Long-term Survivors Of Testicular Cancer Research Articles

Components of the metabolic syndrome in long-term survivors of testicular cancer

Components of the metabolic syndrome in long-term survivors of testicular cancer

Components of the metabolic syndrome in long-term survivors of testicular cancer

Components of the metabolic syndrome in long-term survivors of testicular cancer

Long-term complications of platinum-based chemotherapy in testicular cancer survivors

The purpose of this study was to describe the rates of cardiovascular and other medical complications related to the use of platinum-based chemotherapy in American testicular cancer survivors. The study sample consisted of 143 eligible long-term testicular cancer survivors. Participants were interviewed, their medical records were reviewed, and blood was obtained for cholesterol measurement during their follow-up visit. The mean follow-up time was 8.4 yr, and their mean age at follow-up was 41.2 yr; 72.7% had had non-seminoma, and 82.5% had received platinum-based chemotherapy. Hypertension rates in the platinum-treated group increased significantly from baseline to follow-up; however, once adjusted for blood pressure measurement (undiagnosed hypertension), no such increase was seen, and hypertension rates were already higher than national estimates at baseline in all groups. At the follow-up visit, the rates of hyperlipidemia (adjusted for measured cholesterol level) in both platinum- and non-platinum-treated groups (28.4% and 37.5%, respectively) were higher than national estimates (16.9%). Rates of coronary artery disease were higher in those who had received platinum and radiation (11.1%) than in those who had received platinum alone (4.3%), but this difference was not statistically significant. As suggested by previous studies, platinum-based chemotherapy may be associated with hypertension, hyperlipidemia, and coronary artery disease. However, our data suggest that undiagnosed hypertension and hyperlipidemia may be significant confounders, and we also observed a trend toward lower testosterone levels in participants who experienced cardiovascular complications.

Treatment-related differences in cardiovascular risk factors in long-term survivors of testicular cancer

Treatment in testicular cancer survivors (TCSs) may be followed by cardiovascular disorders. We have examined whether today's three treatment modalities are associated with a biochemical cardiovascular risk profile. In this cross sectional study serum inflammatory markers, atherogenic lipoproteins and gonadal hormones were measured in 589 orchiectomized TCSs who have been treated 5-20 years previously. There were 140 patients treated by surgery alone (SURG), 231 who had had infradiaphragmatic radiotherapy alone (RAD), and 218 who had chemotherapy with or without additional surgery (CHEM). (1) The RAD group had higher levels of high-sensitivity C-reactive protein and soluble CD40 ligand compared to the SURG group. (2) The CHEM group had lower levels of high density lipoprotein cholesterol and an increased apolipoprotein B/apolipoprotein A-1 ratio than the SURG group. The prevalence of metabolic syndrome was higher in the CHEM group than in the SURG group. (3) Hypogonadism was significantly more prevalent in the CHEM than in the SURG group. Treatment for TC was related to long-term biochemical cardiovascular risk factors by different pathways: Radiation treatment is followed by elevated serum markers of chronic inflammation and endothelial dysfunction, whereas chemotherapy is followed by the development of atherogenic lipid changes and of the metabolic syndrome. This study provides justification for a prospective study of the impact of these treatment modalities on cardiovascular risk in testicular cancer survivors. In the interim testicular cancer survivors should monitor cardiovascular risk over time.

Is the Sexual Function Compromised in Long-Term Testicular Cancer Survivors?

