Quantitative ultrasound of the calcaneus (QUS): A valuable tool in the identification of patients with non-metastatic prostate cancer requiring screening for osteoporosis.

Non-metastatic prostate cancer (PCa) patients are at increased risk for osteoporosis and fractures mainly due to androgen deprivation therapy (ADT)-associated hypogonadism, but this remains largely underdiagnosed and untreated. In this study, we examine the value of pre-screening calcaneal QUS in identifying patients who should be referred for screening for osteoporosis using dual-energy X-Ray absorptiometry (DXA). In a single-center retrospective cross-sectional cohort study, we analysed data on DXA and calcaneal QUS measurements systematically collected between 2011 and 2013 in all non-metastatic PCa patients attending our Uro-Oncological Clinic at the Leiden University Medical Center. Receiver operating characteristic curves were used to assess the positive (PPV) and negative (NPV) predictive values of QUS T-scores of 0, -1.0, and - 1.8 in identifying DXA-diagnosed osteoporosis (T-scores ≤ - 2.5 and ≤ -2) at lumbar spine and/or femoral neck. Complete sets of data were available in 256 patients, median age 70.9 (53.6-89.5) years; 93.0 % had received local treatment, 84.4 % with additional ADT. Prevalence of osteoporosis and osteopenia was respectively 10.5 % and 53 %. Mean QUS T-score was -0.54 ± 1.58. Whereas PPV at any QUS T-score was <25 %, precluding the use of QUS as surrogate for DXA in screening for osteoporosis, QUS T-scores of -1.0 to 0.0 had a NPV of ≥94.5 % for DXA T-scores ≤ 2.5 and ≤ -2 at any site, confidently identifying patients least likely to have osteoporosis, thereby significantly reducing the number of patients requiring DXA screening for diagnosing osteoporosis by up to two-third. Osteoporosis screening is a significant unmet need in non-metastatic prostate cancer patients treated with ADT, and QUS may represent a valuable alternative pre-screening strategy to overcome logistics, time demands, and economic barriers encountered with current strategies for osteoporosis screening in these patients. Summary: Osteoporosis and associated increased fracture risk are common in non-metastatic prostate carcinoma, mainly due to androgen deprivation therapy, but these often remain underdiagnosed and untreated. We demonstrate that QUS is a safe, less costly pre-screen tool that reduces by up to two-third the number of patients requiring referral for DXA for osteoporosis screening.

Changes in bone mineral density in newly diagnosed testicular cancer patients after anticancer treatment.

CONTEXT: Patients with germ cell tumors (GCTs) have an excellent prognosis but are at risk for silent fractures. Data on bone mineral density (BMD) after anticancer treatment are scarce. OBJECTIVE: The objective of the study was BMD monitoring in GCT patients treated with or without chemotherapy. DESIGN: We prospectively studied 63 newly diagnosed GCT patients with a median age of 33 years (range 16-70 y) within 3 months of unilateral orchidectomy. Twenty-seven patients (42.9%) had no metastases. Thirty-six patients (57.1%) with metastatic disease received combination chemotherapy. SETTING: This study was conducted at the outpatient clinic of a single academic institution. INTERVENTIONS: We performed dual-energy X-ray absorptiometry scans and collected blood samples on a yearly basis, before and up to 5 years after anticancer treatment. MAIN OUTCOME MEASURES: Changes in total hip and lumbar spine BMD, serum concentrations of gonadal hormones, and bone turnover markers were measured. RESULTS: BMD remained normal in stage I patients. In patients with metastatic disease, a significant decrease in lumbar spine BMD (-1.52%; P = .004) and total hip BMD (-2.05%; P < .0001) was observed 1 year after chemotherapy and remained stable thereafter for up to 5 years. There was no significant relationship between the observed decrease in BMD and gonadal status, vitamin D status, or cumulative dose of cisplatin or (antiemetic) corticosteroids. CONCLUSIONS: Metastatic GCT survivors demonstrate significant bone loss within the first year after curative combination chemotherapy, with no recovery up to 5 years after anticancer treatment. Whether this bone loss is associated with increased fracture risk and whether this could be prevented by bone modifying treatment remains to be established.

Chemotherapy for testicular cancer induces acute alterations in diastolic heart function.

