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SUMMARY: Objectives: The primary objective of this feasibility study was to identify quality of life (QoL) scores and symptom scales as tools for measuring patient‐reported outcomes (PRO) associated with haemoglobin level in chemotherapy‐treated cancer patients. Secondary objectives included comparing QoL and symptoms between randomisation arms. Background: Anaemia in cancer patients undergoing chemotherapy is associated with decreased QoL. One treatment option is red blood cell transfusion (RBCT). However, the optimal haemoglobin trigger for transfusion is unknown. Methods: Patients were randomised to a haemoglobin trigger for RBCT of either < 9·7 g dL−1 (arm A) or < lower normal level, female: 11·5 g dL−1, male: 13·1 g dL−1 (arm B). Four PROs were used: Functional Assessment of Cancer Therapy‐General (FACT‐G) and the FACT‐Anaemia (FACT‐An), a Numeric Rating Scale on symptoms of anaemia and self‐reported Performance Status (PS). The association between haemoglobin and PRO variables was assessed using a linear mixed model with random effects. Results: A total of 133 patients were enrolled, of which 86 patients received RBCT (28 in arm A, 58 in arm B). Baseline questionnaires were filled out in 79·7% of cases. Haemoglobin levels were significantly correlated with FACT‐An, FACT‐An Total Outcome Index (TOI), Functional Well‐Being, fatigue and PS. Improvement on several PRO variables was observed in both arms after RBCT, with clinically minimal important differences observed in FACT‐G, Physical Well‐Being, FACT‐An, FACT‐An TOI, fatigue and dyspnoea. Conclusions: QoL scores of physical and functional domains as well as self‐reported anaemia‐related symptoms correlated well with haemoglobin level in chemotherapy‐treated cancer patients. [ABSTRACT FROM AUTHOR]

Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover. In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): −0.01 − 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: −0.01–0.03), BMD of the left femoral neck: 0.00, (95% CI: −0.01–0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX. 12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort. [ABSTRACT FROM AUTHOR]

BACKGROUND In a phase 2 study, rucaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), showed a high level of activity in patients who had metastatic, castration-resistant prostate cancer associated with a deleterious BRCA alteration. Data are needed to confirm and expand on the findings of the phase 2 study. METHODS In this randomized, controlled, phase 3 trial, we enrolled patients who had metastatic, castration-resistant prostate cancer with a BRCA1, BRCA2, or ATM alteration and who had disease progression after treatment with a second-generation androgen-receptor pathway inhibitor (ARPI). We randomly assigned the patients in a 2:1 ratio to receive oral rucaparib (600 mg twice daily) or a physician’s choice control (docetaxel or a second-generation ARPI [abiraterone acetate or enzalutamide]). The primary outcome was the median duration of imaging-based progression-free survival according to independent review. RESULTS Of the 4855 patients who had undergone prescreening or screening, 270 were assigned to receive rucaparib and 135 to receive a control medication (intention-to-treat population); in the two groups, 201 patients and 101 patients, respectively, had a BRCA alteration. At 62 months, the duration of imaging-based progression-free survival was significantly longer in the rucaparib group than in the control group, both in the BRCA subgroup (median, 11.2 months and 6.4 months, respectively; hazard ratio, 0.50; 95% confidence interval [CI], 0.36 to 0.69) and in the intention-to-treat group (median, 10.2 months and 6.4 months, respectively; hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001 for both comparisons). In an exploratory analysis in the ATM subgroup, the median duration of imaging-based progression-free survival was 8.1 months in the rucaparib group and 6.8 months in the control group (hazard ratio, 0.95; 95% CI, 0.59 to 1.52). The most frequent adverse events with rucaparib were fatigue and nausea. CONCLUSIONS The duration of imaging-based progression-free survival was significantly longer with rucaparib than with a control medication among patients who had metastatic, castration-resistant prostate cancer with a BRCA alteration. [ABSTRACT FROM AUTHOR]

