Prospective Investigation on the Paternity Intention and Affecting Factors in 84 Post-treatment Testicular Cancer Patients Serkan Yenigurbuz1, Caner Ediz1, Yunus Emre Kizilkan1, Serkan Akan2, Mehmet Pehlivanoglu1, Muhammed Cihan Temel3, Hasan Huseyin Tavukcu1, Tuna Erturk4, Omer Yilmaz1 INTRODUCTION Testicular cancer is the most prevalent type of cancer in men aged 15–44 years in developed countries. (1) Low birth weight and a history of undescended tes- tis are established etiological factors of testicular can- cer along with sociocultural factors, including ethnicity, environmental exposure, family history, and inguinal hernia.(2,3) Testicular cancer is often detected at a young age, and there is a high treatment success rate, thanks to early diagnosis.(4) In patients with testicular cancer, fertility remains an important problem.(3,5-7) The post-treatment infertili- ty rate is as high as 30%.(8) Factors that affect semen parameters include patient's age, tumor type, treatment regimen, chemotherapy, radiotherapy, and retroperito- neal lymph node dissection.(9-13) Sperm cryopreserva- tion is routinely recommended to patients prior to the surgery due to the risk of organic-induced infertility.(14) Diagnosis and treatment of testicular cancer may im- pair the quality of life (QoL) of patients and create psy- chological stress along with infertility.(15) However, the paternity intention, which is considered secondary to cancer, is not adequately questioned, and thus, patients cannot be provided with routine psychosocial support in this regard. A study found that 51% of patients diag- nosed with testicular cancer had paternity intentions for the future, while 49% did not.(16) There are insufficient studies on paternity intention in patients with testicular cancer although many studies in the relevant literature have focused on organic-induced infertility based on semen analysis.(17-20) The present study intended to investigate the factors affecting post-treatment paternity intention in patients followed up after the diagnosis of testicular cancer and to make recommendations for the early postoperative period based on the identified factors. 1Department of Urology, Sultan 2. Abdulhamid Han Education and Research Hospital, Istanbul, Turkey. 2Department of Urology, Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey. 3Department of Urology, Nevsehir State Hospital, Nevsehir, Turkey. 4Department of Anesthesiology and Reanimation, Sultan 2. Abdulhamid Han Education and Research Hospital, Istanbul, Turkey. *Correspondence: Sultan Abdulhamid Han Education and Research Hospital, Istanbul, Turkey. Tibbiye cad. Selimiye mah. Uskudar/ISTANBUL Tel: +90 553 453 34 27. Fax: +90 216 542 20 20 . E-mail: yunusemrekizilkan@gmail.com. Received June 2022 & Accepted January 2023 Purpose: to investigate the factors affecting post-treatment paternity intention in patients followed up after the diagnosis of testicular cancer and to make recommendations for the early postoperative period based on the iden- tified factors. Materials and Methods: This prospective descriptive study included a total of 185 patients who presented to our outpatient clinic between February 2000 and July 2020 who had radical orchiectomy due to suspected testicular cancer based on physical examination and other assessments. Contact information was found for 88 of 185 pa- tients, and accordingly, the patients were reached by one-to-one phone calls. Upon literature review, a question- naire consisting of 10 previously validated items was developed by the researchers. The patients were compared by separating them into two groups composed of patients with (Group 1) and without (Group 2) paternity intention. Results: A total of 84 patients participated in the study, and the participation rate was 95.5%. It was found that 19 of 32 (38%) patients with paternity intention already had children. Only 21 (40%) of 52 patients without paternity intention were married. The mean age was 26.65 (18–39) years in Group 1, while it was 28.73 (19–45) years in Group 2. Tumor volume and serum tumor markers were higher in Group 2 than in Group 1. Parameters such as testicular side in which the tumor was located, smoking status, undescended testis history, and postsurgical chemo- therapy history were not statistically significant difference between the two groups. Conclusion: The major findings included that the young aged, unmarried, and serious testicular cancer (Tumor volume and serum tumor markers were higher) can be affecting factors for testicular cancer patients’ paternity intention. Early psychological counseling about paternity may be useful for testicular cancer patients. Keywords: cancer; fatherhood; infertility; testis; testicular cancer Urology Journal/Vol 20 No. 3/ May-June 2023/ pp. 181-186. [DOI:10.22037/uj.v20i.7337] ANDROLOGY MATERIALS AND METHODS Study Design This prospective descriptive study was approved by the local Ethics Committee and was conducted pursu- ant to the principles of the World Medical Association Declaration of Helsinki's Ethical Principles for Medical Research Involving Human Subjects (HBAEK:20/415). Participants The study included patients who presented to our out- patient clinic between February 2000 and July 2020 with complaints of testicular swelling or mass and for whom a radical orchiectomy decision was made due to suspected testicular cancer based on physical examina- tion and other assessments. Patients who were not diag- nosed with testicular cancer