ObjectivesThis study explores sexual function in a large unselected sample of Norwegian testicular cancer survivors (TCSs) by comparing the results with population data. MethodsThe study included 1084 TCSs aged 20–59 yr with mean follow-up time of 11.1 (range: 5–21) yr. They provided information about their medical, social, lifestyle, and familial situations on a questionnaire that included the Brief Male Sexual Function Inventory (BSFI). Outcome measures were mean BSFI domain scores and BSFI-based prevalence rates of sexual problems. The BSFI findings of an age-adjusted random sample of the Norwegian male population (N=929) constituted normative data (NORM). Descriptive statistics and logistic regression analyses were applied, and a significance level of <0.01 was applied. ResultsCompared with NORM, TCSs had significantly worse scores on ejaculatory and sexual problems in both young (20–39 yr) and middle-aged (40–59 yr) groups. In the young group, sexual satisfaction was significantly better in TCSs versus NORM. Overall sexual problems were expressed by 38.8% of the TCSs versus 35.5% in NORM. In multivariate analyses, overall sexual problems in TCSs were significantly associated with increasing age, lack of a partner, and a higher anxiety score, while ejaculation problems showed significant association with lack of a partner, and a trend for chemotherapy and neurotoxic side effects (p=0.02). ConclusionsCompared with NORM, ejaculatory function was compromised in TCSs. Overall sexual problems in TCSs were associated with factors also observed in NORM. Better sexual satisfaction in young TCSs compared with NORM should be noted.

Components of the metabolic syndrome in long-term survivors of testicular cancer

A possible explanation of the excess cardiovascular risk in testicular cancer (TC) survivors is development of metabolic syndrome. The association between metabolic syndrome and TC treatment is examined in long-term survivors. In a national follow-up study (1998-2002), 1463 TC survivors (diagnosed 1980-1994) participated. Patients >60 years were excluded in the present study, leaving 1135 patients eligible. The patients were divided in four treatment groups: surgery (n = 225); radiotherapy (n = 446) and two chemotherapy groups: cumulative cisplatin dose (Cis) <or=850 mg (n = 376) and Cis >850 mg (n = 88). A control group consisted of 1150 men from the Tromsø Population Study. Metabolic syndrome was defined according to a modified National Cholesterol Education Program definition. Both chemotherapy groups had increased odds for metabolic syndrome compared with the surgery group, highest for the Cis >850 group [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.6-4.7]. Also, the Cis >850 group had increased odds (OR 2.1, 95% CI 1.3-3.4) for metabolic syndrome compared with the control group. The association between metabolic syndrome and the Cis >850 group was strengthened after adjusting for testosterone, smoking, physical activity, education and family status. TC survivors treated with cisplatin-based chemotherapy have an increased risk of developing metabolic syndrome compared with patients treated with other modalities or with controls.

Recurrence Pattern and Proposed Surveillance Protocol Following Post-Chemotherapy Retroperitoneal Lymph Node Dissection

We evaluated the recurrence pattern in patients with nonseminomatous germ cell tumors treated with post-chemotherapy retroperitoneal lymph node dissection and determined the optimal surveillance strategy in these patients. Between 1980 and 2003, 236 patients with clinical stage IIA-III nonseminomatous germ cell tumors underwent post-chemotherapy retroperitoneal lymph node dissection. Patients with increased preoperative tumor markers (alpha-fetoprotein greater than 15 ng/ml and/or beta-human chorionic gonadotropin greater than 2.2 U/ml) were excluded from study resulting in 198 patients for analysis. We retrospectively reviewed medical records for pertinent clinical and treatment related outcomes. In our patient population recurrence developed in 45 (23%) patients and 22 (11%) died of disease at a median followup of 41 months (range 6 to 250) after retroperitoneal lymph node dissection. The clinical stage of testis cancer was IIA in 17, IIB in 49, IIC in 83 and III in 49 patients. Of the 45 patients with postoperative recurrence, 16 had concomitant multiple sites of recurrence with a total of 64 sites reported. Of the cases of recurrence 21 (46.7%) were in those of clinical stage III, 18 (40%) stage IIC and 6 (11.8%) stage IIB disease. The most frequent site of recurrence was the chest (32, 49%), followed by the abdomen (14, 22%), supraclavicular lymph nodes (8, 13%), brain (5, 8%) and other sites (5, 8%). Based on the recurrence pattern we propose stage specific surveillance guidelines for the followup of patients after post-chemotherapy retroperitoneal lymph node dissection. These guidelines help identify patients at high risk for disease progression and, thus, requiring more stringent postoperative followup.