• This ESMO Clinical Practice Guideline provides key recommendations on the management of testicular seminoma and non-seminoma. • Authorship includes a multidisciplinary group of experts from different institutions and countries in Europe. • Key treatment recommendations are provided. • Recommendations are based on available scientific data and the authors' collective expert opinion. [ABSTRACT FROM AUTHOR]

Carcinoma in situ testis (CIS) is known as the precursor of germ cell cancer of the testis. International guidelines on diagnosis and treatment are inconsistent. Some countries offer routine biopsies of the contralateral testicle in relation to orchidectomy for testicular cancer, whereas other countries only offer this to high-risk patients. The treatment options range from orchidectomy and chemotherapy to radiotherapy and in rare cases surveillance. Results of the different treatment strategies are presented in this review. The optimal radiation dose is still not clarified. Most patients have been treated in the dose range of 16-20 Gy. Higher doses involve a higher risk of androgen insufficiency. Radiotherapy is recommended in patients with contralateral CIS. Orchidectomy should be offered in extragonadal germ cell cancer and CIS in one testicle, whereas patients with bilateral CIS should be offered radiation therapy. Patients who have undergone chemotherapy for testicular cancer are still at risk of developing CIS and we also recommend radiotherapy to the affected testicle in these patients. Cryopreservation should be offered before treatment is initiated and all patients should have their androgen status measured on a regular basis to find those cases where hormone substitution is needed. [ABSTRACT FROM AUTHOR]

Study Question: Is anogenital distance (AGD) shorter in testicular cancer (TC) survivors than in men from the general population, and is AGD affected by testosterone replacement therapy in adulthood?Summary Answer: AGD, measured as distance from anus to scrotum (AGDas), is shorter in TC survivors and does not change as a result of testosterone replacement therapy.What Is Known Already: Animal studies have shown that AGD is a postnatal 'read-out' of foetal androgen action, and short AGD in male offspring is considered a sign of feminization caused by in utero disruption of the reproductive system. Likewise, measurement of AGD in human studies has suggested AGD to be part of the testicular dysgenesis syndrome hypothesis, which proposes that male reproductive disorders, such as hypospadias, cryptorchidism, some cases of impaired semen quality and TC, all share a common foetal origin.Study Design, Size, Duration: The aim was to assess AGD in men with a history of TC and controls, and furthermore to examine AGD during testosterone replacement therapy in adulthood. Study participants were TC survivors with a mild Leydig cell insufficiency who participated in a randomized double-blind study of testosterone replacement therapy versus placebo for 52 weeks (N = 69). Men from the general population were prospectively included from a study on testicular function as controls (N = 67).Participants/materials, Setting, Methods: We measured two variants of AGD; as our primary outcome the anoscrotal distance (AGDas) measured from the centre of the anus to the posterior base of the scrotum, and secondarily the anopenile distance (AGDap) measured from the anus to the cephalad insertion of the penis. Using multiple regression analysis, the mean difference in AGD between TC survivors and men from the general population was assessed, adjusted for height, BMI and examiner. Next, AGD was measured before and after 52 weeks of treatment with testosterone or placebo, and with covariance analysis differences between the two groups at follow-up was assessed after adjustment for baseline AGD, examiner, BMI and change in BMI during treatment.Main Results and the Role Of Chance: TC survivors had a shorter AGDas (-0.84 cm, 95% CI: -1.31; -0.37) compared to men from the general population, and AGDas did not differ between the testosterone and placebo treated group at follow-up (0.11 cm, 95% CI: -0.22; 0.44). In contrast, AGDap was not shorter in TC survivors after adjustment (0.05 cm, 95% CI: -0.30; 0.39), and was 0.48 cm longer (95% CI: 0.13; 0.82) at follow-up in the testosterone treated compared to the placebo-treated group.Limitations, Reasons For Caution: A limitation of the study is that the number of included men was limited, and results need confirmation in a larger study. Furthermore, TC survivors were significantly older than controls. For the comparison of AGD in TC survivors and controls, it was not possible to conduct the examinations with the examiner being blinded to which group he was examining, and it cannot be excluded that this can cause a bias.Wider Implications Of the Findings: The shorter AGDas in TC survivors compared to controls, which did not change upon adult testosterone replacement therapy, supports the hypothesis that reduced AGD is part of the testicular dysgenesis syndrome and may be a marker of disrupted foetal testicular development. By contrast, AGDap was not shorter in TC survivors and might be modestly sensitive to adult testosterone treatment, and thus inferior to AGDas as a constant postnatal marker of the foetal androgen environment.Study Funding/competing Interest(s): Expenses were paid by the Department of Oncology, Copenhagen University Hospital, Rigshospitalet. Kiowa Kirin International covered expenses for Tostran and placebo. The Danish Cancer Society, The Danish Cancer Research Foundation, the Preben & Anna Simonsen Foundation, and Rigshospitalet have supported the study. L.P. was financed by the Research Fund of the Capital Region of Denmark. The authors have no competing interests.Trial Registration Number: Part of the study is based on men participating in a randomized controlled trial registered at ClinicalTrials.gov, NCT02991209, 25 November 2016. [ABSTRACT FROM AUTHOR]

