Re-establishing the Role of Robot-assisted Radical Cystectomy After the 2020 EAU Muscle-invasive and Metastatic Bladder Cancer Guideline Panel Recommendations.

The EAU guidelines panel on muscle-invasive and metastatic bladder cancer (MIBC) recently recommended open radical cystectomy (ORC) as the best surgical approach for MIBC patients. We critically re-examine the indications for considering ORC as the first choice over robot-assisted radical cystectomy. To the best of our knowledge, this is not supported by trials or meta-analyses.

Do Learning Disabilities Affect Testicular Cancer Survival: A National Cohort Study Between 2001 and 2015.

BACKGROUND: Some 1.5 million people in the UK have a learning disability (LD). This vulnerable group derives less benefit from population-based education programs. They are prone to underenrolment in screening programs and may lack the ability to perform self-examination. OBJECTIVE: To identify patients with LD in England and assess their testicular cancer (TC) survival in comparison to the general population. DESIGN, SETTING, AND PARTICIPANTS: Patient records were identified from the Hospital Episode Statistics database. All patients resident in England with a diagnosis of mental debility, "developmental disorder of scholastic skills", or attending under the specialty of LD between April 1, 2001 and June 30, 2015 were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured survival outcomes according to the Kaplan-Meier method and used log-rank tests to assess survival difference between demographic groups. RESULTS AND LIMITATIONS: Of 158138 male patients with LD, 331 had TC and 32 died of cancer. LD patients had a poorer prognosis, with 10-yr TC-specific survival of 88.4% (95% confidence interval [CI] 84.5-92.4%) in the LD group versus 96.8% (95% CI 96.6-97.1%) in the non-LD group. LD patients also had lower all-cause survival rates. The 10-yr survival rate was 77.6% (95% CI 72.2-83.3%) for LD patients versus 89.9% (95% CI 89.4-90.3%) for non-LD patients, while the corresponding 5-yr rates were 84% (95% CI 79.9-88.4%) versus 92.2% (95% CI 91.8-92.5%). CONCLUSIONS: Education regarding self-examination for TC must be provided in a format suitable for those with LD. Carers for male patients with LD should be informed about testicular examination and sinister signs. PATIENT SUMMARY: Testicular cancer patients who also have a learning disability (LD) have a one in nine chance of dying, compared to a one in 36 chance for testicular cancer patients without LD. This is because patients with LD are less likely to detect the disease at an earlier stage.

Chronic tyrosine kinase inhibitor (TKI) use in metastatic renal cell carcinoma (mRCC): can this lead to the adverse effect of hypogonadism?

Background: Patients with metastatic renal cell carcinoma (mRCC) are commonly treated with tyrosine kinase inhibitors (TKIs). An adverse effect frequently suffered by patients is lethargy, which often leads to dose reduction or drug cessation. We aimed to assess whether hypogonadism is related to treatment with TKIs. Methods: We prospectively assessed gonadal function in 41 consecutive males with mRCC treated with TKIs. Demographic, clinical, and biochemical variables were collected, and statistical analyses performed to assess correlation and survival. Data Capture for each patient was perfomred at the time of entry in the study. Results: There was a 77% incidence of hypogonadism in this cohort. Assessment of testosterone level and time on TKI treatment revealed a correlation with linear regression R2 of 0.24 and regression coefficient of -0.003 (p = 0.019). Odds ratio for hypogonadism at >30 months on TKIs was 12.1 (p = 0.011). Odds ratios above and below this value showed a confirmatory trend, suggesting that this may be a chronic adverse effect. Conclusions: Our findings provide an important and robust hypothesis for a prospective clinical trial to be performed. Expert Opinion: Given the present data, patients who have symptoms suggestive of hypogonadism must have an assessment of gonadal function and be treated.

High miR-205 expression in normal epithelium is associated with biochemical failure - an argument for epithelial crosstalk in prostate cancer?