Self-reported paresthesias, Raynaud’s phenomena, tinnitus, and hearing impairment in a large cohort of long-term testicular cancer (TC) survivors

4547 Background: Persisting side-effects of treatment may impair the well-being of TC survivors. The aim of this study was to assess long-term Raynaud’s phenomena, oto-, and neurotoxicity related to prior therapy. Methods: A follow-up survey was conducted in men treated for TC 1980–1994 in Norway. The 1319 eligible responders had a median follow-up time of 11 years (range 4–21) and were allocated to four separate treatment groups: Surgery (Surg), Radiotherapy (Rt), and chemotherapy (Cisplatin [Cis] ≤ 850 mg and Cis &gt; 850 mg). The questionnaire included six items assessing the relevant toxicities. The responders’ scores were dichotomized [minor (“not at all” or “a little”) vs. major (“quite a bit” or “very much”)] and analyzed by logistic regression with Surg as reference. Results: The proportion of cases (%) reporting major symptoms and the corresponding Odds ratios (OR) varied significantly between treatment groups ( table ). Rt was not statistically significantly different from Surg for any symptom, but showed a trend for higher scores of paresthesias in the feet. Cis &gt; 850 mg differed significantly for all symptoms with major symptoms reported by 25–49% with the highest OR (8.1) for Raynaud’s phenomena in hands. Apart from Raynaud’s phenomena, paresthesias in feet were the only symptom significantly different in Cis &lt; 850 mg compared to Surg. Conclusions: Toxicities induced by cisplatin-based chemotherapy persist in many TC survivors. A cold climate may contribute to the high perception of Raynaud’s phenomena in Norwegian TC survivors. [Table: see text] No significant financial relationships to disclose.

The Metabolic Syndrome and Disturbances in Hormone Levels in Long-Term Survivors of Disseminated Testicular Cancer

Purpose The metabolic syndrome may be an important risk factor for cardiovascular disease in long-term survivors of testicular cancer (TC). We investigated the associations between hormone levels and the metabolic syndrome in these men. Patients and Methods We included TC patients cured by orchidectomy and cisplatin-based chemotherapy, stage I TC patients after orchidectomy only, and healthy men of comparable age. Presence of the metabolic syndrome was determined using guidelines from the National Cholesterol Education Program Adult Treatment Panel III. Thyroid-stimulating hormone, follicle-stimulating hormone (FSH), inhibin B, luteinizing hormone (LH), total testosterone, sex-hormone–binding globulin, free testosterone, estradiol, dehydroepiandrosterone sulfate, and insulin-like growth factor 1 were determined in blood. Cortisol metabolite excretion was measured in urine. Results Eighty-six chemotherapy patients (median follow-up, 7 years) were compared with 44 stage I patients and 47 controls. LH and FS...

Blood pressure and body mass index in long-term survivors of testicular cancer: Sagstuen H, Aass N, Fossa SD, Dahl O, Klepp O, Wist EA, Wilsgaard T, Bremnes RM, Department of Oncology, Institute of Clinical Medicine, University of Tromso, Tromso, Norway

To evaluate blood pressure and body mass index (BMI) in long-term survivors of testicular cancer (TC) treated with different modalities. One thousand eight hundred fourteen patients treated for unilateral TC in Norway (1980 to 1994) were invited to participate in a follow-up study (1998 to 2002), including measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. Of these patients, 1,289 patients (71%) participated in the study. The patients were categorized into four treatment groups: surgery (n = 242), radiotherapy (n = 547), and two chemotherapy groups, cumulative cisplatin dose ≤850 mg (n = 402) and cumulative cisplatin dose more than 850 mg (n = 98). A control group consisted of healthy males from the Tromso Population Study (n = 2,847). At diagnosis, age-adjusted regression analyses showed no differences between the treatment groups for any variables. After a median follow-up time of 11.2 years, age-adjusted SBP and DBP were significantly higher for both chemotherapy groups compared with the surgery group. Chemotherapy-treated patients had increased odds for hypertension at follow-up compared with the surgery group, and the odds were highest for the cisplatin more than 850 mg group (odds ratio = 2.4; 95% CI, 1.4 to 4.0). The cisplatin more than 850 mg group had a significantly higher 10-year BMI increase and a higher prevalence of obesity at follow-up than the surgery group. Compared with healthy controls, chemotherapy-treated patients had, at follow-up, increased SBP, increased DBP, excessive BMI increase, and a higher prevalence of hypertension. Five to 20 years after therapy, cured TC patients treated with cisplatin-based chemotherapy had significantly higher levels of blood pressure, a higher prevalence of hypertension, and an excessive weight gain compared with patients treated with other modalities and compared with healthy controls