Summary: A simple histological method to evaluate the Leydig cell compartment is lacking. We aimed to establish such a method and to investigate if Leydig cell hyperplasia of the biopsy contralateral to the tumour‐bearing testicle in patients with testicular germ cell cancer is associated with biochemical signs of Leydig cell dysfunction after long‐term follow‐up. A case group of 50 long‐term testicular germ cell cancer survivors without human chorionic gonadotropin elevation, 10 testicular germ cell cancer patients with elevated human chorionic gonadotropin and 10 controls without testicular malignancy were included. For each subject, 2–4 representative sections from their testicular biopsies were selected for analysis. Using the image processing program ImageJ (V.1.48, NIH), an area with a minimum of 50 tubules was selected and delineated (total selected area) and the total Leydig cell area was calculated by adding up every delineated Leydig cell group within the total selected area. Four different methods were tested for the ability to quantify the Leydig cell compartment. In the 50 testicular germ cell cancer survivors, associations between the area of the Leydig cell compartment and serum levels of testosterone and luteinising hormone were investigated using linear regression analysis. The Leydig cell compartment was best quantified by the total Leydig cell area/total selected area index, which was significantly larger in the human chorionic gonadotropin‐positive patients than in controls (P = 0.00001). In the 50 human chorionic gonadotropin‐negative testicular germ cell cancer survivors, increasing total Leydig cell area/total selected area was significantly associated with decreased levels of total testosterone and decreased total testosterone/luteinising hormone ratio after a median of 9‐year follow‐up. In conclusion, a new simple method, total Leydig cell area/total selected area, was established to estimate the Leydig cell compartment in testicular biopsies. The index identified Leydig cell hyperplasia in the contralateral biopsy in patients with testicular germ cell cancer, and it was associated with long‐term biochemical Leydig cell dysfunction. Although in testicular germ cell cancer survivors, the clinical value is limited because the contralateral biopsies are not commonly available, we propose a closer andrological follow‐up in any patient with an increased total Leydig cell area/total selected area index. [ABSTRACT FROM AUTHOR]

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3–5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript. [ABSTRACT FROM AUTHOR]

Background: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. Patients and methods: Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. Results: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P=0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). Conclusions: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%. [ABSTRACT FROM AUTHOR]

