One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group.

BACKGROUND: SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. PATIENTS AND METHODS: In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. RESULTS: At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. CONCLUSIONS: The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.

Sperm counts and endocrinological markers of spermatogenesis in long-term survivors of testicular cancer.

BACKGROUND: The objective of this study was to assess markers of spermatogenesis in long-term survivors of testicular cancer (TC) according to treatment, and to explore correlations between the markers and associations with achieved paternity following TC treatment. METHODS: In 1191 TC survivors diagnosed between 1980 and 1994, serum-follicle stimulating hormone (s-FSH; n=1191), s-inhibin B (n=441), and sperm counts (millions per ml; n=342) were analysed in a national follow-up study in 1998-2002. Paternity was assessed by a questionnaire. RESULTS: At median 11 years follow-up, 44% had oligo- (<15 millions per ml; 29%) or azoospermia (15%). Sperm counts and s-inhibin B were significantly lower and s-FSH was higher after chemotherapy, but not after radiotherapy (RT), when compared with surgery only. All measures were significantly more abnormal following high doses of chemotherapy (cisplatin (Cis)>850 mg, absolute cumulative dose) compared with lower doses (Cis ≤ 850 mg). Sperm counts were moderately correlated with s-FSH (-0.500), s-inhibin B (0.455), and s-inhibin B : FSH ratio (-0.524; all P<0.001). All markers differed significantly between those who had achieved post-treatment fatherhood and those with unsuccessful attempts. CONCLUSION: The RT had no long-term effects on the assessed markers of spermatogenesis, whereas chemotherapy had. At present, the routine evaluation of s-inhibin B adds little in the initial fertility evaluation of TC survivors.

Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case-parent triad study in a Norwegian-Swedish population.

BACKGROUND: Testicular germ cell tumour (TGCT) is the most common cancer in young men, and an imbalance between the estrogen and androgen levels in utero is hypothesized to influence TGCT risk. Thus, polymorphisms in genes involved in the action of sex hormones may contribute to variability in an individual's susceptibility to TGCT. METHODS: We conducted a Norwegian-Swedish case-parent study. A total of 105 single-nucleotide polymorphisms (SNPs) in 20 sex hormone pathway genes were genotyped using Sequenom MassArray iPLEX Gold, in 831 complete triads and 474 dyads. To increase the statistical power, the analysis was expanded to include 712 case singletons and 3922 Swedish controls, thus including triads, dyads and the case-control samples in a single test for association. Analysis for allelic associations was performed with the UNPHASED program, using a likelihood-based association test for nuclear families with missing data, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. False discovery rate (FDR) was used to adjust for multiple testing. RESULTS: Five genetic variants across the ESR2 gene [encoding estrogen receptor beta (ERß)] were statistically significantly associated with the risk of TGCT. In the case-parent analysis, the markers rs12434245 and rs10137185 were associated with a reduced risk of TGCT (OR = 0.66 and 0.72, respectively; both FDRs <5%), whereas rs2978381 and rs12435857 were associated with an increased risk of TGCT (OR = 1.21 and 1.19, respectively; both FDRs <5%). In the combined case-parent/case-control analysis, rs12435857 and rs10146204 were associated with an increased risk of TGCT (OR = 1.15 and 1.13, respectively; both FDRs <5%), whereas rs10137185 was associated with a reduced risk of TGCT (OR = 0.79, FDR <5%). In addition, we found that three genetic variants in CYP19A1 (encoding aromatase) were statistically significantly associated with the risk of TGCT in the case-parent analysis. The T alleles of the rs2414099, rs8025374 and rs3751592 SNPs were associated with an increased risk of TGCT (OR = 1.30, 1.30 and 1.21, respectively; all FDRs <5%). We found no statistically significant differences in allelic effect estimates between parental inherited genetic variation in the sex hormone pathways and TGCT risk in the offspring, and no evidence of heterogeneity between seminomas and non-seminomas, or between the Norwegian and the Swedish population, in any of the SNPs examined. CONCLUSIONS: Our findings provide support for ERß and aromatase being implicated in the aetiology of TGCT. Exploring the functional role of the TGCT risk-associated SNPs will further elucidate the biological mechanisms involved.