Infarctus du myocarde précoce après chimiothérapie pour tumeur testiculaire

Introduction In long-term survivors of testicular cancer, a greater risk of developing cardiovascular disease is reported. On the other hand, acute vascular event during chemotherapy is uncommon. Case report We report on a case of acute myocardial infarction in a young man receiving chemotherapy (BEP) for testicular cancer. Discussion We suggest a causal association between chemotherapy and early myocardial infarction. The physiopathological mechanisms are discussed here.

Mechanisms of Late Cardiovascular Toxicity From Cancer Chemotherapy

Germ cell tumors (GCTs), which most commonly arise in the testes, represent one of the most curable of the solid neoplasms. This status is the consequence of treatment advances developed during the last 30 years, including surgery, radiotherapy, and chemotherapy. The 5-year survival exceeds 90%, so additional improvement in the treatment of these cancer patients must include a focus on quality of life, and on minimizing or eliminating the long-term complications of the disease and its therapy. The work by Nuver et al presented in this issue of the Journal of Clinical Oncology is novel and potentially important in this regard. Combination chemotherapy with etoposide, cisplatin, and bleomycin is the key contributor to the high cure rate in patients with GCTs. However, since the initial reported series in 1981 of Raynaud’s phenomenon as a complication of GCT treatment, evidence has been accumulating that suggests that acute and long-term vascular toxicity is the most important late consequence of cisplatin-based chemotherapy in the treatment of men with metastatic GCTs. More recent reports highlight this problem. Meinardi et al reported that five (6%) of 87 men between the ages of 30 and 42 who were in remission for longer than 10 years after cisplatin-based chemotherapy developed myocardial ischemia (observed-to-expected ratio 7.1; 95% CI, 1.9 to 18.3). Huddart et al studied all male GCT patients registered in the United Kingdom between 1982 and 1992. After a median follow-up of 10.2 years, and adjusting for age, increased risk for cardiac events was seen after chemotherapy alone (relative risk [RR] 2.59), radiation therapy (RR 2.40), and combined therapy (RR 2.78). On the basis of these and other observations, Huddart et al concluded that long-term survivors of testicular cancer have a two-fold or greater risk of developing cardiovascular disease that was not due to increases in cardiac risk factors, suggesting a direct or indirect treatment-related cardiovascular toxicity. In addition to myocardial ischemia, hypertension developed during or after therapy in 15% to 54% of GCT patients who received cisplatin-based chemotherapy. In the study by Meinardi et al, hypertension was three times more frequent in treated men than in a group of 40 men treated with orchiectomy alone for stage I disease (39% v 13%). Cholesterol may also increase after treatment. Not all observational studies support cisplatin chemotherapy as etiologically related to a statistical increase in late cardiovascular morbidity and mortality. In a Norwegian study, mortality rates were established for three periods of GCT treatment, including an interval during which cisplatin-based chemotherapy was not administered. The standard mortality rates for cardiovascular diseases were increased by 1.2 times in treated patients, regardless of whether the treatment regimen included cisplatin-based chemotherapy. These authors concluded that the introduction of cisplatin-based chemotherapy into the treatment had not yet resulted in increased death rates due to cardiovascular diseases, although they stated in the discussion that, “. . .survivors have a significantly increased risk of dying from diseases of the circulatory system. . .” Therefore, studies to elucidate potential pathophysiologic mechanisms of chemotherapy-related cardiovascular toxicity occurring during treatment would add to the evidence supporting downstream cardiac morbidity and mortality. Such studies could suggest means of prevention. In this issue of the Journal of Clinical Oncology, Nuver et al take the novel approach of prospectively examining potential immediate mechanisms that might lead to later cardiovascular toxicity in a group of 65 men with nonseminomatous GCTs who were undergoing chemotherapy with bleomycin, etoposide, and cisplatin. Selection criteria, clearly defined by the authors, reduced the study group from 131 to 65 treated patients. Six different measurements of the propensity for thrombosis and arterial injury were measured before and after treatment in these 65 patients. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 36 DECEMBER 2