Due to insufficient prognostic tools, failure to predict aggressive prostate cancer (PC) has left patient selection for radical treatment an unsolved challenge. This has resulted in overtreatment with radical therapy. Better prognostic tools are urgently warranted. MicroRNAs (miRs) have emerged as important regulators of cellular pathways, resulting in altered gene expressions. miR-205 has previously been observed downregulated in PC, acting as tumor suppressor. Herein, the expression of miR-205 in prostate tissue was examined in a large, well-described cohort of 535 Norwegian prostatectomy patients. Using in situ hybridization, miR-205 expression was semiquantatively measured in normal and tumor tissues from radical prostatectomy specimens. Associations with clinicopathological data and PC relapse were calculated. Expression of miR-205 was lower in tumor epithelium compared to normal epithelium. No association was observed between miR-205 expression in primary tumor epithelium and cancer relapse. In contrast, high expression of miR-205 in normal epithelium was independently associated with biochemical relapse (HR = 1.64, p = 0.003). A prognostic importance of miR-205 expression was only found in the normal epithelium, raising the hypothesis of epithelial crosstalk between normal and tumor epithelium in PC. This finding supports the proposed novel hypothesis of an anti-cancerogenous function of normal epithelium in tumor tissue.

High expression of PDGFR-ß in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence.

Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the prognostic impact of PDGFR-ß and its ligands (PDGF-B and PDGF-D) in a multicenter prostatectomy cohort of 535 Norwegian patients. Using tissue microarrays and immunohistochemistry, the expression of ligands PDGF-B and PDGF-D and their corresponding receptor, PDGFR-ß, was assessed in neoplastic tissue and tumor-associated stroma. PDGFR-ß was expressed in benign and tumor associated stroma, but not in epithelium. High stromal expression of PDGFR-ß was independently associated with clinical relapse (HR = 2.17, p = 0.010) and biochemical failure (HR = 1.58, p = 0.002). This large study highlights the prognostic importance of PDGFR-ß expression, implicating its involvement in prostate cancer progression even in early stage disease. Hence, analyses of PDGFR-ß may help distinguish which patients will benefit from radical treatment, and since PDGFR-ß is associated with relapse and shorter survival, it mandates a focus as a therapeutic target.

Stromal expression of VEGF-A and VEGFR-2 in prostate tissue is associated with biochemical and clinical recurrence after radical prostatectomy.

BACKGROUND: There is probably significant overtreatment of patients with prostate cancer due to a lack of sufficient diagnostic tools to predict aggressive disease. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are potent mediators of angiogenesis and tumor proliferation, but have been examined to a limited extent in large prostate cancer studies. Meanwhile, recent promising results on VEGFR-2 inhibition have highlighted their importance, leading to the need for further investigations regarding their expression and prognostic impact. DESIGN: Using tissue microarray and immunohistochemistry, the expression of VEGFs (VEGF-A and VEGF-C) and their receptors (VEGFR-2 and VEGFR-3) were measured in neoplastic tissue and corresponding stroma from radical prostatectomy specimens in 535 Norwegian patients. Their expression was evaluated semiquantatively and associations with event-free survival were calculated. RESULTS: High expression of VEGFR-2 in either stroma or epithelium was independently associated with a higher incidence of prostate cancer relapse (HR = 4.56, P = 0.038). A high combined expression of either VEGF-A, VEGFR-2 or both in stroma was independently associated with a higher incidence of biochemical failure (HR = 1.77, P = 0.011). CONCLUSIONS: This large study highlights the prognostic importance of VEGF-A and VEGFR-2 stromal expression. Analyses of these biomarkers may help distinguish which patients will benefit from radical treatment. Together with previous studies showing efficiency of targeting VEGFR-2 in prostate cancer, this study highlights its potential as a target for therapy, and may aid in future selection of prostate cancer patients for novel anti-angiogenic treatment.

Prostate cancer. Foreword.