upon the pathology results were excluded from the study. A total of 185 patients meeting the criteria were included in the study. Con- tact information was found for 88 of 185 patients, and accordingly, the patients were reached by one-to-one phone calls. All the patients confirmed that their partner was not infertile. Only one patient declined to partici- pate in the study. The interview could not be realized with one of the patients, because of death. In addition, two patients were excluded due to bilateral orchiecto- my. The remaining 84 patients with testicular cancer were included in the study. Data Collection Upon literature review, a questionnaire consisting of 10 previously validated items was developed by the researchers. Study data were collected over the phone based on the patients’ responses for the questionnaire items, including the education status, comorbid diseas- es, smoking status, additional treatment status after the surgery, number of children, follow-up periods, paterni- ty status, treatment choices for infertility, and if any of their male children were diagnosed with undescended testis. Upon collection of the data, the participants were classi- fied into two groups composed of patients with (Group 1) and without (Group 2) paternity intention. Patients with paternity intention were further divided into two subgroups based on having (Group 1a) and not having (Group 1b) children. Patients without paternity inten- tion were also divided into two subgroups as married (Group 2a) and not married (Group 2b). Letter 242 Paternity Intention in Post-Treatment Testicular Canver Patients-Yenigurbuz et al. Table 1. Baseline characteristics of enrolled patients Variable Group 1 Group 2 P-value Age (year)(IQR) 26.65 (9,25) 28.73 (10,5) .199 Education status Under high school 18.8% 26.9% .006* High school and above 81.2% 73.1% Smoking status Smoker 12 15 .410 Non smoker 20 37 Tumour Volume (cc) 37.5 (26,25) 43.1 (31,5) .478 AFP (ng/mL) 221 (215,7) 1455 (312,75) .418 β-HCG (mlU/mL) 99 (25,23) 3144 (44,05) .677 LDH (U/L) 371(198,5) 541(278) .078 Abbreviations: IQR, Interquartile Range; cc, Cubic Centimeter; ng/mL, nanogram / milliliter; mlU/mL, mililiter unit/mililiter; U/L, unit/ liter. Figure 1. Flow Chart for patients' enrollment Vol 20 No 3 May-June 2023 182 Andrology 183 Statistical Analysis SPSS for Windows version 22.00 was used for the sta- tistical analyses. Shapiro–Wilk test and Q-Q plot were used to determine normal data distribution. All the var- iables were non-normally distributed. Quantitative var- iables were expressed as median (interquartile range). Qualitative variables were expressed as frequency and percentage, and a Chi-square test was applied and no expected cell count was less than 1 and at most 20% of expected cell counts were less than 5. Mann–Whit- ney's U-test was used to evaluate all the non-normally distributed variables. A p value of <.05 was considered statistically significant in all analyses. RESULTS In this study, 88 patients were contacted over phone. A total of 84 patients participated in the study, and the participation rate was 95.5%. It was found that 19 of 32 (38%) patients with paternity intention already had children. Only 21 (40%) of 52 patients without paterni- ty intention were married. The data are presented in the flowchart (Figure 1). The patients were compared by separating them into two groups composed of patients with (Group 1) and without (Group 2) paternity intention. The mean age was 26.65 (18–39) years in Group 1, while it was 28.73 (19–45) years in Group 2. In Groups 1 and 2, the rates of high school and higher education were 81.2% and 73.1%, respectively, and it was higher in the group with paternity intention than in the group without such an intention (P = .006). While 37.5% of the patients in Group 1 were smokers, this rate was 28.8% in Group 2. An investigation of history of undescended testis and smoking data indicated that there was no statistically significant difference between the two groups (P = .409 and P = .41, respectively). Tumor volume and serum tumor markers were higher in Group 2 than in Group 1, but the difference was not statistically significant (Ta- ble 1). Parameters such as testicular side in which the tumor was located, smoking status, undescended testis history, and postsurgical chemotherapy history were not statis- tically significant difference between the two groups. In addition, there was no effect of lymph node positivity in retroperitoneal, thorax, or both regions on the pater- nity intention in terms of the presence of lymph nodes (Table 2). A comparison of the subgroups with and without chil- dren in Group 1 indicated that the use of food supple- ments was similar in both subgroups. However, the patients not having children applied to assisted repro- ductive techniques significantly more often than the other subgroup (P = .006) (Table 3). While the mean time from treatment to paternity in- tention was 23 months (IQR:36) in the subgroup with children, this duration was 29 months (IQR:48) in the subgroup without children. Furthermore, pregnancy was achieved after an average of 7.6 months of unpro- tected sexual intercourse. The postoperative follow-up periods of the patients were 65.4 (IQR:64,4) and 72.6 (IQR:67,6) months in Groups 1 and 2, respectively, and there was no significant difference between the two groups (P = .467). An investigation of the patients’ pathology specimens showed that 7 patients out of 32 with paternity