Long-term follow-up after risk-adapted treatment in clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT) implementing adjuvant CVB chemotherapy. A SWENOTECA study.

BACKGROUND: To offer minimized risk-adapted adjuvant treatment on a community and nationwide basis for patients with clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT). The aim was to reduce the risk of relapse and thereby reducing the need of later salvage chemotherapy while maintaining a high cure rate. PATIENTS AND METHODS: From July 1995 to January 1998, a total of 232 Swedish and Norwegian patients were treated for CS1 NSGCT. All were eligible for inclusion into one of two community-based multicenter Swedish and Norwegian Testicular Cancer Project (SWENOTECA) III studies. One study was a prospective randomized study for patients without vascular invasion in the testicular tumor (VASC-), evaluating the effect of one adjuvant course of cisplatin, vinblastine and bleomycin (CVB) compared with surveillance. The second study was a prospective study evaluating the effect of two adjuvant courses of CVB for VASC+ patients. RESULTS: Due to slow accrual and emerging data on toxicity of CVB, the studies were prematurely closed for inclusion in 1998. Of the 232 CS1 patients treated during the study period, only 97 were included in the studies. As all remaining patients were managed according to the SWENOTECA III protocol, although not randomized, the data were pooled. At a median follow-up of 10.1 years, there have been 24 relapses. While one course of CVB to VASC- patients had limited effect on the relapse rate, two courses of adjuvant CVB reduced the relapse rate among VASC+ patients by >90%. Toxicity was high in patients administered adjuvant CVB as 24% of patients experienced grade 3 or 4 obstipation/ileus and 23% grade 3 or 4 infection. CONCLUSIONS: There was no statistical difference in relapse rate between one course of adjuvant CVB and surveillance for VASC- NSGCT patients. Two courses of adjuvant CVB for VASC+ NSGCT patients reduced the relapse rate with >90% in comparison to the surveillance group. Toxicity was unacceptably high for all patients receiving CVB. Adjuvant CVB chemotherapy has no place in the treatment of CS1 NSGCT.

Blood pressure and body mass index in long-term survivors of testicular cancer.

PURPOSE: To evaluate blood pressure and body mass index (BMI) in long-term survivors of testicular cancer (TC) treated with different modalities. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Prognostic factors in unselected patients with nonseminomatous metastatic testicular cancer: a multicenter experience.

Between 1981 and 1986, 200 consecutive patients with metastatic nonseminomatous testicular cancer were entered into the Swedish Norwegian Testicular Cancer (SWENOTECA) project from 14 hospitals. The treatment plan was four chemotherapy cycles (cisplatin, vinblastine, and bleomycin) followed by surgical resection of residual tumor masses. After a median observation time of 75 months, the overall 5-year survival rate was 82%. In a univariate analysis, the following parameters influenced the prognosis significantly: the extent of the disease (Medical Research Council [MRC] grouping); the prechemotherapy levels of serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH); the patients' age; the presence of extrapulmonary hematogeneous metastases; and/or particularly large lymph node metastases. Patients fared better when more than 3 weeks elapsed between orchiectomy and start of chemotherapy as compared with those who were treated within this interval. The place of treatment (a large oncology unit v smaller units) also represented a significant prognostic factor for patients with large-volume (LV) and very-large-volume (VLV) disease combined. Multivariate analysis (Cox regression proportional hazards model) performed in all 193 assessable patients showed the following adverse prognostic factors: high-volume metastatic burden, age older than 35 years, prechemotherapy AFP greater than 500 micrograms/L and/or HCG greater than 1,000 U/L, and an interval between orchiectomy and start of chemotherapy of less than 3 weeks. The place of treatment also significantly influenced the final outcome. If patients with LV and VLV disease were combined, the presence of two of the following risk factors represented an additional prognostic factor: AFP greater than 1,000 micrograms/L, HCG greater than 10,000 U/L, liver metastases, brain metastases, bone metastases, retroperitoneal tumor greater than or equal to 10 cm, and mediastinal tumor greater than or equal to 5 cm.

Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish-Norwegian Testicular Cancer Group.