Professor Hiten Patel is an expert in Laparoscopic and Robotic Surgery for treating prostate disease. He is also a leading researcher in basic science and `clinical research. His basic science research is focused on studying the pathways for improving prostate cancer diagnosis and prognosis through biomarker application, and his clinical research includes new technology applications for training surgeons and improving patient care outcome. Prof Patel is also Chairman of the Urology group for the Enhanced Recovery after Surgery Society.

Robotic and minimal access surgery: technology and surgical outcomes of radical prostatectomy for prostate cancer.

Since the 1990s, minimal access surgery has been utilized in urology. In the past 15 years, robotic surgery has evolved and become a natural part of minimal access surgery. The dissemination has been fast and the opportunity of prospective trials has been missed. Nevertheless, robotic surgery has obvious benefits for the surgeon and patient. Even though the scientific evidence is not strong, robotic surgery is here to stay. However, there are lessons to learn from the implementation of the da Vinci system with regards to patient safety and prospective evaluation of the new technology. The future of surgery will include technologies derived from robotic surgery.

Biomarkers and personalized risk stratification for patients with clinically localized prostate cancer.

Prostate cancer (PCa) is the most common neoplasia among men in developed countries and a leading cause of cancer-related morbidity and mortality. PCa is a very heterogeneous disease, both clinically and biologically. Currently, it is difficult to stratify patients into risk groups that entail different disease management. Therefore, a personalized view of this disease is mandatory, through the development of new and more accurate biomarkers that may help clinicians to stratify patients according to threat that PCa poses for each patient. Hence, this review focuses on recent developments of molecular and immunohistochemical biomarkers for PCa risk stratification that might enable a personalized approach to PCa patients. However, despite the increasing amount of available data, there is also an urgent need to translate the most promising biomarkers for clinical use through large multicenter validation trials. Ultimately, these will contribute for an improved clinical management of PCa patients.

Strategies to improve quality of life in bladder cancer patients.

Bladder cancer is a heterogeneous disease that includes both tumors with low risk of dissemination as well as highly malignant tumors with a considerable potential to metastasize. The patient's quality of life is closely related to the management of the disease. The challenge for the urologist is to acknowledge the malignant potential of the cancer and to adjust the approach to the patient accordingly. Patients with low-risk bladder cancer should avoid an exaggerated follow-up, but on the other hand high-risk patients must be sufficiently surveyed to secure that definitive surgical treatment is performed before it's too late. When the decision to perform a cystectomy has been made, it is crucial that the patient understands the consequences of the surgery as well as the possible options for urinary reconstruction. This review focuses on aspects of bladder cancer management that we believe are vital for the quality of life of these patients.

Predicting erectile function outcome in men after radical prostatectomy for prostate cancer.

OBJECTIVE: • To identify the reported rates of potency after prostatectomy in the recent literature for men without preoperative erectile dysfunction (ED) and to develop a statistical model for predicting the expected potency after prostatectomy. MATERIALS AND METHODS: • A Medline search was conducted with the keywords 'potency' and 'prostatectomy' from 2003 to 2009. • In total, 33 studies in the English language reporting pre- and postoperative erectile function were identified. • Data from studies reporting outcome after open, laparoscopic and robot-assisted prostatectomy were analyzed separately. • Only data obtained from potent men before surgery were included in the analysis. RESULTS: • In potent men before surgery, the main predictors of post-treatment erectile function are age and time after treatment. • The cumulative range of potency rates at 48 months for all ages (45-75 years) was 49-74% for open, 58-74% for laparoscopic and 60-100% for robotic prostatectomy. • The predicted outcome differs by type of operation and patient age. CONCLUSIONS: • Men aged <60 years have a significant likelihood of regaining erectile function after radical prostatectomy. • The reported statistical model provides a reliable estimation of erectile function outcome after prostatectomy for men with localized prostate cancer and intact erectile function.

Robotic and laparoscopic surgery: cost and training.

