Time pressure predicts decisional regret in men with localized prostate cancer: data from a longitudinal multicenter study

Purpose: A substantial proportion of men with localized prostate cancer (lPCa) later regret their treatment decision. We aimed to identify factors contributing to decisional regret. Methods: We conducted a longitudinal study, in which men with lPCa were surveyed at four measurement points: T0 (baseline) = prior to treatment; T1 = 6; T2 = 12; T3 = 18 months after baseline. chi(2)-tests and independent t-tests were used to compare men undergoing different treatments [Active Surveillance (AS) vs. local treatment]. Logistic regression models were fitted to investigate the associations between predictors (time pressure, information provided by the urologist, impairment of erectile functioning, satisfaction with sexual life) and the criterion decisional regret. Results: At baseline, the sample included N = 176 men (AS: n = 100; local treatment: n = 76). At T2 and T3, men after local therapies reported higher regret than men under AS. Decisional regret at T3 was predicted by time pressure at baseline (OR 2.28; CI 1.04-4.99; p < 0.05), erectile dysfunction at T2 and T3 (OR 3.40; CI 1.56-7.42; p < 0.01), and satisfaction with sexual life at T1-T3 (OR 0.44; CI 0.20-0.96; p < 0.05). Conclusions: Time pressure, erectile dysfunction, and satisfaction with sexual life predict decisional regret in men with lPCa. Mitigating time pressure and realistic expectations concerning treatment side effects may help to prevent decisional regret in PCa survivors

Small renal carcinoma : the "when" and "how" of operation, active surveillance, and ablation

Small, locally restricted renal cell carcinoma less than 4 cm in size should ideally be removed operatively by nephron-sparing tumour enucleation (partial kidney resection). In an increasingly elderly population, there is a growing trend toward parallel incidence of renal cell carcinoma and chronic renal insufficiency, with the latter's associated general comorbidities. Thus, for some patients, the risks of the anaesthesia and operation increase, while the advantage in terms of survival decreases. Transcutaneous radio-frequency ablation under local anaesthesia, transcutaneous afterloading high-dose-rate brachytherapy under local anaesthesia, and percutaneous stereotactic ablative radiotherapy may offer a less invasive alternative therapy. Active surveillance is to be regarded as no more than a controlled bridging up to definitive treatment (operation or ablation), while watchful waiting, on account of the lack of prognostic relevance and the symptomatology of renal cell carcinoma, with its comorbidity-related, clearly reduced life expectancy, does not involve any further diagnostic or therapeutic measures

Morbidity and Quality of Life in Bladder Cancer Patients following Cystectomy and Urinary Diversion: A Single-Institution Comparison of Ileal Conduit versus Orthotopic Neobladder

Objective. To evaluate and compare noncontinent and continent urinary diversion after radical cystectomy in patients with bladder cancer. Methods. A total of 301 patients submitted to radical cystectomy at the Charité-University Hospital Berlin from 1993 to 2007 including 146 with an ileal conduit and 115 with an ileal neobladder. Clinical and pathological data as well as oncological outcome were retrospectively analyzed and compared. Quality of life was analyzed using the EORTC QLQ-C30 and BLM30 questionnaires. Results. 69.1% and 69.6% of all patients who received an ileal conduit and ileal neobladder, respectively, developed early complications. The two groups differed significantly concerning the occurrence of postoperative ileus (P = 0.02) favoring patients who received an ileal conduit but not with regard to any other early-onset complication evaluated. Patients with ileal neobladder had a significantly better global health status and quality of life (P = 0.02), better physical functioning (P = 0.02), but also a higher rate of diarrhoea (P = 0.004). Conclusion. Cystectomy with any type of diversion remains a complication-prone surgery. Even if the patient groups are not homogeneous in all respects, there are many arguments in favor of the ileal neobladder as the urinary diversion of choice

Inability of shear-wave elastography to distinguish malignant from benign prostate tissue – a comparison of biopsy, whole-mount sectioning and shear-wave elastography

Aim: This study was designed to assess the possible usefulness of shear-wave elastography in differentiating between benign and malignant tissue in prostate neoplasia. Patients and methods: A total of 120 prostate tissue samples were obtained from 10 patients treated by radical prostatectomy and investigated pre-operatively by ultrasound elastography followed by directed biopsy. After resection, whole-mount sectioning and histological examination was performed. The predictions based on shear-wave elastography were compared with biopsy and histological results. Results: The comparison between the results of shear-wave elastography and those of biopsy was performed by receiver operating characteristic analysis, which suggested an optimum cut-off tissue elasticity value of 50 kPa, in agreement with earlier studies aimed at distinguishing between benign and malignant tissue. However, the diagnostic selectivity (and thus the diagnostic power) was poor (area under the curve 0.527, which hardly differs from the value of 0.500 that would correspond to a complete lack of predictive power); furthermore, application of this cut-off value to the samples led to a sensitivity of only 74% and a specificity of only 43%. An analogous comparison between the results of shear-wave elastography and those of whole-mount histology, which itself is more reliable than biopsy, gave an even poorer diagnostic selectivity (sensitivity of 62%, specificity of 35%). Meaningful association with Gleason score was not found for D'Amico risk groups (p = 0.35). Conclusions: The (negative) findings of this investigation add to the dissonance among results of studies investigating the possible value of shear-wave elastography as a diagnostic tool to identify malignant neoplasia. There is a clear need for further research to elucidate the diversity of study results and to identify the usefulness, if any, of the method in question

