Developing an effective strategy to improve the detection of significant prostate cancer by combining the 4Kscore and multiparametric MRI.

OBJECTIVES: Recent years have seen the development of biomarkers and imaging technologies designed to improve the specificity of PSA. Widespread implementation of imaging technologies, such as mp-MRI raises considerable logistical challenges. Our objective was to evaluate a biopsy strategy that utilizes selective mp-MRI as a follow-up test to biomarkers to improve the detection of significant prostate cancer. METHODS AND MATERIALS: We developed a conceptual approach based on the risk calculated from the 4Kscore using results from the US prospective validation study, multiplied by the likelihood ratio of mp-MRI from the PROMIS trial. The primary outcome was Gleason grade ≥ 7 (grade group ≥ 2) cancer on biopsy. Using decision curve analysis, the net benefit was determined for our model and compared with the use of the 4Kscore and mp-MRI independently at various thresholds for biopsy. RESULTS: For a cut-point of 7.5% risk of high-grade disease, patients with <5% risk from a blood marker would not have risk of significant prostate cancer sufficiently increased by a positive mp-MRI to warrant biopsy; comparably, patients with a risk >23% would not have risk sufficiently reduced by a negative imaging study to forgo biopsy. From the 4Kscore validation study, 46% of men considered for biopsy in the US have risks 5% to 23%. Net benefit was highest for the combined strategy, followed by 4Kscore alone. CONCLUSIONS: Selective mp-MRI in men with intermediate scores on a secondary blood test results in a biopsy strategy that is more scalable than mp-MRI for all men with elevated PSA. Prospective validation is required to demonstrate if the predicted properties of combined blood and imaging testing are empirically confirmed.

New Imaging Techniques in Prostate Cancer.

Rapid advances in diagnostic imaging have been developed in parallel with the changes in the contemporary management of prostate cancer. Increasingly, clinical management and decision making in prostate cancer are influenced by technologies such as magnetic resonance imaging-targeted prostate biopsies for men with elevated PSA, imaging for active surveillance, and nuclear medicine studies for men with advanced or recurrent prostate cancer. Furthermore, novel imaging techniques have been developed such as hyperpolarized MRI, choline and prostate-specific membrane antigen positron emission tomography that exploit features like the unique metabolism in prostate cancer tissues, as well as altered glycoprotein conformation. These technologies have allowed for the identification of tiny foci of prostate cancer in men with early biochemical recurrence, greatly surpassing the limitations of traditional morphological imaging. With promising findings, studies are ongoing to uncover the clinical application of these imaging modalities. Ultimately, several factors such as cost-effectiveness and the overall reduction in disease mortality will dictate the implementation of these imaging technologies in the future. This chapter provides an overview on new and emerging prostate imaging techniques that can be used in the diagnosis of primary cancer as well as the staging and detection of metastatic disease.

Long-Term Cancer Specific Anxiety in Men Undergoing Active Surveillance of Prostate Cancer: Findings from a Large Prospective Cohort.

PURPOSE: Active surveillance is the preferred management of low risk prostate cancer. Cancer specific anxiety during active surveillance remains under studied. We evaluated long-term anxiety in men on active surveillance to determine whether interventions must be tailored to improve adherence. MATERIALS AND METHODS: A total of 413 men enrolled in active surveillance at a single tertiary care center completed quality of life surveys as part of routine care. A modified version of the MAX-PC (Memorial Anxiety Scale for Prostate Cancer) was used to determine cancer specific anxiety. Generalized estimating equations were applied to evaluate the association between anxiety and the duration on surveillance. Additionally, we examined associations between anxiety and patient age, marital status, Gleason score, the number of positive cores, family history and overall health. RESULTS: Median patient age was 61 years, median prostate specific antigen at diagnosis was 4.4 ng/ml and 95% of the patients had Gleason 6 disease. Median time from the initiation of active surveillance to the last survey was 3.7 years. There was a 29% risk of reporting cancer specific anxiety within year 1. Anxiety significantly decreased with time (OR 0.87, 95% CI 0.79-0.95, p = 0.003). Pathological and demographic characteristics were not associated with anxiety after adjusting for time on surveillance. CONCLUSIONS: In men undergoing active surveillance we observed a moderate risk of cancer specific anxiety which significantly decreases with time. Those considering conservative management can be informed that, although it is common to experience some anxiety initially, most patients rapidly adjust and report low anxiety levels within 2 years.

The natural history of large renal masses followed on observation.