intention were diagnosed with seminoma and 25 with non-sem- inoma testicular cancer. On the other hand, 18 patients out of 52 without paternity intention were diagnosed with seminoma and 34 with non-seminoma testicular cancer. The pathology results did not have any effect on the paternity intention upon comparative analysis between the two groups (P = .215). DISCUSSION Testicular cancer generally occurs during the peak re- productive years of men, which coincides with career and family planning. The paternity intention and the success of fertilization in disease management vary depending on the administered treatments and the psy- chosocial effects of the disease. In the present study, 38.09% (n = 32) of the patients who were followed up after testicular cancer diagnosis stated their paternity in- tention following the diagnosis. Similarly, in a study by Spermon et al., paternity intention was stated by 43% of the subjects(13), whereas Uçar et al. reported the rate as 30%.(12) It is noteworthy that although the rates of paternity intention are at comparable levels, they tend to be below 50%. The young age of the population and the possible low level of marriage may account for these rates.(21) However, a study conducted in Norway published results inconsistent with the aforementioned reasoning. The likelihood of marriage among men diag- nosed with cancer was 5% higher than that in men with- out cancer diagnosis (OR = 1.05, %95 CI: 1.01–1.11). According to the above study, the rates were signifi- cantly higher, especially after testicular cancer (OR = 1.11). Marriage after cancer diagnosis is more common today than it used to be, and there are minor general differences in the marriage rates of cured individuals compared to the population not diagnosed with cancer. Nevertheless, testicular cancer in men is associated with increased marriage rates.(22) According to a study conducted in Turkey, 82.5% of patients diagnosed with cancer obtain information about their disease from a doctor. Moreover, 45.8% of the patients stated that communication with healthcare professionals was partially sufficient, 35.0% as insuffi- cient, and 19.2% as sufficient. Additionally, 63.3% of the patients requested better communication with their Variable Group 1 Group 2 P-value Testicular side Right 16 29 .607 Left 16 23 Smoking status (-) 20 37 .410 (+) 12 15 Undescended testis (-) 27 47 .495 (+) 5 5 Chemotherapy (-) 10 12 .408 (+) 22 40 Retroperitoneal LN (-) 15 26 .781 (+) 17 26 Thorax LN (-) 27 45 .761 (+) 5 7 Retro + Torax LN (-) 27 45 .761 (+) 5 7 Abbreviations: LN, lymph node. Chi-square test was used. p < .05 was accepted as the degree of significance. (n = 84) Table 2. Statistical comparison of the factors in the questionnaire that affect paternity desire in both groups. Paternity Intention in Post-Treatment Testicular Canver Patients-Yenigurbuz et al. doctor. While 65.8% of the patients expected emotional support, 75% wanted to learn about the effects of the disease on their psychological state.(23) Another study found a high level of psychological morbidity in both patients and their relatives, even 5 years after diagnosis, despite an excellent prognosis in patients with testicular cancer.(24) It is advisable to start educational activities about the disease immediately after the diagnosis of tes- ticular cancer, especially in case of patients with low educational status. At this point, patient associations can play an active role as regards psychosocial support for the disease. Recently, the web-based Kanker Na- zorg Wijzer (Guidelines for Post-Cancer Care) was de- veloped in the Netherlands to provide cancer survivors with psychosocial and lifestyle support. Although such a support is not available for patients with testicular cancer, it can be used to that end in the future.(25) Although there is no clear correlation between testic- ular cancer treatment and biochemical hypogonadism, it may be suggested that sexual aversion and dysfunc- tion may be substantially associated with psychological factors, including testicular cosmetic deficiency due to orchiectomy, chronic pain, or anxiety, fear, and mood disorders caused by cancer diagnosis.(26,27) In addition, major surgical interventions such as retroperitoneal lymph node dissection, which can lead to ejaculation and/or orgasm disorders in patients with testicular can- cer, may give rise to such problems.(28) Physical and psychological changes in these patients also adversely affect their perspectives on business and general life and career decisions.(25) Although not addressed during the telephonic interviews with the patients, these unex- pected changes may be effective in paternity intention. Education is another possible factor that decides the paternity intention in patients with testicular cancer.(30) The intention to have a child was higher in patients with testicular cancer with a higher educational status. The higher values of both tumor volume and tumor markers in Group 2 patients with a lower high school or high- er education level may be associated with presenting late to a physician. The high success rate in testicular cancer is associated with early diagnosis. As the diag- nosis period is delayed, the requirement for additional treatments increases. Gonadotoxic treatments lead to an overall reduction in male fertility by 30%, and there is currently no method available to predict which patients would become azoospermic following the treatment. The possible size difference in the palpable mass as a result of late diagnosis may also explain the lower pa- ternity intention compared to the other group because of the fact that the patients are psychosocially more affect- ed. Along with paternity intention, patients with larger, more invasive tumors are at risk for infertility due to local tumor effects.