Between 1981 and 1986, 279 consecutive patients with clinical stage I (CS1) nonseminomatous germ cell tumors (NSGCT) of the testis underwent pathological staging (PS) with retroperitoneal lymphadenectomy (RPLND). Patients with retroperitoneal metastases (PS2) received adjuvant chemotherapy. The median follow-up time after RPLND was 50 months (range, 30 to 90). Clinical and histopathologic features were registered prospectively and analyzed for association with risk of having PS2, relapse despite pathological stage 1 (PS1) or the combined risk of either event, metastatic disease (MET). Seventy-five (26.9%) of the patients had PS2 disease, and 30 (14.7%) of the 204 PS1 patients relapsed, indicating that at least 105 (37.6%) of this CS1 population had subclinical MET at the time of orchiectomy. Four (1.4%) of the 279 CS1 patients died of testicular cancer. Multivariate analyses showed several variables to be significantly associated with outcome for the CS1 patients; vascular invasion in primary tumor and normal preorchiectomy serum alpha-fetoprotein (Pre-AFP) level indicated PS2 disease. If Pre-AFP was excluded from the model, the absence of teratoma or yolk sac elements in the primary tumor became significant predictors of PS2. Vascular invasion, absence of teratoma, and a short interval between orchiectomy and RPLND indicated increased risk of relapse in PS1 patients. Vascular invasion, normal Pre-AFP, absence of teratoma elements, and a short orchiectomy to RPLND interval were predictive of MET. Our results indicate that prognostic factors useful for stratification of CS1 patients with NSGCT to different treatment options may be established.

Treatment intention in hospitalized cancer patients in oncological wards in Norway: a national survey.

Clinicians often do not agree whether a treatment is given with a palliative or curative intent. A common clear definition does not exist. This study has assessed the usefulness of dividing the goal of treatment into three distinct categories: curative treatment; palliative, symptom preventive treatment; and palliative, symptom relieving treatment. In a cross-sectional study among all cancer centres in Norway, a total of 629 patients were included into the study. Of these patients, 60% received palliative treatment, with an equal distribution between symptom preventive and symptom relieving. The definitions were found easy to use by the physicians. It gave important information of differences between cancer diagnosis with respect to the number of patients receiving palliative treatment. In order to refine the classification system, the authors will, in future studies, include a fourth category, life prolonging treatment, which is located between curative and palliative treatment with respect to treatment intensity.

Weekly Adriamycin vs. 4-epidoxorubicin every second week in advanced breast cancer. A randomized trial. The Norwegian Breast Cancer Group.

One hundred and sixty-six patients with advanced breast cancer previously not treated with chemotherapy for metastatic disease were randomly allocated to 20 mg Adriamycin i.v. weekly (Awkly) as bolus injection or 50 mg 4-epidoxorubicin biweekly over a 3-h infusion time (EPIbiwkly). Of the 149 patients evaluable for response, the response rate was 36% for Awkly vs. 22% for EPIbiwkly (P = 0.10). There was no difference in response duration or survival. The main difference between the two regimens was in toxicity. Seventy per cent of Awkly patients virtually had no side-effects vs. 15% in the EPIbiwkly group. Significant differences in favour of Awkly were observed both for nausea/vomiting and alopecia.

Chemotherapy with or without high-dose medroxyprogesterone acetate in oestrogen-receptor-negative advanced breast cancer. Norwegian Breast Cancer Group.

In a randomised study 142 patients with advanced oestrogen-receptor-negative breast cancer in the tumour tissue received chemotherapy alone or chemotherapy combined with high doses (1000 mg daily) of oral medroxyprogesterone acetate (HD-MPA). Of the 126 fully evaluable for response, the response rates were 46% for chemotherapy alone and 73% for chemotherapy with HD-MPA (P = 0.005). There was no significant difference with regard to duration of response. Of the 138 patients evaluable for survival and toxicity, survival was shorter in the combined treatment group; median survival of 9 versus 13 months (P less than 0.05). Considerable toxicity was seen from HD-MPA, especially weight gain and fluid retention. The present study provides evidence that in concordance with preclinical studies an interaction between chemotherapy and HD-MPA may exist in breast cancer normally resistant to hormone therapy. The side-effects from MPA were substantial, however, and the survival data are of great concern.

