Unilateral Testicular Cancer Research Articles

Efficacy and Safety of Testosterone Replacement in Testicular Cancer Survivors With Treatment-Influenced Hypogonadism: A Systematic Review.

The objective is to evaluate the efficacy and safety of testosterone supplementation in testicular cancer survivors with treatment-related hypogonadism. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and used Embase, PubMed/MEDLINE, Cochrane Central, Web of Science Core Collection, Korean Journal Index, SciELO, and Global Index Medicus to obtain data in June of 2024. Analyses evaluating testosterone supplementation in testicular cancer survivors with treatment-induced hypogonadism were included. Any analyses not assessing supplementation in this population or deemed unretrievable were excluded. Ten analyses were included for analysis. A total of 332 bilateral or unilateral testicular cancer survivors with treatment-influenced hypogonadism were reviewed, with 238 patients receiving testosterone replacement. Eight of the 10 analyses assessed participants without poor quality-of-life (QOL) metrics, metabolic factors, and bone mineral density (BMD) at baseline and only found a significant benefit in fat distribution metrics with testosterone supplementation. Two analyses evaluated participants with poor QOL metrics or BMD at baseline and showed improvements in QOL or BMD with testosterone supplementation. There is robust evidence regarding the efficacy and safety of testosterone replacement in hypogonadal individuals but limited evidence specifically evaluating supplementation in testicular cancer survivors with treatment-influenced hypogonadism. The results suggest testosterone replacement may be beneficial in patients with impaired QOL metrics, metabolic factors, and BMD at baseline; the results also suggest that routine supplementation for all individuals in this patient population lacks efficacy.

Oncological treatments have limited effects on the fertility prognosis in testicular cancer: A systematic review and meta-analysis.

Testicular cancer is the most common solid tumour among young men in the reproductive phase. After completing cancer treatment, up to 77% of cancer survivors report an interest in paternity after completing cancer treatment. To preserve fertility, most guidelines recommend that physicians should counsel their patients about sperm cryopreservation before initiating gonadotoxic therapy. However, few studies have assessed fertility parameters after testicular cancer therapies over the last 20 years. To close the gap of data regarding gonadotoxicity of testicular cancer therapies to enable more accurate counselling regarding fertility preservation. A systematic literature search was conducted in Medline, Embase and Cochrane until December 2022. The systematic review included studies of men who had undergone all types of unilateral testicular cancer treatment, whereas the meta-analysis excluded studies with unspecified treatments, less than 10 patients for outcome evaluation or rare tumours. Infertility (i.e. azoospermia, failure to achieve paternity or the usage of cryosperm) was defined as outcome. The qualitative analysis included 30 studies with a total of 13,718 men after unilateral testicular cancer. Treatment comprised active surveillance after unilateral orchidectomy (32.7%), radiotherapy (23.1%), standard- or low-dose chemotherapy (33.7%) and high-dose chemotherapy (1.4%). Post-treatment spermiograms were analysed in 17 studies. The quantitative synthesis included 23 studies, revealing an overall pooled prevalence of infertility (95% CI) of 14% (9%-21%). Azoospermia occurred in 8% (6%-12%). For good-prognosis patients who received standard therapy, the overall prevalence of infertility was only 4% (2%-10%). So far, this very first meta-analysis of overall infertility prevalence provides the best approximation of fertility prognosis for men who have undergone testicular cancer therapy. Despite the low prevalence of infertility, it is still recommended to undergo sperm cryopreservation because of the uncertainty of the subsequent therapy and the lack of large longitudinal data on individual treatment effects.

O-311 Oncological treatments have limited effects on the fertility prognosis in testicular cancer: A systematic review and meta-analysis