The lack of long-term effect of Cisplatin based combination chemotherapy on serum cholesterol for treatment of testicular cancer.

Cisplatin based combination therapy is curative in most patients with advanced testicular cancer. Previous reports have suggested that hypercholesterolemia is a common complication in this patient group. We performed a cross-sectional study to assess further the relationship of cisplatin based chemotherapy and serum cholesterol in long-term survivors of testicular cancer. Fasting lipid profiles were obtained from 106 men previously treated for testicular cancer, of whom 34 had received cisplatin based combination chemotherapy and 72 were chemotherapy naive. Mean total cholesterol in the chemotherapy and nonchemotherapy groups was 5.50 +/- 0.20 and 5.36 +/- 0.13 mmol./l., respectively (p = 0.55). Mean high density lipoprotein cholesterol in the chemotherapy and nonchemotherapy groups was 1.09 +/- 0.04 and 1.09 +/- 0.03 mmol./l., (p = 0.94), while mean low density lipoprotein cholesterol was 3.49 +/- 0.17 and 3.40 +/- 0.11 mmol./l. (p = 0.67) respectively. The mean total-to-high density lipoprotein cholesterol ratio was 5.26 +/- 0.27 in the chemotherapy group and 5.12 +/- 0.16 in the nonchemotherapy group (p = 0.67). Body mass index was not significantly different in the 2 groups. Administering cisplatin based chemotherapy was unrelated to lipid profiles in long-term survivors of testicular cancer. Chemotherapy treated and chemotherapy naive patients had mean cholesterol levels in the borderline elevated range and body mass index in the overweight range. These potentially reversible cardiovascular risk factors have considerable importance in the overall testicular cancer population.

Paternity Following Treatment for Testicular Cancer

Studies of fertility in men treated for testicular cancer have mainly addressed serum follicle-stimulating hormone levels and sperm parameters. We assessed post-treatment paternity among long-term survivors of testicular cancer. Men (n = 1814) who had been treated for unilateral testicular cancer in Norway during 1980 through 1994 were invited to participate in a national multi-center follow-up survey in 1998 through 2002. The participants were allocated to five groups according to the treatment received after orchiectomy, including treatment at relapse (surveillance, retroperitoneal lymph node dissection, radiotherapy, low-dose chemotherapy [i.e., < or = 850 mg cisplatin], and high-dose chemotherapy [i.e., > 850 mg cisplatin]). Cox proportional hazards analysis was used to assess predictive factors for post-treatment paternity. Statistical tests were two-sided. A total of 1433 men were assessable, of whom 827 were fathers at diagnosis. Post-treatment conception was attempted by 554 men, among whom the overall 15-year actuarial post-treatment paternity rate was 71% (95% confidence interval [CI] = 66% to 75%) without the use of cryopreserved semen. This rate ranged from 48% (95% CI = 30% to 69%) in the high-dose chemotherapy group to 92% (95% CI = 78% to 98%) in the surveillance group (P < .001). The median actuarial time from diagnosis to the birth of the first child after treatment was 6.6 years overall but varied according to treatment. Assisted reproductive technologies were used by 22% of the couples who attempted conception after treatment. Dry ejaculation, treatment group, pretreatment fatherhood, and marital status were statistically significant independent predictors for post-treatment fatherhood, with dry ejaculation as the most important negative factor. Although the overall paternity rate after treatment for testicular cancer was high, the ability to conceive and the time to conception reflected the intensity of treatment. These data may help inform patients about their future ability to father biological children.