The level of physical activity in long-term survivors of testicular cancer.

The aim of this study was to estimate the level of physical activity (LPA) in a large cohort of testicular cancer survivors (TCSs) and compare these results with observations from men in the same age range in the general population (GenPop). We also wanted to identify parameters that influenced physical activity. The study populations consisted of 1276 TCSs treated with surgery, radiotherapy or chemotherapy with or without surgery (mean observation time was 12 years), and 20391 male inhabitants from a Norwegian county (GenPop). All completed a question investigating two sub-levels of physical activity. The logistic regression analysis adjusting for different covariates, showed significantly more physically active men among the TCSs compared with the GenPop (43 versus 37%) (adjusted odds ratio (aOR)=1.32 (95% Confidence Interval (CI) 1.10-1.58)). The results indicate that the experience of testicular cancer increases rather than reduces the LPA in TCSs, independent of treatment given.

Knowledge of and attitudes toward complementary and alternative therapies; a national multicentre study of oncology professionals in Norway.

This study reports on oncology professionals' knowledge and attitude toward complementary and alternative medicines (CAM), classified according to their primary application as complementary or alternative methods. In June 2002, we conducted a national, multicentre survey of 828 Norwegian oncologists, nurses, clerks and therapeutic radiographers. A response rate of 61% was achieved. Only a few physicians (4%) described their reactions to alternative medicine as positive compared with nurses (33%), therapeutic radiographers (32%) and clerks (55%) (P<0.0001). Females showed a more positive view than males (33% versus 14%, P<0.0001). More participants expressed a positive attitude to complementary versus alternative medicines. Most respondents regarded healing by hand or prayer, homeopathy, and Iscador (mistletoe) as alternative therapies. In contrast, most respondents classified acupuncture, meditation, reflexology, music/art-therapy, aromatherapy and massage as complementary therapies. This survey demonstrates major differences, by gender as well as oncology health profession in views about and the classification of various CAM methods.

Phase II trial of anaxirone (TGU) in advanced colorectal cancer: an EORTC Early Clinical Trials Group (ECTG) study.

Anaxirone, a rationally synthesised triepoxide derivative, was given to 46 patients with metastatic colorectal cancer. Good risk patients received 800 mg/m2 as a rapid intravenous injection every 4 weeks, whereas poor risk patients received 650 mg/m2. Of 46 patients, 45 were evaluable for toxicity and 42 for efficacy analysis. There were 37/45 patients with poor risk, showing no difference in toxicity as compared to good risk patients. The major toxic effect was myelosuppression with 34% of all patients experiencing grade 3 or 4 leucopenia; thrombocytopenia was less frequent. Locoregional phlebitis occurred in 66% of the patients. There was no objective tumour response to anaxirone in 42 evaluable patients. Only 4 patients achieved stabilisation of the disease lasting maximally up to 248 days. Anaxirone is inactive in metastatic colorectal cancer.

Risk-adapted treatment of clinical stage 1 non-seminoma testis cancer.

250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.

Toxicity in long-term survivors after adriamycin containing chemotherapy of malignant germ-cell tumors.

In order to assess overall treatment-induced long-term morbidity after high-dose adriamycin-based chemotherapy +/- radiotherapy, clinically significant toxicity was studied in survivors after treatment of advanced germ-cell cancer who had received adriamycin-containing chemotherapy before cisplatin became available in Norway. Most of the patients were also irradiated. The study comprises 47 patients with advanced germ-cell cancer who survived for at least 5 years after chemotherapy containing adriamycin (VACAM: vincristine, adriamycin, cyclophosphamide, actinomycin-D and medroxyprogesterone acetate) as part of their primary systemic treatment (before 1978) or as maintenance chemotherapy after initial cisplatin-based cytotoxic treatment (after 1978). Thirty-two patients also had radiotherapy. The median follow-up was 12.3 years. Forty-one events of late toxicities were recorded in 25 patients, 37 of these were observed after combined radiotherapy and chemotherapy. The most frequent late side effects were cardiotoxicity, gastrointestinal toxicity and neurological disorders observed in 7, 12 and 8 patients, respectively. Three patients who were irradiated to the cardiac region, died of heart failure. Secondary solid cancer developed in 7 patients after a median follow-up of 10.5 years (relative risk 4.8, 95% confidence interval 1.9 to 9.9). In a historical perspective high-dose adriamycin-containing combination chemotherapy if applied with cyclophosphamide and/or radiotherapy, may occasionally be curative in selected patients with advanced germ cell tumours, but leads to an unacceptable high incidence of severe cardiac, gastrointestinal and neurological late side effects. The present follow-up study highlights that such treatment should be avoided in the curatively intended treatment of cancer patients and emphasizes the need of long-term follow-up studies in surviving cancer patients.