Abstract Study question What is the prevalence of infertility defined by azoospermia, failure to achieve paternity or the usage of cryosperm after oncological treatments in testicular cancer? Summary answer The overall prevalence of infertility (95% CI) is 14% (9-21%) after all therapy types and 4% (2-10%) in a pooled subgroup of good-prognosis patients. What is known already Testicular cancer is the most common solid tumor among young men in the reproductive phase between 15 and 45 years. More than 95% of the patients become long-term survivors and up to 77% of cancer survivors report an interest in paternity after completing cancer treatment. Most guidelines recommend that physicians should counsel their patients about sperm cryopreservation before initiating gonadotoxic therapy. However, few studies have assessed fertility parameters after testicular cancer therapies over the last twenty years. Thus, this very first meta-analysis in a large pooled study population of patients functions as the best approximation of fertility prognosis so far. Study design, size, duration The systematic review and meta-analysis is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. It was performed on all published studies since 2000 that have reported the prevalence of azoospermia, the failure to achieve a pregnancy over 12 months of regular unprotected sexual intercourse or the usage of cryosperm after oncological treatments of unilateral testicular cancer. Participants/materials, setting, methods A systematic literature search was conducted in Medline, Embase and Cochrane in December 2022. For the systematic review, studies with men after all types of unilateral testicular cancer were included. For the meta-analysis, studies with unspecified treatments, < 10 patients for outcome evaluation or rare tumours were excluded. Infertility was defined as azoospermia, failure to achieve paternity or the usage of cryosperm. The quality of the individual studies was assessed using the Newcastle-Ottawa Scale. Main results and the role of chance A total of 126 studies remained following screening of the abstracts and fulltext for the subject of the study. Of these, 30 studies including 13718 men with a history of unilateral testicular cancer were eligible and analysed for qualitative synthesis. Sample sizes ranged from 17 to 4846 patients with a follow-up from 1-30 (mean 6.5) years. Histology included seminomas (43.9%), non-seminomas (49.6%) and sex cord or stromal tumors (0.01%). Treatment comprised active surveillance after unilateral orchidectomy (32.7%), radiotherapy (23.1%), standard or low-dose chemotherapy (33.7%) and high-dose chemotherapy (1.4%). Spermiograms after treatment were analysed in 17 studies. A quantitative synthesis was performed in 23 studies. To account for heterogeneity observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The overall pooled prevalence of infertility (95% CI) in men with unilateral testicular cancer after standard oncological treatment was 14% (9-21%). Azoospermia after all types of oncological treatments appeared in 8% (6-12%) of the pooled study population. For good-prognosis patients who received standard therapy (i.e. surgery with or without retroperitoneal lymph node dissection, low- or standard dosed platin-based chemotherapy up to four cycles and / or radiotherapy), the overall prevalence of infertility was only 4% (2-10%). Limitations, reasons for caution First, the majority of the studies based on either questionnaire or register data with evident selection bias. Second, further subgroup analysis was impossible due to predominantly mixed treatment cohorts allowing only an approximation of standard therapy effects. Third, infertility might have occurred due to factors besides the oncological therapy. Wider implications of the findings Our meta-analysis includes all men with fertility outcome after testicular cancer therapy. Despite the overall low prevalence of infertility, sperm cryopreservation should still be recommended since it is unclear which therapy will follow after surgery and since there is no large longitudinal data for the various individual treatment effects. Trial registration number PROSPERO (Registry number CRD42023384057)

Thyroid hypofunction in aging testicular cancer survivors

Purpose Thyroid hypofunction is a late effect observed in several groups of cancer survivors, but has to date not been evaluated in-depth in testicular cancer survivors (TCSs). We investigated the prevalence of thyroid hypofunction in long-term TCSs and compared the findings with those of a comparison group from the general population. Patients and Methods Norwegian TCSs diagnosed with unilateral testicular cancer in the period 1980–1994 (N = 1,436) were grouped according to their cancer treatment (Surgery only; Radiotherapy only; Cisplatin-based chemotherapy, eventually combined with radiotherapy). They were invited to participate in three surveys covering up to three decades post-diagnosis. Serum thyrotropin (s-TSH) from samples collected from the last survey were analyzed. S-TSH results were also available from a health survey of the general population performed in a county in mid-Norway (the HUNT3 Survey [comparison group]). Data on the prescription of thyroid hormone replacement therapy (levothyroxine) from the Norwegian Prescription Database were obtained for the TCSs and the comparison group’s participants. Thyroid hypofunction was defined as ‘untreated’ (overt or subclinical) hypothyroidism (with s-TSH ≥3.5 mIU/L and no regular prescription of levothyroxine) or ‘treated’ hypothyroidism with regular prescription of levothyroxine. Results Three decades after diagnosis the prevalence of thyroid hypofunction (i.e., both treated and untreated) was 11% in the TCSs and the prevalence ratio was 1.9 indicating an almost doubled prevalence in the TCSs compared to the comparison group (prevalence ratio 1.91, 95% CI [1.54; 2.38]). However, there were no significant differences in the risk of thyroid hypofunction related to the TCSs’ treatment modality. Conclusion TCSs may have an increased prevalence of thyroid hypofunction compared to the general population. Hypothyroidism has negative consequences related both to primary hypogonadism and to cardiovascular disease. As both conditions are overrepresented in TCSs, regular monitoring of thyroid hormones may be advisable.