(29) The effects of late diagnosis in this patient group should be evaluated in further detail as regards both the paternity intention and infertility. Chemotherapeutic agents constitute another aspect in the treatment of testicular tumor, which should be considered carefully in terms of both their effects and side effects. In the present study, there was no effect of adjuvant chemotherapy following orchiectomy on paternity intention, which was consistent with the rel- evant literature.(30) The patients became fathers after an average of 30 months after treatment in the present study, while the European Society of Medical Oncolo- gy recommends postponing pregnancy for at least 12 months after chemotherapy to avoid teratogenic effects. (31,32) Uçak et al. suggested in their study that this pe- riod was 3 years(30), whereas Spermon et al. reported that the patients became fathers within 1 year after the treatment.(33) Although the results are heterogeneous, it is noteworthy that the patients complied with the rec- ommendations. It is important to know how sociocultural differences in sexuality, masculinity, and fertility affect the survi- vors to better understand the impact of testicular cancer on the QoL. Although QoL distinctively deteriorates at diagnosis and throughout the treatment, it later returns to normal levels defined by matched controls. Never- theless, there are several chronic conditions associated with the diagnosis and treatment of testicular cancer that plague the survivors and affect their QoL, includ- ing anxiety, sexuality, and fertility. Even if these issues have no impact on QoL measurements, they have an impact on QoL.(21) As expected, the rate of use of supplemental food and assisted reproductive techniques was higher in patients with testicular cancer who had paternity intention but did not have a child when compared with the other group. This information reflects the desire of patients with testicular cancer who have fertility problems to access supportive treatments in case of a paternity in- tention. Therefore, the first problem to be addressed is the elimination of negative thoughts that psychosocially lead to paternity desire. Early introduction of supportive treatments against misconceptions should be discussed frequently by urologic oncologists and andrologists. A review published in 2019 reported that clear guidelines on fertility counseling for patients with cancer in the context of fertility preservation, which removes ambi- guity as regards who conducts the counseling, what the counseling covers, and what level of psychosocial sup- port can be most effective, might be helpful.(21) Early assessment of this patient group by psychiatrists and/ or clinical psychologists through a multidisciplinary ap- proach might be the “next step” in the management of patients with testicular cancer. This study suffers from the following limitations. Al- though more patients could have been included in our retrospective archive-based study, the number of partic- Variable Group 1a Group 1b P-value Supplementary food (-) 18 10 .135 (+) 1 3 Assisted reproductive techniques (-) 15 4 .006* (+) 4 9 Table 3. The effect of using assisted reproductive techniques and supplementary food on having a child in those with a desire for paternity Crosstab analysis was used. p < .05 was accepted as the degree of significance. (n = 32) Paternity Intention in Post-Treatment Testicular Canver Patients-Yenigurbuz et al. Vol 20 No 3 May-June 2023 184 Andrology 185 ipants was lower than anticipated because of the fact that there were patients whose data could not be accessed. Furthermore, the contact information of certain patients had changed. Owing to the COVID-19 pandemic, face- to-face interviews aimed to inform patients about pa- ternity in psychosocial terms could not be conducted during the diagnosis and treatment. Another important point is that collecting patients' answers through phone call might be interfered by subjective thoughts of the authors. In addition, the lack of an age-matched control group can be considered as one of the limitations of the present study. CONCLUSIONS While studies in the relevant literature on testicular cancer and fertility have often focused on semen pa- rameters, low educational status was found to be a fac- tor that might negatively affect the paternity intentions in our study. Psychosocial counseling, which can be commenced immediately after the diagnosis, can play an important role in this regard and cover many factors that may negatively affect the QoL and the paternity intention. Early diagnosis should be reinforced by early psychological counseling. ACKNOWLEDGEMENT The authors would like to thank urology and pathology department of hospital for the preparing of this manu- script. CONFLICT OF INTEREST The authors report no conflict of interest. This research received no specific grant from any funding agency in the public, commercial, or not for profit sectors. REFERENCES 1. Znaor A, Lortet-Tieulent J, Jemal A, Bray F. International variations and trends in testicular cancer incidence and mortality. 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