Blood Pressure and Body Mass Index in Long-Term Survivors of Testicular Cancer

To evaluate blood pressure and body mass index (BMI) in long-term survivors of testicular cancer (TC) treated with different modalities. One thousand eight hundred fourteen patients treated for unilateral TC in Norway (1980 to 1994) were invited to participate in a follow-up study (1998 to 2002), including measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. Of these patients, 1,289 patients (71%) participated in the study. The patients were categorized into four treatment groups: surgery (n = 242), radiotherapy (n = 547), and two chemotherapy groups, cumulative cisplatin dose < or = 850 mg (n = 402) and cumulative cisplatin dose more than 850 mg (n = 98). A control group consisted of healthy males from the Tromsø Population Study (n = 2,847). At diagnosis, age-adjusted regression analyses showed no differences between the treatment groups for any variables. After a median follow-up time of 11.2 years, age-adjusted SBP and DBP were significantly higher for both chemotherapy groups compared with the surgery group. Chemotherapy-treated patients had increased odds for hypertension at follow-up compared with the surgery group, and the odds were highest for the cisplatin more than 850 mg group (odds ratio = 2.4; 95% CI, 1.4 to 4.0). The cisplatin more than 850 mg group had a significantly higher 10-year BMI increase and a higher prevalence of obesity at follow-up than the surgery group. Compared with healthy controls, chemotherapy-treated patients had, at follow-up, increased SBP, increased DBP, excessive BMI increase, and a higher prevalence of hypertension. Five to 20 years after therapy, cured TC patients treated with cisplatin-based chemotherapy had significantly higher levels of blood pressure, a higher prevalence of hypertension, and an excessive weight gain compared with patients treated with other modalities and compared with healthy controls.

Serum creatinine and cholesterol levels of testicular cancer patients in long‐term follow up

Most patients with advanced testicular cancer can be cured with cisplatin-based chemotherapy. Therefore, the long-term effects of the treatment are clinically important. In the present study, we evaluated the serum creatinine and cholesterol levels of long-term survivors of testicular cancer. Serum creatinine and cholesterol levels were determined in 23 testicular cancer patients who had received cisplatin-based chemotherapy more than 5 years earlier. They were compared with a control group of 16 patients who did not receive chemotherapy. In addition, follow-up data of beyond 10 years after the initial treatment was obtained from 17 patients. We also analysed the trends of both serum creatinine and cholesterol determinations over 10 or more years using a generalized linear model. There was no significant difference in the serum creatinine and cholesterol levels 5 years after the treatment between the chemotherapy and control groups. Analysis using a generalized linear model showed a significant trend toward an increase in serum creatinine in patients who had developed renal dysfunction during chemotherapy (P = 0.0024). The elevation of the serum creatinine level was mainly observed during the first 5 years. In addition, a significant trend toward an increase in serum cholesterol was revealed in both the chemotherapy and control groups. Patients who have developed renal dysfunction during chemotherapy may be at risk of gradually increasing serum creatinine levels even after it has become normal. Although further analysis is needed, we recommend long-term follow up in the survivors of metastatic testicular cancer patients treated with cisplatin-based chemotherapy.