Robotic prostatectomy training as part of mainstream surgical training will be difficult. The primary problems revolve around the inconsistencies of standard sugery. Many surgeons are still in the learning curve, as is the understanding of the true capabilities of the robot. The important elements of robotic surgery actually enhance basic laparoscopic techniques. The prostate has been shown to be an organ where this new technology has a niche. As we move toward cross specialty use the robot although extremely expensive, may be the best way to train the laparoscopic surgeon of the future.

Salvage laparoscopic surgery in advanced prostate cancer: is it possible or beneficial?

PURPOSE: The surgical management of recurrent urological cancer continues to evolve. This review focuses on the role laparoscopic surgical techniques have within recurrent prostate treatments. METHODS: A literature search from 1990 to 2007 was conducted using the PubMed database to determine the role of laparoscopic salvage surgery for prostate cancers. In all articles studied, we evaluated: estimated blood loss; transfusion rates; hemoglobin level; serum and drain fluid creatinine levels; bowel injury; hospital stay and complication rates. RESULTS: Laparoscopic surgery is used regularly for the treatment of urological cancers; however, its role in treating radiorecurrent or chemoradiorecurrent cancer is unknown. Adjuvant chemo-radiotherapy, other experimental localized therapies (cryotherapy) or hormonal therapy are known to affect the operative field, causing greater morbidity in open surgery. Relative survival rates were lowest among patients who received no treatment and highest among patients who underwent surgical procedures. CONCLUSIONS: Although associated with significant morbidity, salvage prostatectomy remains a viable form of therapy. Laparoscopic salvage radical prostatectomy for recurrent cancer is feasible with no more morbidity than an open procedure, with promising short-term oncologic and functional outcomes. Long-term data will ultimately confirm the viability of the laparoscopic approach most probably in a multicenter setting.

Significance of alterations in plasma lipid profile levels in breast cancer.

HYPOTHESES: The relationship between lipids and breast cancer is obscure. Until now, conflicting results have been reported on the association between lipids and risk of breast cancer in women. Therefore, the major aim of this study is to examine the role of alterations in lipid profile in breast cancer. STUDY DESIGN: Plasma lipids (ie, total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very-low-density lipoprotein [VLDL], and triglycerides [TG]) were analyzed from 70 controls, 30 patients with benign breast disease (BBD), 125 untreated breast cancer patients, and 93 posttreatment follow-up samples. METHODS: Samples were analyzed using highly sensitive and specific spectrophotometric methods. RESULTS: Plasma TC, LDL, VLDL, and TG were significantly lower (p = .042, p = .003, p = .024, p = .014, respectively) in patients with BBD compared with controls. Plasma TC and HDL were significantly lower (p = .026, p = .0001, respectively), and VLDL and TG were significantly higher (p = .009, p = .05) in breast cancer patients as compared with controls. Plasma VLDL and TG were significantly higher in breast cancer patients as compared with patients with BBD. The receiver-operating characteristic curve showed that plasma TC, LDL, VLDL, and TG levels could significantly discriminate (p = .001, p = .005, p = .005, p = .005, respectively) between controls and patients with BBD. Plasma levels of TC, HDL, VLDL, and TG could significantly distinguish (p = .01, p = .002, p = .001, p = .002, respectively) between controls and breast cancer patients. Plasma levels of VLDL and TG could significantly discriminate (p = .000, p = .000, respectively) between patients with BBD and breast cancer patients. Odds ratio analysis revealed that higher levels of TC and HDL were significantly associated with a reduction in breast cancer risk (p = .01 and p = .0001, respectively), whereas higher levels of VLDL and TG were significantly associated with increased breast cancer risk (p = .001 and p = .002, respectively). Plasma VLDL and TG levels were significantly lower in complete responders as compared with pretreatment levels (p = .000, p = .000, respectively), and plasma TC and LDL levels were significantly lower in nonresponders as compared with pretreatment levels (p = .015, p = .009, respectively). CONCLUSION: The alterations in lipid profile levels showed a significant correlation with breast cancer risk, disease status, and treatment outcome.