Sexual Function and Quality of Life in a National Cohort of Survivors of Bilateral Testicular Cancer

BackgroundSexual function and quality of life remain unexplored among long-term survivors of bilateral testicular cancer (TC). ObjectiveTo investigate sexual function, fatigue, anxiety, and depression among long-term survivors of bilateral TC (unilateral TC with contralateral germ cell neoplasia in situ [TC+GCNIS] or bilateral TC [BTC]). Design, setting, and participantsThis was a cross-sectional study of 2479 long-term TC survivors, of whom 126 were treated with contralateral radiotherapy for GCNIS, 93 were treated with bilateral orchiectomy for BTC, and 2260 had unilateral TC (reference group). Outcome measurements and statistical analysisOutcomes were assessed using validated questionnaires at a median time since diagnosis of 17 yr (interquartile range 12–23). Results for survivors of TC+GCNIS and of BTC were compared with those for the reference group. Adjustment was made for age and treatment for disseminated disease. Results and limitationsThe age-adjusted risk of anxiety was significantly higher among BTC survivors (odds ratio 1.7, 95% confidence interval [CI] 1.1–2.8; p=0.002) than in the reference group. Apart from a higher risk of reduced motivation among survivors of TC+GCNIS (β=0.067, 95% CI 0.0013–0.13; p=0.046) there were no significant differences between the groups. Limitations include the low number of cases with symptoms of depression. ConclusionsSurvivors of BTC had a higher risk of anxiety but did not experience impairment of other aspects of quality of life when compared to survivors of unilateral TC. These results are of importance for evidence-based information on late effects for bilateral TC patients. Patient summaryWe evaluated quality of life and sexual function among long-term survivors of bilateral testicular cancer. Reassuringly, we did not find impaired quality of life apart from a higher risk of anxiety when comparing survivors of bilateral testicular cancer with survivors of unilateral testicular cancer.

Vitamin D status among long-term survivors of testicular cancer.

A correlation between disturbances in hormone levels and the onset of metabolic disorders has been reported in long-term survivors of testicular cancer (TC).We evaluated serum vitamin D levels and other biological parameters in a consecutive series of 61 long-term (≥3 years) unilateral TC survivors with a median a follow-up of 4 years and in a cohort of healthy males. Deficient vitamin D levels were observed in 10 (17%) of the 58 long-term unilateral TC survivors but were not reported in healthy males (p=.019, Fisher test). Median vitamin D levels were 18.6 ug/L in 58 assessable TC survivors and 23.6 ug/L in 40 healthy males (p=.031). In univariate logistic regression analysis, TC diagnosis was associated with inadequate levels of vitamin D (p=.047). Vitamin D levels were lower when follow-up was > 10 years, albeit this difference was not statistically significant (p=.074). Long-term (especially > 10 years) TC survivors may have difficulty maintaining optimal vitamin D levels. Larger studies are needed to better characterize vitamin D status and possible correlations with premature hormonal aging reported in long-term TC survivors.

PD24-10 SINGLE CENTER OUTCOMES OF TESTICULAR SPERM ASPIRATION (TESA)

You have accessJournal of UrologyInfertility: Therapy1 Apr 2014PD24-10 SINGLE CENTER OUTCOMES OF TESTICULAR SPERM ASPIRATION (TESA) Alexander Chow, Michelle Yu, Stephen Larsen, and Laurence Levine Alexander ChowAlexander Chow More articles by this author , Michelle YuMichelle Yu More articles by this author , Stephen LarsenStephen Larsen More articles by this author , and Laurence LevineLaurence Levine More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2001AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In the last few decades, the demand for assisted reproductive techniques has greatly increased, particularly for the azoospermic man. Microscopic testicular sperm extraction (micro-TESE) has emerged as the favored approach for sperm retrieval. However, this procedure is invasive, usually requires general anesthesia, use of a microscope, has a significant economic burden, and in some, prolonged recovery. TESA was first offered in the 1990’s, with few recent outcome reports. Prior retrieval rates using TESA range from 10 – 49%. We evaluated our experience with TESA for men with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) for cryopreservation for fresh in-cycle use. METHODS The complete records of 161 men from 1999 – 2012 were reviewed for concentration of sperm per high power field, motility (%), forward progression (%) viability (%), and survival of a freeze-thaw cycle. All the sperm analysis post-extraction was completed at one fertility center. All procedures were performed under sedation and local anesthesia. Preoperative FSH and testosterone for all patients were obtained. RESULTS Of our 161 patients, 47 had OA while 115 had NOA. 1 patient had cystic fibrosis, 15 had known history of varicoceles, 7 had history of unilateral testicular cancer s/p orchiectomy, 1 had Conn’s syndrome, 4 had cryptorchidism, 10 with congenital bilateral absence of the vas deferens and 36 were post-vasectomy. Sperm was successfully obtained from at least one testicle if not bilaterally in 107 patients, a success rate of 66%. In 47 patients with OA, 46 patients had successful sperm aspiration yielding a 97.8% success rate, while in 61 out of 115 NOA patients viable sperm was aspirated with a success rate of 53.0%. In patients with NOA, 38 (33%) had elevated FSH levels with sperm successfully retrieved from only 7/38 patients (18%). While 9 OA patients had elevated FSH levels (19%) with 9/9 successful sperm retrieval. There were no postoperative adverse events, including hematoma, atrophy, new hypogonadism or hospital readmission. Return to daily activities was typically in 2 days. CONCLUSIONS TESA appears to offer a reasonably high likelihood of viable sperm retrieval in men with OA and NOA, which compares well with micro-TESE. The advantages of TESA include a quicker, less invasive, simpler, less costly alternative to micro-TESE, with a low-risk for side effects. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e734 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Alexander Chow More articles by this author Michelle Yu More articles by this author Stephen Larsen More articles by this author Laurence Levine More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Fertility outcome of patients with testicular tumor: before and after treatment