Impact of hormonal therapy on the detection of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) in prostate cancer

BACKGROUND: In spite of excellent cure rates for prostate cancer patients with favorable tumor characteristics, patients with unfavorable characteristics after radical prostatectomy are still at a significantly increased risk of tumor progression. Early adjuvant hormonal therapy (AHT) has been shown to be of prognostic benefit in these patients. Unfortunately initiation and duration of early AHT in the individual patient is based on statistic data. PSA, as the standard prostate marker is neither able to reliably indicate minimal residual tumor disease in the early postoperative phase, nor can it be used for therapy monitoring due to the suppressive effect of hormonal therapy on PSA production. Promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1-HM) has been shown to be the most common DNA alteration of primary prostatic carcinoma which, when used as a marker, is supposed to be able to overcome some of the disadvantages of PSA. However until now information on the impact of hormonal therapy on the detection of GSTP1-HM is lacking. The purpose of our study was to assess the impact of endocrine therapy on the detection of GSTP1-HM by methylation-specific PCR (MSP) in prostate cancer. METHODS: Paraffin embedded tumor samples from the radical prostatectomy (RP) specimens from 15 patients after hormonal therapy (HT) (mean 8 months) were assessed by MSP. In 8 of the patients the GSTP-1 status of the tumors before HT was assessed on the corresponding initial diagnostic biopsies. RESULTS: Following HT MSP showed GSTP1-HM in 13/15 of the RP specimens. In two patients analysis of the RP specimens failed to show GSTP1-HM. All initial tumor samples (8/8 biopsy specimens) showed GSTP1-HM, including both patients negative for GSTP1 HM in the corresponding RP specimen. CONCLUSION: In most cases hormonal therapy appears to not alter GSTP1 HM detection. However the change from a positive to a negative GSTP1 HM status in a subset of the patients may point to an, at least partial androgen dependency. Further studies on a larger cohort of patients are necessary to assess its frequency and the exact hormonal interactions

Awareness and perception of multidrug-resistant organisms and antimicrobial therapy among internists vs. surgeons of different specialties: Results from the German MR2 Survey

Background: Recently, antibiotic resistance rates have risen substantially and care for patients infected with multidrug-resistant organisms (MDRO) has become a common problem in most in &#8211; and outpatient settings. The objectives of the study were to compare the awareness, perception, and knowledge of MDRO and rational antibiotic use between physicians from different medical specialties in German hospitals. Methods: A 35-item questionnaire was sent to specialists in internal medicine (internists), gynecologists, urologists, and general surgeons (non-internists) in 18 German hospitals. Likert-scales were used to evaluate awareness and perception of personal performance regarding care for patients infected with MDRO and rational use of antibiotics. Additionally, two items assessing specific knowledge in antibiotic therapy were included. The impact of medical specialty on four predetermined endpoints was assessed by multivariate logistic regression. Results: 43.0 (456/1061) of recipients responded. Both internists and non-internists had low rates of training in antibiotic stewardship. 50.8 of internists and 58.6 of non-internists had attended special training in rational antibiotic use or care for patients infected with MDRO in the 12 months prior to the study. Internists deemed themselves more confidently to choose the indications for screening patients for colonization with methicillin-resistant Staphylococcus aureus (P=0.004) and to initiate adequate infection control measures (P=0.002) than other specialties. However, there was no significant difference between internists and other specialists regarding the two items assessing specific knowledge in antibiotic therapy and infection control. Conclusion: Among the study participants, a considerable need for advanced training in the study subjects was seen, regardless of the medical specialty

Does the Identification of a Minimum Number of Cases Correlate With Better Adherence to International Guidelines Regarding the Treatment of Penile Cancer? Survey Results of the European PROspective Penile Cancer Study (E-PROPS)