Background Twenty to thirty percent of testicular cancer (TC) survivors have elevated serum levels of luteinising hormone (LH) with or without corresponding low testosterone levels (Leydig cell dysfunction) during clinical follow-up for TC. However, it remains to be clarified if this subgroup of TC survivors has an increased long-term risk of systemic inflammation and metabolic syndrome (MetS) when compared with TC survivors with normal Leydig cell function during follow-up. Patients and methods TC survivors with Leydig cell dysfunction and a control group of TC survivors with normal Leydig cell function during follow-up were eligible for participation in the study. Markers of systemic inflammation and prevalence of MetS were compared between TC survivors with Leydig cell dysfunction and the control group. Results Of 158 included TC survivors, 28 (18%) had uncompensated Leydig cell dysfunction, 59 (37%) had compensated Leydig cell dysfunction and 71 (45%) had normal Leydig cell function during follow-up. MetS and markers of systemic inflammation were evaluated at a median follow-up of 9.7 years (interquartile range 4.1–17.1) after TC treatment. The prevalence of MetS was significantly lower among patients with compensated Leydig cell dysfunction during follow-up (12% versus 27%, p = 0.04), whereas there was no difference between TC survivors with uncompensated Leydig cell dysfunction and controls (33% versus 27%, p = 0.5). Apart from high-sensitivity C-reactive protein which was higher in TC survivors with uncompensated Leydig cell dysfunction during follow-up, there was no evidence of increased systemic inflammation in patients with Leydig cell dysfunction during clinical follow-up. Total testosterone at follow-up was significantly associated with MetS, whereas there was no association between LH and MetS. Conclusion We did not find evidence that TC survivors with Leydig cell dysfunction during clinical follow-up had increased long-term risk of MetS. Total testosterone at follow-up was significantly associated with MetS. The study is registered at www.clinicaltrials.gov NCT02240966 . [ABSTRACT FROM AUTHOR]

Testicular cancer survivors have impaired gonadal function and increased risk of metabolic syndrome when compared to healthy controls. However, because of the fetal etiology of testicular cancer, familial unrelated healthy men might not be an optimal control group. The objective of this study was to clarify if testicular cancer survivors have impaired gonadal function and increased risk of metabolic syndrome when compared to their biological brothers. A cross-sectional study of testicular cancer survivors (ClinicalTrials.gov number, NCT02240966) was conducted between 2014 and 2016. Of 158 testicular cancer survivors included, 24 had a biological brother who accepted to participate in the study. Serum levels of reproductive hormones and prevalence of metabolic syndrome according to International Diabetes Federation Criteria and National Cholesterol Education Program (Adult Treatment Panel III) criteria comprised the main outcome measures of the study. Median age was similar in testicular cancer survivors and their biological brothers [44 years (IQR 39-50) vs. 46 (40-53) years respectively ( p = 0.1)]. In testicular cancer survivors, follow-up since treatment was 12 years (7-19). Serum levels of luteinizing hormone and follicle-stimulating hormone were elevated ( p ≤ 0.001), while total testosterone, free testosterone, inhibin B and anti-Müllerian hormone were lower ( p ≤ 0.001) in testicular cancer survivors than in their biological brothers. The prevalence of metabolic syndrome was similar and apart from HDL-cholesterol, which was lower in testicular cancer survivors ( p = 0.01); there were no differences in the individual components of the metabolic syndrome between testicular cancer survivors and their brothers. In conclusion, gonadal function was impaired in testicular cancer survivors, while we did not detect any difference in the prevalence of metabolic syndrome between testicular cancer survivors and their biological brothers. [ABSTRACT FROM AUTHOR]