Testicular cancer (TC) is the most curable type of cancer, with a survival rate of more than 95%. Oncologists are faced with the challenge that gonadotoxic cancer treatments can compromise future fertility, either temporarily or permanently. Our aim was to investigate the long-term effects of TC treatments on male fertility and on the offspring of patients who had received these treatments. Between January 1996 and December 2010, 125 eligible patients, ranging from 18 to 54 years (median age 36.3 ± 15.7), with unilateral TC underwent surgery, chemotherapy or radiotherapy at our center. Some of these patients had their semen samples cryopreserved in the Shanghai Human Sperm Bank. The clinical data were evaluated, and questionnaire and telephone follow-up surveys were given to all patients. The data were analyzed to determine the patients’ fertility status pre- and posttreatment. Of the 125 eligible patients, 93.6% (117/125) were accessible and were evaluated. Among 81 men who were married before diagnosis, 21 had conceived successfully before diagnosis and six reported azoospermia. Posttreatment conception was attempted by 73 men; of these, 16 conceived naturally and 19 conceived by artificial reproductive techniques, resulting in 37 healthy babies with no congenital malformations. Of the patients who had not conceived before treatment, 21.9% (21/96) banked their sperm and 23.8% of these patients (5/21) subsequently used the banked sperm. Retroperitoneal lymph node dissection, chemotherapy and radiotherapy were the most highly correlated with lack of conception post-TC treatment. Sperm banking should be recommended to TC patients with the desire for biological conception. There is no evidence to suggest that TC treatments are associated with birth defects or childhood malignancies.

Bilateral Germ-Cell Testicular Cancer – Long- Term Experience

Germ cell testicular cancer (TC) patients have an increased risk of developing a contralateral TC. This paper presents a retrospective analysis of patients with bilateral TC from a database of a single center and aims to highlight the need for an individual approach. In the study period from January 1970 to June 2013, a total of 1,438 patients with primary TC were diagnosed. The group comprised of 1,370 patients with unilateral TC and 68 patients with bilateral TC. Bilateral TC patients were evaluated regarding the age at presentation and the histology of tumor and then compared with the group of patients with unilate-ral TC. The mean age of the patients with unilateral TC was 31.7 years. This group of patients consisted of 408 patients with seminoma and 962 patients with non-seminomatous TC. The group of 68 patients with bilateral TC involved 63 patients with metachronous disease and five patients who developed TCs simultaneously. The mean age at diagnosis of primary tumor in patients with metachronous bilateral TC (25.8 years) was significantly earlier in comparison to patients with unilateral disease. Among 24 patients with seminoma there were 17 patients who subsequently developed a second malignancy of an identical histological type. In the group of 39 patients with initial non-seminomatous TC there were 15 patients with discordant histology of the second tumor. In the metachronous disease group, patients with primary seminoma were significantly older than those with initial non-seminomas. All patients with unilateral TC have an increased risk of developing a contralateral TC, years and even decades after the initial diagnosis. Management of subsequent TC should be individualized for each patient according to the histology and clinical stage of the primary tumor, as well as the therapeutic strategy applied initially. The further management should involve a long-term follow-up and life-long testosterone substitution.

Testis sparing surgery in a case of small unilateral testicular cancer

A 22-year-old male presented at our institution with an incidentally ultrasound-detected testicular tumor. Magnetic resonance imaging showed a contrast-enhanced right intratesticular mass over 1 cm in size. The patient underwent testis sparing surgery. Pathologic examination revealed seminoma. A follow-up nine months later showed no residual tumor, a normal contour of the testis and no evidence of atrophy. Testis sparing surgery is an option for patients with small unilateral testicular tumors even in the presence of a healthy contralateral testis.

Altered bone status in unilateral testicular cancer survivors: Role of CYP2R1 and its luteinizing hormone-dependency.

