What is the damage? Testicular germ cell tumour survivors deficient in testosterone at risk of metabolic syndrome and a need for medical intervention.

Testicular germ cell tumours (TGCT) survivors are coping with late treatment sequelae. Testosterone deficiency may contribute to earlier onset of metabolic syndrome. The study aimed to assess connections between serum testosterone concentrations and metabolic disorders as well as body composition in TGCT survivors. 336 TGCT patients with over two years of complete post-treatment remission were divided into three groups: definite testosterone deficiency (< 8 nmol/L), 'grey zone' (8-12 nmol/L) and normal testosterone (> 12 nmol/L; control group) to assess differences in metabolism. Univariate and multivariate analyses were performed. The multivariate analysis assessed the risk of metabolic disorders and changes in body composition with regard to testosterone concentrations adjusted for age, smoking history, clinical stage, type of treatment and follow-up period. 14% of patients presented with definite testosterone deficiency; 46% were in the 'grey zone'. On multivariate analysis, low testosterone levels were related to hyperglycemia, hypercholesterolemia, hypertriglyceridemia, inflammatory processes, procoagulant state and obesity. The odds ratio (OR) for the onset of metabolic syndrome was 2.87 (95% CI 1.74-4.73, p < 0.001) for the 'grey zone' patients and 7.92 (95% CI 3.76-16.70, p < 0.001) for those with definite testosterone deficiency. Testosterone concentrations were independently associated with metabolic disorders in TGCT survivors. Testicular cancer survivors often have lower testosterone and metabolic disorders. Apart from recurrence, follow-up should focus on promoting a healthy lifestyle, preventing and managing late effects.

Clinical significance of androgen secretion disorders in men with a malignancy.

Cancer and its treatment can lead in men to testosterone deficiency, accompanied by somatic and mental symptoms. Germ cell tumours and their treatment may disturb the pituitary-gonadal axis, hence leading to significant clinical abnormalities. In some prostate cancer patients, castration, temporary or permanent, is a desired therapeutic condition. Yet, it is burdened with various side effects of complex intensity and significance. Last but not least, patients in the terminal stage of a malignancy present with low testosterone concentrations as a part of anorexia-cachexia syndrome. Oncological management of such patients disturbs their homeostasis, androgen metabolism included, which results in numerous complications and worsens their quality of life. In the present paper, we analysed the frequency and sequelae of testosterone deficiency in some clinical scenarios, on the basis of original papers, meta-analyses and reviews available in PubMed. Androgen secretion disorders in male cancer patients depend on a cancer type, stage and methods of treatment. Number of testicular cancer survivors is increasing, and as a consequence, more patients cope with late complications, testosterone deficiency included. Hormone therapy in prostate cancer patients significantly prolongs survival, and then numerous men experience long-term adverse effects of androgen deficiency. Those, in turn, particularly the metabolic syndrome, may contribute to increased mortality. Androgen deficiency is a part of cancer anorexia-cachexia syndrome. The role of androgen deficiency in cancer patients is still under debate, and further studies are urgently needed to establish appropriate clinical guidelines.

Dynamics of hormonal disorders following unilateral orchiectomy for a testicular tumor.

Testicular tumors and their treatment interfere with homeostasis, hormonal status included. The aim of the study was to evaluate hormonal disorders of the pituitary-gonadal axis in men treated for testicular tumors. One hundred twenty-eight men treated for a unilateral testicular tumor at our institution were included. The hormonal status was prospectively evaluated in 62 patients before orchiectomy, 120 patients 1 month after orchiectomy and 110 patients at least 1 year after the treatment. The concentrations of human chorionic gonadotropin (hCG), testosterone (T), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured. The clinically significant testosterone deficiency was defined either as testosterone <2.31 ng/mL or testosterone within the range of 2.31-3.46 ng/mL but simultaneous with T/LH ratio ≤1. Changes in hormone levels were significant: LH and FSH rose in the course of observation, and the concentration of hCG, testosterone, estradiol decreased. PRL concentration was the lowest at 1 month after orchiectomy. In multivariate analysis, the risk of the clinically significant testosterone deficiency was 0.2107 (95% CI 0.1206-0.3419) prior to orchiectomy, 0.3894 (95% CI 0.2983-0.4889) 1 month after surgery and 0.4972 (95% CI 0.3951-0.5995) 1 year after the treatment. The estradiol concentration was elevated in 40% of patients with recently diagnosed testicular cancer and that was correlated with a higher risk of testosterone deficiency after the treatment completion. Hormonal disorders of the pituitary-gonadal axis in men treated for testicular tumors are frequent. The malignant tissue triggers paraneoplastic disorders that additionally disturb the hormonal equilibrium.

Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered: A Post Hoc Analysis of the Mainsail Study.