Background: Bone metastases (BM) are rare in germ cell tumor (GCT) patients. Systematic data on risk factors, treatment and outcome are largely lacking. Patients and methods: A database created by an international consortium including 123 GCT patients with BM at primary diagnosis was retrospectively analysed. Survival estimates were calculated by the method of Kaplan-Meier and compared by log-rank testing. Cox regression analysis was applied for risk factor analyses. Results: In our cohort of patients, BM at primary diagnosis more often affected multiple sites (61%) and BM as the only metastatic site were scarce (9%). Histology was non-seminoma in 77% and seminoma in 23% of patients. After a median followup of 18 months (range, 0-228), estimated median PFS and OS were 21 (range, 0-225) and 98 months (95%CI, 36-160), respective 2-year PFS and OS rates were 34% and 45%. Negative prognosticators in univariate analysis were a mediastinal primary (PFS; HR 1.92; 95%CI, 1.05-3.50; OS; HR 2.16; 95%CI, 1.14-4.09) and the presence of liver and/or brain metastases (PFS; HR 1.89; 95%CI, 1.13-3.17; OS; HR 1.91; 95%CI, 0.024) Seminomatous histology was the strongest predictor for favorable PFS (multivariate Cox regression; HR, 0.32; P=0.011) with respective 2-year PFS and OS rates of 68% and 75% compared with 24% and 36% for nonseminoma patients. Conclusions: Outcome of GCT patients with primary metastatic bone disease is particularly poor in non-seminoma patients, even worse than the expected outcomes of the general IGCCCG 'poor prognosis' group. This series does not indicate that mutlimodal treatment improves the prognosis over stage-adapted chemotherapy alone, however, the statistical power of these results is limited due to low patient numbers in each specific subgroup. [ABSTRACT FROM AUTHOR]

The article focuses on a study regarding the effects of chemotherapy and resistance training in patients of germ cell cancer, and mentions that cisplatin-based chemotherapy show improvement in testicular germ cell cancer (GCC). Topics discussed include exclusion criteria for patients based on the evidence of cardiovascular and chronic disease.

Results concerning treatment of Testicular Germ Cell Cancer ( TGCC) and subsequent risk of testosterone deficiency are conflicting. To systematically evaluate and estimate the risk of testosterone deficiency ( TD) in TGCC-patients according to treatment to optimize follow-up and for prevention of late effects related to hypogonadism. We performed a critical review of PubMed in January 2015 according to the Preferred Reporting Items for Systematic Review and Meta-analysis ( PRISMA) statement. Twelve publications were selected for inclusion in this analysis. Eleven studies evaluated the risk of TD in TGCC-patients treated with standard chemotherapy ( CT) and the odds ratio for TD was 1.8 (95% CI) (1.3-2.5), ( p = 0.0007). Seven studies evaluated the risk of TD in TGCC-patients treated with non-conventional therapy and the odds ratio for TD was 3.1 (95% CI) (2.0-4.8), ( p < 0.0001). Six studies evaluated the risk of TD in TGCC-patients treated with infradiaphragmatic radiotherapy ( RT), and the odds ratio for TD was 1.6 (95% CI) (1.0-2.4), ( p = 0.03). In all treatment groups the risk of TD was compared with TGCC-patients treated with orchiectomy alone. There was no indication of heterogeneity between studies in the three treatment groups. Strong evidence exists that standard CT, non-conventional therapy and infradiaphragmatic RT are associated with an increased risk of TD in TGCC-patients when compared with orchiectomy alone. The risk of testosterone defficiency appears to be highest in patients treated with non-conventional therapy. [ABSTRACT FROM AUTHOR]

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. [ABSTRACT FROM AUTHOR]

Background: Screening programmes for contralateral carcinoma in situ (CIS) testis in patients with unilateral germ-cell cancer (GCC) have never been evaluated. We investigated the effect of screening for contralateral CIS in a large nationwide, population-based study. Patients and methods: A contralateral single-site biopsy was offered to 4130 patients in whom GCC had been diagnosed in 1984-2007 (screened cohort); 462 patients in whom GCC was diagnosed in 1984-1988 comprised the unscreened cohort. Cases with CIS were offered radiotherapy. Initially CIS-negative biopsies in patients with metachronous GCC were revised according to today's standards. Risk for metachronous GCC was estimated using cumulative incidence and the Cox proportional hazards model. Results: In the screened cohort, contralateral CIS was found in 181 (4.4%) patients. The cumulative incidence of metachronous GCC after 20 years was 1.9% in the screened cohort and 3.1% in the unscreened cohort (P = 0.097), hazard ratio (HR) for the unscreened cohort: 1.59 (P = 0.144). Expert revision with contemporary methodology of CIS-negative biopsy samples from patients with metachronous cancer revealed CIS in 17 out of 45 (38%) cases. Decreased risks for metachronous GCC were related to older age at diagnosis (HR 0.52 per 10 years, P < 0.001) and chemotherapy (HR 0.35, P = 0.002). Limitations include the small number of patients in the unscreened cohort and the retrospective study design. Conclusions: Our evaluation of a national population-based screening programme for contralateral CIS in patients with testicular cancer showed no significant difference in the risk for metachronous GCC between a screened and an unscreened cohort. Single-site biopsy including modern immunohistochemistry does not identify all cases of CIS. [ABSTRACT FROM AUTHOR]