Recent data suggest a potential role of testis in vitamin D activation, where Leydig cells could represent key players in this process since they express the highest amount of CYP2R1, a key enzyme involved in vitamin D 25 hydroxylation. To evaluate bone status in unilateral orchiectomy and to assess in vivo and in vitro LH-dependency of Vitamin D 25 hydroxylation. 125 normotestosteronemic patients with testicular cancer (TC), featured by unilateral orchiectomy and 41 age-matched healthy male controls were studied in the Center for Human Reproduction Pathology at the University of Padova. To evaluate LH-dependency of Vitamin D 25 hydroxylation in vitro, Leydig cell cultures were stimulated with hCG and assessed for CYP2R1 expression, whereas in vivo 10 hypogonadotropic hypogonadal (HH) patients were evaluated before and after treatment with gonadotropins for bone metabolism markers. Hormonal pattern and bone metabolism markers were measured in all subjects, whereas 105 patients and 41 controls underwent bone densitometry by DEXA. In TC patients 25-hydroxyvitamin D levels were significantly lower compared to controls. Furthermore, 23.8% of patients with TC displayed low bone density (Z-score <-2 SD). None of the 41 control subjects showed any significant alteration of BMD. In vitro and in vivo studies revealed that CYP2R1 expression in Leydig cells appeared to be hCG dependent. Our data show an association between TC and alteration of the bone status, despite unvaried androgen and estrogen levels, suggesting the evaluation of bone status and possible vitamin D deficiency in TC survivors.

Reproduction rates prior to diagnosis of testicular cancer: Does the testicular dysgenesis syndrome exist?

4563 Background: Incidence of testicular cancer (TC) in Norway is approximately three times as high as 50 years ago and the highest world-wide. A “testicular dysgenesis syndrome” (TDS) comprising reduced fertility, cryptorchidism, hypospadias, and ultimately testicular cancer (TC) has been hypothesized. Therefore, rising TC incidence has been considered a “whistle blower” for declining male fertility. According TDS, pre-diagnosis fertility in males developing TC is lower than in the general male population. Methods: Each former TC patient diagnosed in Norway 1967-2007 (n=3.574) was age-matched with five controls from the general population (n=17.865). Complete fatherhood information was retrieved from the Medical Birth Registry. Unadjusted proportions of TC men with 1 child, > 1 child (stratified by seminoma/nonseminoma and unilateral/bilateral TC) were compared to those of the controls by Chi-square tests. Pre-diagnosis fertility rates ratios were calculated with conditional logistic regression, stratified by histology and uni-vs bilaterality thus adjusting for age and diagnostic period. Results: A slightly higher proportion of TC patients (44.4%, n=1,587) as compared to their controls (42.6%, n=7,602) fathered ≥ 1child prior to diagnosis, p=0.041.Overall, the proportions of TC pts having one, two or ≥ 3 children before their diagnosis were always higher compared to their controls, p=0.11. When stratified by histology the rates were OR=1.04, 95%CI [0.97-1.12], p=0.285 and OR=1.05, 95%CI [0.97-1.14], p=0.237 for seminoma and non-seminoma, respectively. For bilateral and unilateral TC the rates were OR=1.05, 95%CI [0.99-1.11], p=0.109 and OR=0.99, 95% CI [0.74-1.31],p=0.923, respectively. Conclusions: Fatherhood was slightly more frequent among men developing TC than in controls. Pre-diagnosis fertility rates of males who developed TC were similar to those of age-matched males from the general population. Interestingly, also males developing TC in both testicles did not have inferior fatherhood rates before diagnosis. These results challenge the appropriateness of the testicular dysgenesis syndrome.

Cardiovascular Risk Factors and Morbidity in Long-Term Survivors of Testicular Cancer: A 20-Year Follow-Up Study