Fertility, gonadal and sexual function in survivors of testicular cancer

Modern treatments cure most testicular cancer patients, so an important goal is to minimise toxicity. Fertility and sexual functioning are key issues for patients. We have evaluated these outcomes in a cross-sectional study of long-term survivors of testicular cancer. In total, 680 patients treated between 1982 and 1992 completed the EORTC Qly-C-30(qc30) questionnaire, the associated testicular cancer specific module and a general health and fertility questionnaire. Patients have been subdivided according to treatment received: orchidectomy either alone (surveillance, S n=169), with chemotherapy (C, n=272), radiotherapy (R, n=158), or both chemotherapy and radiotherapy (C/RT n=81). In the surveillance group, 6% of patients had an elevated LH, 41% an elevated FSH and 11% a low (<10 nmol l−1) testosterone. Hormonal function deteriorated with additional treatment, but the effect in general was small. Low testosterone was more common in the C/RT group (37% P=0.006), FSH abnormalities were more common after chemotherapy (C 49%, C/RT 71% both P<0.005) and LH abnormalities after radiotherapy (11% P<0.01) and chemotherapy (10%, P<0.001). Baseline hormone data were available for 367 patients. After treatment, compared to baseline, patients receiving chemotherapy had significantly greater elevations of FSH (median rise of 6 (IQR 3–9.25) iu l−1 compared to 3 (IQR 1–5) iu l−1 for S; P<0.001) and a fall (compared to a rise in the surveillance group) in median testosterone levels (−2 (IQR −8.0 to −1.5) vs 1.0. (IQR −4.0–4.0) P<0.001). Patients with low testosterone (but not elevated FSH) had lower quality of life scores related to sexual functioning on the testicular cancer specific module and lower physical, social and role functioning on the EORTC Qly C-30. Patients with a low testosterone also had higher body mass index and blood pressure. Treatment was associated with reduction in sexual activity and patients receiving chemotherapy had more concerns about fathering children. In total, 207 (30%) patients reported attempting conception of whom 159 (77%) were successful and a further 10 patients were successful after infertility treatment with an overall success rate of 82%. There was a lower overall success rate after chemotherapy (C 71%; CRT 67% compared to S 85% (P=0.028)). Elevated FSH levels were associated with reduced fertility (normal FSH 91% vs elevated 68% P<0.001). In summary, gonadal dysfunction is common in patients with a history of testicular cancer even when managed by orchidectomy alone. Treatment with chemotherapy in particular can result in additional impairment. Gonadal dysfunction reduces quality of life and has an adverse effect on patient health. Most patients retain their fertility, but the risk of infertility is likely to be increased by chemotherapy. Screening for gonadal dysfunction should be considered in the follow-up of testicular cancer survivors.

The Metabolic Syndrome and Disturbances in Hormone Levels in Long-Term Survivors of Disseminated Testicular Cancer

The metabolic syndrome may be an important risk factor for cardiovascular disease in long-term survivors of testicular cancer (TC). We investigated the associations between hormone levels and the metabolic syndrome in these men. We included TC patients cured by orchidectomy and cisplatin-based chemotherapy, stage I TC patients after orchidectomy only, and healthy men of comparable age. Presence of the metabolic syndrome was determined using guidelines from the National Cholesterol Education Program Adult Treatment Panel III. Thyroid-stimulating hormone, follicle-stimulating hormone (FSH), inhibin B, luteinizing hormone (LH), total testosterone, sex-hormone-binding globulin, free testosterone, estradiol, dehydroepiandrosterone sulfate, and insulin-like growth factor 1 were determined in blood. Cortisol metabolite excretion was measured in urine. Eighty-six chemotherapy patients (median follow-up, 7 years) were compared with 44 stage I patients and 47 controls. LH and FSH were higher, and inhibin B and total and free testosterone were lower in chemotherapy patients than controls. Adrenal and thyroid hormone production were unaffected. Chemotherapy patients with the metabolic syndrome (n = 22; 26%) had a higher body mass index (BMI) pretreatment, a larger BMI increase during follow-up, lower total testosterone, and higher urinary cortisol metabolite excretion than those patients without the metabolic syndrome. BMI and insulin were associated with the metabolic syndrome, while total testosterone and urinary cortisol metabolite excretion were associated with BMI. We found gonadal dysfunction, but normal adrenal and thyroid function. Through its association with BMI, testosterone may play a role in the development of the metabolic syndrome in long-term TC survivors.