We have shown that treatment with bleomycin–etoposide–cisplatin induces a dose-related nephrotoxicity, which during follow-up shows a significant rebound. The nephrotoxicity does not turn into an increased risk of cardiovascular disease or death even though the patients as a whole have a significantly higher number of deaths and cardiovascular events compared with the background population.Background Treatment with bleomycin–etoposide–cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large cohort of germ-cell cancer survivors. Patients and methods BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity. GFR were measured (51Cr-EDTA clearance) before and after treatment and at 1, 3 and 5-year follow-up. The influence of BEP on GFR was evaluated with a linear mixed model. Risk factors for late toxicity were identified by a landmark analysis adjusting for covariates. The cohort was compared with the background population with standardized hospitalization/mortality rates. Results GFR changed (ΔGFR) −11.3%, −15.4% and −25.9% after three, four and five+ cycles of BEP. For patients with impaired renal function before treatment the changes were 4.3%, 0.0% and −12.8%, respectively. During follow-up a significant rebound of GFR was documented. Compared with the background population, all patients, irrespective of renal function, had an increased risk of CVD and death. This risk depended on chronic kidney disease stage before treatment but not after treatment. ΔGFR had no influence on risk of late toxicity [death: hazard ratio (HR) 1.06, P = 0.50; CVD: HR 0.97, P = 0.61]. Conclusions Renal function after BEP is closely related to number of cycles, but the changes in GFR are partly reversible and have no impact on risk of CVD or death. [ABSTRACT FROM PUBLISHER]

This review highlights the considerable clinical extent and importance of muscle dysfunction in cancer patients across all stages and diagnoses. The causes include a range of tumor, therapy- or lifestyle-related factors. Against this background, exercise training may be a potent intervention for maintaining and/or improving muscle mass, strength and metabolism during and after cancer treatment.Background Muscle dysfunction is a prevalent phenomenon in the oncology setting where patients across a wide range of diagnoses are subject to impaired muscle function regardless of tumor stage and nutritional state. Here, we review the current evidence describing the degree, causes and clinical implications of muscle dysfunction in cancer patients. The efficacy of exercise training to prevent and/or mitigate cancer-related muscle dysfunction is also discussed. Design We identified 194 studies examining muscular outcomes in cancer patients by searching PubMed and EMBASE databases. Results Muscle dysfunction is evident across all stages of the cancer trajectory. The causes of cancer-related muscle dysfunction are complex, but may involve a wide range of tumor-, therapy- and/or lifestyle-related factors, depending on the clinical setting of the individual patient. The main importance of muscle dysfunction in cancer patients lies in the correlation to vital clinical end points such as cancer-specific and all-cause mortality, therapy complications and quality of life (QoL). Such associations strongly emphasize the need for effective therapeutic countermeasures to be developed and implemented in oncology practice. Significant progress has been made over the last decade in the field of exercise oncology, indicating that exercise training constitutes a potent modulator of skeletal muscle function in patients with cancer. Conclusion There are clear associations between muscle dysfunction and critical clinical end points. Yet there is a discrepancy between timing of exercise intervention trials, which can improve muscle function, and study populations in whom muscle function are proven prognostic important for clinical end points. Thus, future exercise trials should in early-stage patients, be powered to evaluate clinical outcomes associated with improvements in muscle function, or be promoted in advanced stage settings, aiming to reverse cancer-related muscle dysfunction, and thus potentially improve time-to-progression, treatment toxicity and survival. [ABSTRACT FROM PUBLISHER]