To evaluate the prevalence of cardiovascular risk factors and long-term incidence of cardiovascular disease (CVD) in survivors of testicular cancer (TC). Overall, 990 men treated for unilateral TC (1980 to 1994) were included in this national follow-up study (2007 to 2008). They were categorized into four treatment groups: surgery (n = 206), radiotherapy only (RT; n = 386), chemotherapy only (n = 364), and combined RT/chemotherapy (n = 34). Age-matched male controls from the general population (ie, NORMs) were included (n = 990). Survivors of TC who were diagnosed with CVD before or within 2 years after the TC diagnosis were excluded from analyses of CVD end points. Median observation time was 19 years (range, 13 to 28 years). All cytotoxic treatment groups had significantly increased prevalences of antihypertensive medication, and survivors in the RT and RT/chemotherapy groups had higher prevalences of diabetes (RT: odds ratio [OR], 2.3; 95% CI, 1.5 to 3.7; RT/chemotherapy: OR, 3.9; 95% CI, 1.4 to 10.9) compared with NORMs. Overall 74 survivors of TC (8.0%) experienced atherosclerotic disease during follow-up. Increased risks for atherosclerotic disease were observed in age-adjusted Cox regression analyses after any cytotoxic treatment when compared with surgery only (RT: hazard ratio [HR], 2.3; 95% CI, 1.04 to 5.3; chemotherapy: HR, 2.6; 95% CI, 1.1 to 5.9; RT/chemotherapy: HR, 4.8; 95% CI, 1.6 to 14.4). Treatment with cisplatin, bleomycin, and etoposide (BEP) alone had a 5.7-fold higher risk (95% CI, 1.9 to 17.1 fold) for coronary artery disease compared with surgery only and a 3.1-fold higher risk (95% CI, 1.2 to 7.7 fold) for myocardial infarction compared with NORMs. Treatment with infradiaphragmatic RT and/or cisplatin-based chemotherapy, particularly the BEP regimen, increases the long-term risk for CVD in survivors of TC.

Cardiovascular risk in long-term testicular cancer survivors.

4533 Background: The aim was to evaluate the incidence of non-fatal cardiovascular disease (CVD) and risk profile in testicular cancer (TC) survivors (TCS). Methods: 990 men treated for unilateral TC (1980-1994) were included in this national follow-up study (2007-2008) including physical examination, blood samples and a questionnaire. Patients were categorized into four treatment groups: Surgery (n=206), radiotherapy only (RT, n=386), cisplatin-based chemotherapy only (chemo, n=364) and combined RT/chemotherapy (RT/chemo, n=34). Age-matched male controls from the general population (NORMs) were recruited from the Tromsø Study (n=990). Men diagnosed with CVD before or within two years after the TC diagnosis were excluded from analyses of CVD endpoints (age-adjusted Cox regression). CVD endpoints were 1) coronary heart disease (CHD) and 2) total CVD. All CVD diagnoses were validated by medical records (TCS). For comparisons to NORMs, the combination of stroke/myocardial infarction (MI) was the endpoint as only these diagnoses were validated. Results: Median observation time was 19 years (range 13-28). Overall 92 TCS (9.9%) experienced CVD events during follow-up. Compared with surgery group, the chemo (HR 2.6, 95% CI 1.0-6.9) and the RT/chemo group (HR 5.3, 95% CI 1.5-18.5) had increased risks for CHD. Increased risks for total CVD were observed after any cytotoxic treatment (RT: HR 2.3, 95% CI 1.1-4.7; chemo: HR 2.4, 95% CI 1.1-5.0; RT/chemo: HR 5.2, 95% CI 2.0-13.5). Compared with NORMs, TCS had 1.7 times higher risk (95% CI 1.0-2.8) for stroke/MI, with the highest risks for the RT (HR 2.0, 95% CI 1.2-3.5) and the RT/chemo group (HR 4.5, 95% CI 1.6-12.8). All treatment groups except surgery group had increased prevalence of antihypertensive medication compared to NORMS (22% vs. 13%), highest for the chemo (OR 3.3, 95% CI 2.4-4.5) and the RT/chemo group (OR 4.1, 95% CI 1.9-8.8). Survivors in the RT and RT/chemo group had higher levels of micro CRP (RT: β=0.38 mg/l, p<.001, RT/chemo: β=0.63 mg/l, p=0.014), and a higher prevalence of diabetes (RT: OR 2.3, 95% CI 1.5-3.6; RT/chemo: OR 3.9, 95% CI 1.4-10.9). Conclusions: Treatment with infradiaphragmatic RT and/or cisplatin-based chemotherapy, particularly when combined, increases the long-term risk for CVD. No significant financial relationships to disclose.

Paternity and Testicular Function Among Testicular Cancer Survivors Treated With Two to Four Cycles of Cisplatin-Based Chemotherapy