IMPORTANCE: The optimal total number of docetaxel cycles in patients with metastatic castration resistant prostate cancer (mCPRC) has not been investigated yet. It is unknown whether it is beneficial for patients to continue treatment upon 6 cycles. OBJECTIVE: To investigate whether the number of docetaxel cycles administered to patients deriving clinical benefit was an independent prognostic factor for overall survival (OS) in a post hoc analysis of the Mainsail trial. DESIGN, SETTING, AND PARTICIPANTS: The Mainsail trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median OS was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group. As the dose intensity was comparable in both treatment arms, we investigated whether the number of docetaxel cycles administered to patients deriving clinical benefit on Mainsail was an independent prognostic factor for OS. We conducted primary univariate and multivariate analyses for the intention-to-treat population. Additional sensitivity analyses were done, excluding patients who stopped treatment for reasons of disease progression and those who received 4 or fewer cycles of docetaxel for other reasons, minimizing the effect of confounding factors. MAIN OUTCOMES AND MEASURES: Total number of docetaxel cycles delivered as an independent factor for OS. RESULTS: Overall, all 1059 patients from the Mainsail trial were included (mean [SD] age, 68.7 [7.89] years). Treatment with 8 or more cycles of docetaxel was associated with superior OS (hazard ratio [HR], 1.909; 95% CI, 1.660-2.194; P < .001), irrespective of lenalidomide treatment (HR, 1.060; 95% CI, 0.924-1.215; P = .41). Likewise, in the sensitivity analysis, patients who received a greater number of docetaxel cycles had superior OS; patients who received more than 10 cycles had a median OS of 33.0 months compared with 26.9 months in patients treated with 8 to 10 cycles; and patients who received 5 to 7 cycles had a median OS of 22.8 months (P < .001). CONCLUSIONS AND RELEVANCE: These findings suggest that continuation of docetaxel chemotherapy contributes to the survival benefit. Prospective validation is warranted.

Circulating Tumor Cells in a Phase 3 Study of Docetaxel and Prednisone with or without Lenalidomide in Metastatic Castration-resistant Prostate Cancer.

Elevated circulating tumor cell (CTC) blood levels (≥5 cells/7.5ml) convey a negative prognosis in metastatic castration-resistant prostate cancer but their prognostic significance in patients receiving chemotherapy is uncertain. The association between CTC counts (at baseline or after treatment), overall survival (OS), and response to docetaxel with lenalidomide was evaluated in a 208-patient subset from the MAINSAIL trial, which compared docetaxel-prednisone-lenalidomide and docetaxel-prednisone-placebo in metastatic castration-resistant prostate cancer patients. Baseline CTCs were <5 cells/7.5ml blood in 87 (42%) patients and ≥5 cells/7.5ml in 121 (58%) patients. Neither tumor response nor prostate-specific antigen response correlated with baseline CTCs. However, CTC count ≥5 cells/7.5ml was significantly associated with lower OS (hazard ratio: 3.23, p = 0.0028). Increases in CTCs from <5 cells/7.5ml to ≥5 cells/7.5ml after three cycles were associated with significantly shorter OS (hazard ratio: 5.24, p=0.025), whereas CTC reductions from ≥5 cells/7.5ml to <5 cells/7.5ml were associated with the best prognosis (p=0.003). PATIENT SUMMARY: Our study in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy, with or without lenalidomide, showed that patient survival was best predicted by circulating tumor cell count at the start of treatment. A rising circulating tumor cell count after three cycles of therapy predicted poor survival, while a decline predicted good survival.

Does pharmacological castration as adjuvant therapy for prostate cancer after radiotherapy affect anxiety and depression levels, cognitive functions and quality of life?

INTRODUCTION: Adjuvant hormonotherapy for prostate cancer patients after radical radiotherapy has a well-established value. However, the impact of such treatment on the patients' quality of life remains to be elucidated. OBJECTIVE: The objective is to assess the impact of adjuvant hormonotherapy with luteinizing hormone-releasing hormone analogue after radical radiotherapy on anxiety and depression levels, cognitive function, sexual function and quality of life of prostate cancer patients. MATERIAL AND METHODS: Two groups of patients were tested: men treated with adjuvant hormonotherapy (88 patients) and men without hormonotherapy (61 patients). Anxiety, depression and cognitive functions were evaluated. Patients answered questions addressing problems linked to hormonal equilibrium. The patients rated their mental status, physical status, quality of life and quality of their relationship. RESULTS: There were no statistically significant differences between patients on hormonotherapy and without hormonotherapy in the level of anxiety and depression (p = 0.844 and p = 0.954) as well as in cognitive function (p = 0.661). Satisfactory sexual performance was preserved in 9/65 patients (14%) on hormonotherapy and the same was applied to 19/49 patients (39%) without hormonotherapy. The difference was statistically significant (p = 0.003). Hormonotherapy was associated with decreased libido (p = 0.031), hot flushes (p < 0.001) and sweating (p < 0.001). No statistically significant differences were found between the groups in the self-rated physical and psychological well-being (p = 0.476 and p = 0.597), quality of life (p = 0.622) and quality of relationship (p = 0.064). CONCLUSIONS: Adjuvant hormonotherapy enhances neither anxiety nor depression, does not impair cognitive function but has a negative effect on the patients' sexual function. It does not worsen self-rated quality of relationship and quality of life.