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377–1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478–496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497–513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues.The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements. [ABSTRACT FROM PUBLISHER]

Background: 2-18fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) has been recommended in international guidelines in the evaluation of postchemotherapy seminoma residuals. Our trial was designed to validate these recommendations in a larger group of patients.Patients and methods: FDG-PET studies in patients with metastatic seminoma and residual masses after platinum-containing chemotherapy were correlated with either the histology of the resected lesion(s) or the clinical outcome.Results: One hundred and seventy seven FDG-PET results were contributed. Of 127 eligible PET studies, 69% were true negative, 11% true positive, 6% false negative, and 15% false positive. We compared PET scans carried out before and after a cut-off level of 6 weeks after the end of the last chemotherapy cycle. PET sensitivity, specificity, negative predictive value (NPV), and positive predictive value were 50%, 77%, 91%, and 25%, respectively, before the cut-off and 82%, 90%, 95%, and 69% after the cut-off. PET accuracy significantly improved from 73% before to 88% after the cut-off (P = 0.032).Conclusion: Our study confirms the high specificity, sensitivity, and NPV of FDG-PET for evaluating postchemotherapy seminoma residuals. When carried out at an adequate time point, FDG-PET remains a valuable tool for clinical decision-making in this clinical setting and spares patients unnecessary therapy. [ABSTRACT FROM AUTHOR]

Testicular cancer (TC) is usually diagnosed after manifestation of an overt tumour. Tumour formation is preceded by a pre-invasive and asymptomatic stage, carcinoma in situ (CIS) testis, except for very rare subtypes. The CIS cells are located within seminiferous tubules but can be exfoliated and detected in ejaculates with specific CIS markers. We have built a high throughput framework involving automated immunocytochemical staining, scanning microscopy and in silico image analysis allowing automated detection and grading of CIS-like stained objects in semen samples. In this study, 1175 ejaculates from 765 subfertile men were tested using this framework. In 5/765 (0.65%) cases, CIS-like cells were identified in the ejaculate. Three of these had bilateral testicular biopsies performed and CIS was histologically confirmed in two. In total, 63 bilateral testicular biopsy were performed in conjunction with analysis of the ejaculates because of infertility work-up. Histological analysis of the biopsies for the presence of CIS yielded a test sensitivity of 0.67 and a specificity of 0.98. In addition, ejaculates from 45 patients with clinical signs of an overt TC were investigated and yielded a slightly lower sensitivity (0.51), possibly because of obstruction. We conclude that this novel non-invasive test combining automated immunocytochemistry and advanced image analysis allows identification of TC at the CIS stage with a high specificity, but a negative test does not completely exclude CIS. On the basis of the results, we propose that the assay could be offered to subfertile men and other patients who are at increased risk of TC. [ABSTRACT FROM AUTHOR]

Background: This randomized, phase II study assessed the activity of oblimersen sodium, a Bcl-2 antisense oligonucleotide, administered before docetaxel (Taxotere) to patients with castration-resistant prostate cancer. [ABSTRACT FROM PUBLISHER]