BackgroundPreserved fertility is an important issue for testicular cancer (TC) survivors. ObjectiveOur aim was to examine any difference regarding paternity and testicular function following two, three, or four cycles of cisplatin-based chemotherapy for TC. Design, setting, and participantsA national multicentre follow-up survey assessing morbidity among survivors of unilateral TC diagnosed from 1980 to 1994 was conducted during the period 1998 to 2002. Of the 1814 men invited, 1462 (80.6%) participated by responding to a mailed questionnaire and/or undergoing a clinical examination including laboratory assessments. The present study includes the 316 participants up to 65 yr of age treated with two to four cycles of standard cisplatin-based chemotherapy without additional treatment beyond surgery. MeasurementsSelf-reported paternity following treatment for TC according to number of cycles was assessed among men who reported antegrade ejaculation and attempts at posttreatment conception (n=106). Kaplan-Meier analysis, log-rank test, and Cox regression were applied. Gonadal hormones (n=305–314) and sperm counts (n=71) by number of cycles were assessed by linear by linear association or Mann-Whitney tests. Results and limitationsAt median 12-yr follow-up, 80% (85 of 106) had succeeded in their attempts of achieving posttreatment paternity (two cycles: 100%; three: 83%; four: 76%; p=0.022). For all patients the 15-yr actuarial paternity rate was 85%. The association between posttreatment paternity and number of cycles remained significant in the multivariate analysis (p=0.032). High serum follicle-stimulating hormone values were more common with increasing number of cycles (p=0.037), but there were no differences in serum luteinising hormone, serum testosterone, or sperm counts. Few men treated with two cycles and a limited number of sperm samples are the main limitations of this study. ConclusionsThe prospects of future paternity after two to four cycles of cisplatin-based chemotherapy are good, and our data suggest that the prospects improve with decreasing number of cycles.

Intratubular germ cell neoplasms of the testis and bilateral testicular tumors: Clinical significance and management options

Objectives:Intratubular germ cell neoplasia (ITGCN) is the precursor lesion for invasive testicular germ cell tumors (TGCTs) of adolescents and young adults. The rising incidence of these tumors has prompted a rigorous investigation of the etiology, diagnosis and management of ITGCN. Bilateral testicular cancer is closely linked with ITGCN, as patients with unilateral testicular cancer are at the highest risk for a future malignancy in the contralateral testicle.Methods:A literature review directed at ITGCN and bilateral testis cancer was performed using the Medline/PubMed database. Our review focused on the pathogenesis, risk factors, diagnosis and treatment regimens utilized.Results:Major advances have been made in the understanding of ITGCN over the past 30 years. There is evidence that TGCTs arise from ITGCN, ITGCN is closely related to fetal gonocytes, and that events in pre- and perinatal period may result in abnormal persistence of fetal gonocytes leading to ITGCN and subsequent TGCT. Controversy exists regarding the need to biopsy men at increased risk of TGCT, as well as the best approach to managing patients with known ITGCN. Bilateral testicular cancer has excellent outcomes in the current era of platinum-based chemotherapy.Conclusion:The optimal management of patients at risk for ITGCN and future TGCT is still a matter of debate. Individualization of management, including biopsy and treatment, should be based on risk factors for TGCT, compliance with potential surveillance, and patient preferences particularly with regard to fertility.

Observational Study of Prevalence of Long-term Raynaud-Like Phenomena and Neurological Side Effects in Testicular Cancer Survivors

BackgroundSensory neuropathy (paresthesias), tinnitus, hearing impairment, and Raynaud phenomena are side effects of cisplatin-based chemotherapy used to treat testicular cancer patients. We assessed the long-term occurrence of these side effects among testicular cancer survivors according to the treatment they received.MethodsA total of 1814 men who were treated for unilateral testicular cancer in Norway during 1980–1994 were invited to participate in a national multicenter follow-up survey conducted during 1998–2002. The men were allocated to six groups according to the treatment they had received. Self-reported symptoms were assessed by a mailed questionnaire that included the Scale for Chemotherapy-Induced Neurotoxicity. A total of 1409 participants who responded to the questionnaire and/or underwent audiometry were assessable in this study. Respondents to the questionnaire (n = 1402) scored the relevant symptoms according to how troubled they were by each (not at all, a little, quite a bit, or very much). Hearing impairment was objectively assessed by audiometry at 4000 Hz in 755 men (seven of whom did not respond to the questionnaire). Group comparisons of symptom assessments were performed with χ2 or Kruskal–Wallis tests. Associations between relevant factors and self-reported symptoms or hearing impairment measured by audiometry were assessed using proportional odds ordinal logistic regression models and linear regression models, respectively. All statistical tests were two-sided.ResultsThe median follow-up for the 1409 assessable men was 10.7 years (range = 4–21 years). All chemotherapy groups had statistically significantly higher odds for increasing severity of all assessed symptoms and inferior audiometric results compared with men who did not receive chemotherapy. Among chemotherapy-treated men, 39% (95% confidence interval [CI] = 35% to 43%) reported Raynaud-like phenomena (defined as white or cold hands or fingers [or feet or toes] on cold exposure), 29% (95% CI = 25% to 33%) reported paresthesias in the hands or feet, 21% (95% CI = 18% to 25%) reported hearing impairment, and 22% (95% CI = 19% to 26%) reported tinnitus as major symptoms troubling them quite a bit or very much. Hearing impairment (odds ratio [OR] = 5.3, 95% CI = 3.0 to 9.2) and tinnitus (OR = 7.1, 95% CI = 4.1 to 12.4) were particularly common in the dose-intensive chemotherapy group compared with the no chemotherapy group. Men who were treated with radiotherapy had higher odds of self-reported paresthesias in feet compared with those not treated with radiotherapy (OR = 1.5, 95% CI = 1.01 to 2.1, P = .04).ConclusionLong-term survivors of testicular cancer who were treated with cisplatin-based chemotherapy were more often troubled by dose-dependent neurological side effects and Raynaud-like phenomena compared with those who were not treated with chemotherapy.

