate cancer, which can hardly be generalized to other pathologies. Since little is known about Non-Hodgkin Lymphoma survivors’ fertility and there is incomplete information for Testicular Cancer survivors sexological counselling, the aim of this work was: (Study 1) to evaluate semen quality and fertility status before and after treatments of patients who underwent semen cryopreservation after the diagnosis of NHL; (Study 2) to evaluate the effect of TC after orchiectomy and provide a complete follow up in order to highlight possible post treatment short and long-term sexological alterations. Material and Methods – Patients attending the Laboratory of Seminology – Sperm Bank “Loredana Gandini” for sperm cryopreservation were selected for both studies after a careful medical history collection. Exclusion criteria were any comorbidity and any other known factor interfering with sperm parameters. For Study 1, 224 patients (mean age 32.7 ± 8.6 years) with diagnosis of Non-Hodgkin Lymphoma were selected, and semen analysis was performed at baseline (T0) and at least one follow up visit at 12 (T1), 24 (T2) or more than 24 months (T3; median 52 months); fertility status was ascertained with a dedicated questionnaire. For Study 2, 241 sexually active consecutive patients (mean age 31.3 ± 6.9 years) with recent diagnosis of testicular cancer were selected. IIEF questionnaire was completed for sexual function evaluation at baseline post-orchiectomy (T0) and at least one follow up control at 6 (T1), 12 (T2), 18 (T3), 24 (T4), 48 months (T5) and after 5 years (T6, median 96 months) after chemotherapy; 223 healthy controls were also recruited for IIEF scores comparisons. Moreover, both TC patient and controls underwent blood hormones analysis (FSH, LH, total Testosterone). Results – Study 1 – Non-Hodgkin Lymphoma patients showed pre-therapy mean semen parameters within WHO 2010 normal range. Longitudinal post-therapy evaluation showed that sperm parameters significantly worsened at T1 compared to T0 (p < 0.001). Total sperm number at T2 remained significantly worse than T0 (p = 0.040) whereas it returned to values comparable to baseline at T3. Progressive motility and abnormal forms returned comparable to baseline at T2. 13.7% of survivors were azoospermic at T3. Permanent spermatogenesis impairment was associated with pelvic radiotherapy (OR 14.54, 95% CI 1.90 – 111.28) and treatment intensification for bone marrow transplant (33% azoospermia at T3). Regarding fertility, 14/22 pts who desired children were able to achieve fatherhood either through natural fertility (2 pts) or through ART (12 pts). Study 2 – Baseline prevalence of erectile dysfunction is 37.8% in TC pts vs 9.9% in healthy controls (p < 0.001). IIEF-15 baseline scores were significantly worse in TC group compared to controls (p < 0.001), with the exception of the orgasmic function domain (p = 0.334). Post-chemotherapy evaluation showed that erectile function improves significantly at T2 (T0 vs T2; p < 0.001) with further improvements at T3 and T4 compared to baseline (T0 vs T3: p = 0.014; T0 vs T4: p = 0.002). However, we detected an increase in erectile dysfunction prevalence at T5 with a significant reduction of erectile function domain scores, which seemed to persist at T6. Compared to controls, erectile function remains significantly worse at T1 then return comparable to healthy controls. Sexual desire, intercourse satisfaction and general satisfaction showed trends of improvement from baseline but remained significantly worse compared to controls for the whole duration of the study. No significant variation of the orgasmic function was detected against both baseline values and controls. The evaluation of sexual hormones revealed that prevalence of biochemical hypogonadism was 5.4% in the TC group. There were no hypogonadal patients in CTR group. Total testosterone in post-orchidectomy patients (T0) is significantly lower than controls (p < 0.001), but no significant variation was detected at T1 and T2. Finally, no significant correlation was detected between total testosterone levels and scores of any IIEF15 domain. Discussion – Study 1 demonstrates that Non-Hodgkin Lymphoma survivors undergoing intensive treatments and pelvic radiotherapy risk severe and permanent impairment of spermatogenesis. However, routine NHL chemotherapy regimens are compatible with spermatogenesis recovery after 2 years from the end of treatments and, while average sperm parameters may not fully return to pretreatment values, more than a half (63%) of patient who actively desire fatherhood can conceive either through natural conception or ART. Similarly, for Testicular Cancer survivors we confirm the presence of erectile dysfunction and impairment of sexual desire and satisfaction compared to a healthy population with improvements expected within one year from the end of the treatments. Absence of clear correlations with biochemical hypogonadism suggests that psychological burden following cancer diagnosis and treatments may play an important role. Information from these studies is of extreme importance since it will allow to increase the effectiveness of patients’ counseling interventions in an oncofertility service.