Neurocognitive function (NCF) in long-term survivors of testicular cancer (TC)

8034 Background: Cisplatin-based chemotherapy (CBCT) regimens are standard treatment for TC, delivering long-term survival and cure rates. However, cisplatin is a neurotoxin with documented iatrogenic nervous system effects, including neuronal degeneration and myelin thinning. TC occurs primarily in men aged 15 to 35, coinciding with maturation of the frontal lobes and the continuing myelination extending through middle adulthood. Thus, CBCT occurs at a time of increased neurocognitive vulnerabilty and may impact NCF. Despite recent interest in the neurocognitive sequelae of chemotherapy, little is known about the effects of CBCT on NCF in TC survivors. Method: This study compared NCF between TC survivors who had completed either CBCT (n = 16) or localized treatment (LT; n = 7). NCF was assessed with a standard neuropsychological battery. Participants also completed measures of psychological distress, fatigue, and quality of life (QOL). Results: Men ranged in age from 23–64 years (M = 41), were at least 2.5 years post-diagnosis (M = 7.4), and were primarily college educated (78%). Demographics, psychological distress, fatigue, and QOL did not differ between treatment groups (all ps > .3). Compared to men who received LT, men treated with CBCT demonstrated poorer performance on two executive function measures, Stroop Interference (p = .028), and the Penn Conditional Exclusion Test (PCET: p = .008). Increased PCET errors were associated with poorer Functional QOL (p = .007). Psychological distress and fatigue were unrelated to NCF (all ps ≥ .2). Conclusions: Although preliminary, these data suggest that TC survivors treated with CBCT have mild deficits in NCF that impact QOL. Given the similarity of the treatment groups, and that NCF was unrelated to psychological distress or fatigue, the most likely mechanism is cisplatin associated neurotoxicity. Larger scale studies are needed to elucidate the mechanisms underlying NCF deficits in TC survivors and to explore the real-life impact of these deficits on QOL. No significant financial relationships to disclose.

Metabolic syndrome in long-term testicular cancer survivors

4576 Background: The purpose of this study was to investigate if treatment for testicular cancer (TC) increases the risk of metabolic syndrome (MetS) in long-term survivors of TC. Methods: 1264 patients, treated for unilateral TC during 1980–1994, were included in this study (1998–2002), including measurements of systolic (SBP) and diastolic (DBP) blood pressure, body mass index (BMI), blood tests and a questionnaire providing information about medical history. For the present analyses we excluded patients > 60 years at follow-up, leaving 1135 patients eligible. Patients were categorized in four treatment groups: Surgery (n=225), radiotherapy (RT, n=446), and two chemotherapy groups: Cumulative cisplatin dose ≤850 mg (n=376) and cumulative cisplatin dose >850 mg (cis>850, n=88). A healthy control group consisted of males from the Tromsø Population Study (n=1150). MetS was present if ≥ 2 of the following four components were present: Hypertension (SBP≥140 mmHg and/or DBP≥90 mmHg and/or use of antihypertensive medication); obesity (BMI≥30); hypercholesterolemia (total cholesterol ≥5.2 mmol/l and/or use of statins); diabetes mellitus. Results: Median observation time was 11.1 years (range 4–22). Median age at follow-up was 43 years (range 23–60). Age-adjusted logistic regression analyses were performed to compare the prevalence of MetS between treatment groups, using the surgery group as reference. The RT group did not differ from the surgery group, while both chemotherapy groups had significantly increased odds of MetS, highest for the cis>850 group (OR 2.8, 95% CI 1.6–4.7). When MetS was classified as ≥ 3 components present, only the cis>850 group differed from the surgery group (OR 2.6, 95% CI 1.1–6.0). The prevalence of MetS for the total patient group did not differ from that of healthy controls. Subgroup analysis showed that the cis>850 group had significantly increased odds of having MetS (OR 2.1, 95% CI 1.3–3.4), while the other treatment groups did not differ from healthy controls. Conclusion: Long-term TC survivors treated with cisplatin-based chemotherapy have a significantly increased risk of developing metabolic syndrome, compared to patients treated with other modalities or to healthy controls. No significant financial relationships to disclose.