Background: Penile cancer represents a rare malignant disease, whereby a small caseload is associated with the risk of inadequate treatment expertise. Thus, we hypothesized that strict guideline adherence might be considered a potential surrogate for treatment quality. This study investigated the influence of the annual hospital caseload on guideline adherence regarding treatment recommendations for penile cancer. Methods: In a 2018 survey study, 681 urologists from 45 hospitals in four European countries were queried about six hypothetical case scenarios (CS): local treatment of the primary tumor pTis (CS1) and pT1b (CS2); lymph node surgery inguinal (CS3) and pelvic (CS4); and chemotherapy neoadjuvant (CS5) and adjuvant (CS6). Only the responses from 206 head and senior physicians, as decision makers, were evaluated. The answers were assessed based on the applicable European Association of Urology (EAU) guidelines regarding their correctness. The real hospital caseload was analyzed based on multivariate logistic regression models regarding its effect on guideline adherence. Results: The median annual hospital caseload was 6 (interquartile range (IQR) 3–9). Recommendations for CS1–6 were correct in 79%, 66%, 39%, 27%, 28%, and 28%, respectively. The probability of a guideline-adherent recommendation increased with each patient treated per year in a clinic for CS1, CS2, CS3, and CS6 by 16%, 7.8%, 7.2%, and 9.5%, respectively (each p < 0.05); CS4 and CS5 were not influenced by caseload. A caseload threshold with a higher guideline adherence for all endpoints could not be perceived. The type of hospital care (academic vs. non-academic) did not affect guideline adherence in any scenario. Conclusions: Guideline adherence for most treatment recommendations increases with growing annual penile cancer caseload. Thus, the results of our study call for a stronger centralization of diagnosis and treatment strategies regarding penile cancer

Efficacy and Safety of Darolutamide in Patients with Nonmetastatic Castration-resistant Prostate Cancer Stratified by Prostate-specific Antigen Doubling Time : Planned Subgroup Analysis of the Phase 3 ARAMIS Trial

Background: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo. However, patients remain at a high risk with a PSADT of >6 mo. Objective: To evaluate the efficacy and safety of darolutamide versus placebo in patients stratified by PSADT >6 or ≤6 mo. Design, setting, and participants: A planned subgroup analysis of a global multicenter, double-blind, randomized, phase 3 trial in men with nmCRPC and PSADT ≤10 mo was conducted. Intervention: Patients were randomized 2:1 to oral darolutamide 600 mg twice daily or placebo, while continuing androgen-deprivation therapy. Outcome measurements and statistical analysis: The primary endpoint was metastasis-free survival (MFS). Secondary endpoints were overall survival (OS) and times to pain progression, first cytotoxic chemotherapy, and symptomatic skeletal events. Quality of life (QoL) was measured using validated prostate-relevant tools. Safety was recorded throughout the study. Results and limitations: Of 1509 patients enrolled, 469 had PSADT >6 mo (darolutamide n = 286; placebo n = 183) and 1040 had PSADT ≤6 mo (darolutamide n = 669; placebo n = 371). Baseline characteristics were balanced between subgroups. Darolutamide significantly prolonged MFS versus placebo in both subgroups (unstratified hazard ratio [95% confidence interval]: PSADT >6 mo, 0.38 [0.26–0.55]; PSADT ≤6 mo, 0.41 [0.33–0.52]). OS and other efficacy and QoL endpoints favored darolutamide with significant improvement over placebo in both subgroups. The incidence of adverse events, including events commonly associated with androgen receptor inhibitors (fractures, falls, hypertension, and mental impairment), and discontinuations due to adverse events were low and similar to placebo. Limitations include small subgroup populations. Conclusions: In patients with nmCRPC and PSADT >6 mo (maximum 10 mo), darolutamide provided a favorable benefit/risk ratio, characterized by significant improvements in MFS, OS, and other clinically relevant endpoints; maintenance of QoL; and favorable tolerability. Patient summary: In patients with prostate cancer that has stopped responding to standard hormonal therapy (indicated by an increase in prostate-specific antigen [PSA] levels), there is a risk that the cancer will spread to other parts of the body. This risk is highest when the time it takes for the PSA level to double (ie, “PSA doubling time” [PSADT]) is less than 6 mo. However, there is still a risk that the cancer will spread even if the PSADT is longer than 6 mo. In a group of patients whose PSADT was more than 6 mo but no more than 10 mo, treatment with darolutamide slowed the cancer spread and allowed them to live longer than patients who received placebo (inactive drug). Darolutamide treatment did not cause many side effects and helped maintain patients’ quality of life without disruptions.publishedVersionPeer reviewe

The differentiation status of primary gonadal germ cell tumors correlates inversely with telomerase activity and the expression level of the gene encoding the catalytic subunit of telomerase

BACKGROUND: The activity of the ribonucleoprotein enzyme telomerase is detectable in germ, stem and tumor cells. One major component of telomerase is human telomerase reverse transcriptase (hTERT), which encodes the catalytic subunit of telomerase. Here we investigate the correlation of telomerase activity and hTERT gene expression and the differentiation status of primary testicular germ cell tumors (TGCT). METHODS: Telomerase activity (TA) was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by online RT-PCR in 42 primary testicular germ cell tumors. The control group consisted of benign testicular biopsies from infertile patients. RESULTS: High levels of telomerase activity and hTERT expression were detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content. In contrast, differentiated teratomas and testicular control tissue without germ cells (Sertoli-cell-only syndrome) showed no telomerase activity and only minimal hTERT expression. CONCLUSIONS: These findings demonstrate an inverse relationship between the level of telomerase activity and hTERT mRNA expression and the differentiation state of germ cell tumors. Quantification of telomerase activity and hTERT mRNA expression enables a new molecular-diagnostic subclassification of germ cell tumors that describes their proliferation potential and differentiation status