Management of the contralateral testicle in patients with unilateral testicular cancer

Patients with a prior history of a germ cell tumor of the testicle are known to have an increased risk of development of a second germ cell tumor in the contralateral testicle. It is believed that all patients who develop a germ cell tumor of the testicle have a precursor lesion know as carcinoma in situ (CIS) or intratubular germ cell neoplasia. Approximately 50% of these patients will subsequently go on to develop a germ cell tumor in the testicle. A biopsy of the contralateral testicle in a patient with a previous history of a germ cell tumor of the testicle has been advocated by some, while others recommend a biopsy only in patients with other risk factors as well. The arguments for biopsy are that intervention may be used to prevent the development of a second germ cell tumor when CIS is detected. In this review we present the arguments for and against a biopsy of the contralateral testicle, review the techniques of biopsy as well as its complications, and discuss the interventions employed to prevent CIS from progressing.

Damage of hormonal function and bone metabolism in long-term survivors of testicular cancer

Improved survival of testicular cancer (TC) patients leads to rising of interest on the disease consequences for the whole organism (impact on hormonal status, bone metabolism). The aim of the study was to present three years experience with hormonal and osteologic examination in long-term survivors of TC. During the period of 11/2005-1/2009 879 patients who were previously treated for TC (823 with unilateral, 56 with bilateral disease) were examined. Each patient underwent hormonal and osteologic examination, results of which were associated with therapy following orchiectomy and with the time interval since the primary therapy. The median follow-up time in patients with unilateral TC was 96 months since the therapy. Mean age at the time of examination was 32 years. Testosterone deficiency was observed in 171 patients (19.5%), increased LH in 168 patients (19.1%), increased S-CTx in 388 patients (44.1%). Bone damage (osteopenia and/or osteoporosis) was observed in 445 patients (50.6%). The median follow-up time in patients with bilateral TC was 175 months. Mean age at the time of examination was 27 years. Testosterone deficiency was observed in 47 patients (83.9%), increased LH in 45 patients (80.4%), increased S-CTx in 31 patients (55.4%). Bone damage was observed in 41 patients (73.2%). Hormonal examination and testosterone substitution may be recommended as an important aspect of patient s follow-up in bilateral TC, moreover in unilateral disease. The important part of standard examination algorithm should be also osteological examination to prevent osteopenia or even osteoporosis development.

Is Contralateral Testicular Biopsy Warranted at the Time of Orchidectomy?

Objective: Previous studies have suggested that biopsy of the contralateral testis at the time of radical inguinal orchidectomy for unilateral testicular cancer should be performed to exclude intra tubular germ cell neoplasia (ITGCN). This practice has become routine in many urology departments. We reviewed the histological outcome of contralateral testis biopsy in patients with testis cancer to determine if it was appropriate to routinely continue this practice. Methods: The medical records of all men presenting to our institution with testicular cancer between 1998 and 2006 were retrospectively reviewed. The histological diagnosis following inguinal orchidectomy and the outcome of contralateral testis biopsy (where this had been performed) were recorded. The median duration of follow-up was 56 months and the incidence of metachronous tumours during this period was noted. Results: There were 193 consecutive cases of testicular cancer (seminoma, n = 108; nonseminatous germ cell tumour [NSGCT], n =73; non-GCT, n =8; lymphoma, n = 4). Nine patients had a history of maldescent, 12 had microlithiasis and 9 had atrophic testes. One hundred and fifty-one men had contralateral testis biopsies, but there were no cases of ITGCN, regardless of original tumour type or stage. Four patients (all with initial seminomas) developed metachronous tumours, 3 were seminomas and 1 was a mixed GCT. In 3 of the 4 cases, the previous contralateral testis biopsy was normal while the fourth patient was not biopsied at the time of his initial surgery. There were 4 (3%) cases of haematoma following contralateral testis biopsy. Conclusion: Contralateral testis biopsy was unhelpful in predicting metachronous tumour occurrence, carries a small risk of morbidity and should not be routinely performed in men undergoing orchidectomy for testicular cancer.