BACKGROUND: After treatment with cisplatin-based chemotherapy for testicular cancer (TC), patients have higher prevalence of cardiovascular complications after long-term follow up. Little is known about acute cardiovascular effects of cisplatin-based chemotherapy. The aim of this study was to explore acute effects of chemotherapy on cardiac function in patients treated for TC. METHODS: Fourteen TC patients (age 34.6 ± 12.3 years) were studied before and 3 months after start with cisplatin-based chemotherapy. Cardiac function was assessed with magnetic resonance imaging. Fasting glucose and insulin levels were measured and insulin sensitivity, reflected by the quantitative insulin sensitivity index (Quicki index), was calculated. RESULTS: Left ventricular (LV) end-diastolic volume and LV stroke volume (SV) significantly decreased from 192 ± 27 to 175 ± 26 ml (P<0.05) and 109 ± 18 to 95 ± 16 ml (P<0.05), respectively. The ratio of early and atrial filling velocities across the mitral valve, a parameter of diastolic heart function, decreased after chemotherapy from 1.87 ± 0.43 to 1.64 ± 0.45 (P<0.01). Metabolic parameters were unfavourably changed, reflected by a decreased Quicki index, which reduced from 0.39 ± 0.05 to 0.36 ± 0.05 (P<0.05). CONCLUSION: Chemotherapy for TC induces acute alterations in diastolic heart function, paralleled by unfavourable metabolic changes. Therefore, early after chemotherapy, metabolic treatment may be indicated to possibly reduce long-term cardiovascular complications.

Prevalence of the metabolic syndrome and cardiovascular disease risk in chemotherapy-treated testicular germ cell tumour survivors.

BACKGROUND: Testicular cancer patients have an increased risk for cardiovascular disease (CVD), which might be related to the increased prevalence of the metabolic syndrome (MetS) in this group of patients. METHODS: We assessed the prevalence of MetS and calculated the 10-year CVD risk in a cohort of 255 testicular germ cell tumour survivors (median age, 38.7 years; interquartile range, 31-48) at a mean of 7.8 years after anti-cancer treatment, and compared these with data obtained from 360 healthy men. RESULTS: Survivors had an age-adjusted increased risk for MetS of 1.9 compared with that of healthy controls. The risk for MetS was highest in survivors treated with combination chemotherapy (CT) 2.3 (Adult Treatment Panel of the National Cholesterol Education Program classification) and 2.2 (International Diabetes Federation classification). The risk of MetS was especially increased in survivors with testosterone levels in the lowest quartile (OR, 2.5). Ten-year cardiovascular risk as assessed by the Framingham Risk Score (3.0%) and Systemic Coronary Risk Evaluation (1.7%) algorithms was low, independent of treatment, and was comparable to controls. CONCLUSION: Testicular germ cell tumour survivors have an increased prevalence of MetS, with hypogonadism and CT treatment being clear risk factors for the development of the syndrome. The increased prevalence of MetS was not associated with an increased 10-year cardiovascular risk.

Prevalence of vertebral fractures independent of BMD and anticancer treatment in patients with testicular germ cell tumors.

CONTEXT: The prognosis of testicular germ cell tumors (GCT) is excellent, and survival of GCT patients has significantly increased. However, skeletal morbidity may potentially be increased in these patients due to chemotherapy-associated hypogonadism. OBJECTIVE: Our objective was assessment of skeletal fragility in testicular GCT patients. DESIGN AND SETTING: We conducted a cross-sectional study in long-term survivors and newly diagnosed patients at a single center with recruitment over a 2-yr period. PATIENTS AND METHODS: We studied 199 cured long-term survivors of GCT, a mean of 7.4 yr after unilateral orchidectomy, and 45 newly diagnosed patients within 3 months of unilateral orchidectomy but before anticancer treatment. Bone mineral density (BMD) measurements were performed, and the presence of vertebral fractures (VF) was assessed in lateral thoracolumbar x-rays of the spine using the Genant's semiquantitative method. RESULTS: Sixty-three patients (25.8%) had Z-scores between -1 and -2 sd, and 12 patients (5.7%) had Z-scores below -2 sd. Moderate and severe VF (grade 2 or higher) were observed in 13.6% of cured long-term survivors and in 15.6% of newly diagnosed patients. Including mild (grade 1) VF, the prevalence was 40.2 and 31.1%, respectively. There was no relationship between severity or number of VF and age, tumor type, staging, previous chemotherapy, gonadal status, vitamin D levels, or BMD values. CONCLUSION: We identify a relatively high prevalence of mild to moderate VF independently of BMD or previous chemotherapy in long-term survivors and in newly diagnosed patients with GCT. Although the pathogenesis of these fractures remains unclear, their presence represents a potential cause of skeletal morbidity in otherwise healthy survivors of testicular GCT.