Digitoxin medication and cancer; case control and internal dose-response studies.

BACKGROUND: Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population. METHODS: Computer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases. RESULTS: The population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer. An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract. CONCLUSION: Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease. These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents.

PharmCalc: program for the calculation of clinical pharmacokinetic parameters of methotrexate.

A new program package (PharmCalc) has been developed for the calculation of basic pharmacokinetic parameters (half-time, systemic clearance, renal clearance, AUC, volume of distribution, CSF/serum distribution ratio) of methotrexate (MTX). The program helps in the early recognition of patients at risk for toxicity and calculates the dosage of folinic acid rescue adjusted to the serum levels of MTX. The program offers a standardized and automated evaluation procedure for MTX pharmacokinetics and provides an easy-to-use tool for further research in this field. The concept and routines of the program are described.

Serum tumour markers in testicular and extragonadal germ cell malignancies.

Serum tumour marker analyses are now an integral part of the modern management of patients with testicular or extragonadal germ cell tumours of the testis. AFP, HCG and may help in the diagnosis of extragonadal germ cell tumours in (young) males with malignancies of uncertain origin. AFP and HCG analyses play decisive roles in the classification, staging, choice of therapy and monitoring of treatment and follow-up of patients with nonseminomatous germ cell tumours. HCG, LDH and possibly NSE analyses are becoming important tools for the management of advanced seminoma, but there is a need for more reliable markers in this tumour type. Serum samples for AFP and HCG should be obtained before orchiectomy in any patient with a testicular tumour, as the pre-orchiectomy titres may represent important information for the subsequent clinical decision making. Cost-benefit estimates regarding the role of serum tumour markers in saving the life of patients with testis cancer are presented.

Predicted cardiovascular mortality and reported cardiovascular morbidity in testicular cancer survivors.

INTRODUCTION: We examined if testicular cancer (TC) treatment is associated with any risk for cardiovascular morbidity or predicted mortality according to the SCORE model, in which a 10-year future risk of >or=5% for developing a fatal cardiovascular event qualify for high-risk status. METHODS: One thousand one hundred thirty-four TC survivors treated 1980-1994 participated in this study (1998-2002). Patients were categorised in four treatment groups: surgery (n = 225), radiotherapy (n = 445), and two chemotherapy groups: cumulative cisplatin dose 850 mg (cis>850, n = 89). Patients with cardiovascular disease, diabetes or SCORE >or=5% constituted a high-risk group, and those with SCORE >1% an intermediate/high risk group. RESULTS: Age-adjusted mean SCORE was 0.93% for the surgery group. In comparison, chemotherapy treated patients had significantly higher SCORE (1.07%, p = 0.01). Only 15% of patients were scored to be at high-risk, while 53% qualified for the intermediate/high risk group. Patients in the cis>850 group had increased odds for having intermediate/high risk, compared with the surgery group (OR 3.4, 95% CI 1.3-8.7). Only 23 cardiovascular events had occurred since the testicular cancer diagnosis. CONCLUSION: The SCORE model indicates that patients treated with cisplatin-based chemotherapy have a significantly increased future risk of a fatal cardiovascular event. IMPLICATIONS FOR CANCER SURVIVORS: TC survivors should be followed regularly with respect to cardiovascular risk profile beyond the routine 10-year clinical follow-up.

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

BACKGROUND: 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. PATIENTS AND METHODS: 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) 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. RESULTS: 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. CONCLUSION: 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.