Purpose: Nephrotoxicity and magnesium (Mg)-depletion are well-known side effects to cisplatin (CP) treatment. The purpose of this present study was to investigate the role of Mg on CP induced changes in renal function. CP induced renal dysfunction was achieved by treatment with CP or vehicle (2.5 mg/kg) once weekly for 3 weeks. Since the CP-induced renal damage, including tubular reabsorption defects, is most prominent within the outer medulla (OM), changes in the expression pattern of OM aquaporins and sodium transporters including the Na,K-ATPase (α-subunit), type III Na,H-exchanger (NHE3), aquaporin 1 (AQP1) and 2 (AQP2) and the Na,K,2Cl-cotransporter (NKCC2) were investigated by semi-quantitative Western blotting. Experimental design: Rats had access to either a diet with standard Mg or to a Mg-depleted diet. Cisplatin was administered to female Wistar rats once a week for 3 weeks according to four regimens: (1) Cisplatin 2.5 mg/kg body weight i.p., to rats on a diet with standard Mg, (2) Cisplatin 2.5 mg/kg body weight i.p., to rats on a diet with low Mg, (3) Isotonic NaCl 2.5 ml/kg body weight i.p., to rats on a diet with standard Mg, (4) Isotonic NaCl 2.5 ml/kg body weight i.p., to rats on a diet with low Mg. Results: CP had no effect on plasma creatinine or urea in rats with standard Mg intake, but the expression of all five transporters was significantly reduced when compared to vehicle treated rats on standard Mg-intake. Vehicle treated rats on low Mg-intake had a significant reduction in the expression of Na,K-ATPase, NHE3 and NKCC2, but unchanged expression levels of AQP1 or AQP2 when compared to standard treated controls. Forty percent of the CP-treated rats on low Mg-intake died during the experiment and the remaining animals had marked increased plasma creatinine and urea. Furthermore, the Western blot analysis revealed an almost complete disappearance of all four transporters, suggesting a dramatic synergistic effect of CP and Mg-depletion on renal function including the expression pattern of outer medullary sodium transporters and aquaporins. Conclusions: This study indicates a substantial additive effect of Mg-depletion on cisplatin induced renal toxicity as evidenced by significant changes in plasma creatinine and urea, renal failure induced mortality and loss of renal transporters. This should give cause for concern since the nephrotoxicity observed during cisplatin treatment might be substantiated by the known Mg-loss associated with cisplatin treatment especially in patients suffering from intense gastro-intestinal side effects. [ABSTRACT FROM AUTHOR]

Purpose: Administration of cisplatin causes changes in magnesium and potassium metabolism. The purpose of this study was to investigate day-to-day changes in renal and intestinal homeostasis of magnesium (Mg) and potassium (K) during repeated cisplatin treatments in rats to provide guidelines for human supplementation studies. Experimental design: Rats were housed in metabolic cages with access to a diet containing excess Mg and K. Treatment was administered once a week for 3 weeks and comprised either cisplatin 2.5 mg/kg body weight i.p or, as sham treatment, isotonic NaCl 2.5 ml/kg body weight i.p. Urine and feces were collected every 24 h. Blood samples for measurement of plasma Mg and K were obtained from a permanent arterial catheter prior to each treatment cycle and at the termination of the study. Results: Cisplatin exerted a significant negative effect on total Mg balance. This effect was cumulative with repeated doses of cisplatin. The observed difference was mainly due to the difference in Mg balance between the treatment day and the following 2-3 days. The cumulated urinary excretion of Mg did not differ significantly between the two groups at the end of follow-up. A significant decrease was observed in cumulated intestinal absorption in treated rats compared to control rats at the end of follow-up. Lowered intestinal absorption accounted for 90% of the difference in total Mg balance between the two groups as compared to the renal loss. Cisplatin treatment also exerted a negative effect on total K balance, although the difference between cisplatin-treated and control rats was not significant at the end of follow-up. Conclusions: The Mg loss associated with cisplatin treatment was mainly the result of lowered intestinal absorption and not, as presently thought, the result of increased renal elimination. Instead, an increased renal reabsorption capacity was observed in response to decreased intestinal absorption. The study further showed that Mg and K metabolism are subject to predictable changes in intestinal absorption and renal excretion with each cisplatin treatment, and that knowledge of these changes can be used in planning supplementation. Thus, the experimental observations support intravenous supplementation on the day of treatment and 2-3 days after treatment followed by oral supplementation until the next treatment. [ABSTRACT FROM AUTHOR]