PURPOSE: The safety and feasibility of active surveillance in comorbid patients with renal masses ≥4.0cm is uncertain. The aim of this study is to describe our institutional experience with the observation of large renal masses. MATERIALS AND METHODS: One hundred patients were identified with renal masses ≥ 4.0cm that were followed on observation for at least 6 months without surgical intervention between 1994 and 2016. Linear regression was conducted to determine predictors for renal mass growth and competing risk methods were used to estimate the probability of progression in the setting of death from other causes. RESULTS: Median age at diagnosis was 73 years and 73% of patients had a Charlson Comorbidity index ≥ 4. At presentation, the median mass size was 4.9cm. The median growth rate was 0.4cm/y and there were no significant predictors of growth. Surveillance was discontinued in 34 patients who underwent delayed intervention. Median follow up for metastasis-free survivors was 4 years. In total, 10 patients developed metastatic disease, 3 died from kidney cancer and 30 patients died from other causes. The 5-year probability of other cause mortality was 22% (95% CI: 14%-32%) compared to 6% (95% CI: 2%-13%) for metastatic progression of kidney cancer. CONCLUSION: In highly comorbid patients, the observation of large renal masses has low likelihood for metastatic progression relative to the risk of nonkidney cancer related death. This data supports the use of surveillance as an acceptable strategy for highly selected patients with competing risks from other serious illnesses.

Randomized Trial Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: Oncologic Outcomes.

BACKGROUND: Open radical cystectomy (ORC) has proven to be an important component in the treatment of high-risk bladder cancer (BCa). ORC surgical morbidity remains high; therefore, minimally invasive surgical techniques have been introduced in an attempt to improve patient outcomes. OBJECTIVE: To compare cancer outcomes in BCa patients managed with ORC or robotic-assisted radical cystectomy (RARC). DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized trial was completed between 2010 and 2013. Patients were randomized to ORC/pelvic lymphadenectomy (PLND) or RARC/PLND, with all undergoing open/extracorporeal urinary diversion. Median follow-up was 4.9 (IQR: 3.9-5.9) yr after surgery among surviving patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Secondary outcomes to the trial included recurrence-free, cancer-specific, and overall survival. RESULTS AND LIMITATIONS: The trial randomized 118 patients who underwent RC/PLND and urinary diversion. Sixty were randomized to RARC and 58 to ORC. Four RARC-assigned patients refused randomization and received ORC; however, an intention to treat analysis was performed. No differences were observed in recurrence (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 0.69-2.36; p=0.4) or cancer-specific survival (p=0.4). No difference in overall survival was observed (p=0.8). However, the pattern of first recurrence demonstrated a nonstatistically significant increase in metastatic sites for those undergoing ORC (sub-HR [sHR]: 2.21; 95% CI: 0.96-5.12; p=0.064) and a greater number of local/abdominal sites in the RARC-treated patients (sHR: 0.34; 95% CI: 0.12-0.93; p=0.035). The major limitation to this study is that the trial was not powered to determine differences in cancer recurrences, survival outcomes, or patterns of recurrence. CONCLUSIONS: The secondary outcomes from our randomized trial did not definitively demonstrate differences in cancer outcomes in patients treated with ORC or RARC. However, differences in observed patterns of first recurrence highlight the need for future studies. PATIENT SUMMARY: Of 118 patients randomly assigned to undergo radical cystectomy/pelvic lymphadenectomy and urinary diversion, half were assigned to open surgery and half to robot-assisted techniques. We found no difference in risk of recurring or dying of bladder cancer between the two groups.

Metastatic renal cell carcinoma to the testis: A case report and review of the literature.

This is a case of a 68-year-old male who presented with a chief compliant of a testicular mass, which was discovered to be a meta-static lesion of undiagnosed renal cell carcinoma. A computed tomography scan revealed a large right renal mass and multiple pulmonary metastasis. Shortly after diagnosis, the patient was initiated on systemic therapy and received a cytoreductive nephrectomy. We discuss the details of this case as well as a pertinent review of metastatic renal cell carcinoma to the testes.

The impact of vascular anastomosis time on early kidney transplant outcomes.

BACKGROUND: Most studies have found cold ischemic time to be an important predictor of delayed graft function in kidney transplantation. Relatively less is known about the warm time associated with vascular anastomosis and early outcomes. METHODS: A retrospective cohort of 298 consecutive solitary deceased donor kidney recipients from January 2006 to August 2012 was analyzed to examine the association between anastomosis time and delayed graft function (need for dialysis) and length of hospital stay. RESULTS: Delayed graft function (DGF) was observed in 56 patients (18.8%). The median anastomosis time was 30 minutes (interquartile range 24, 45 minutes). Anastomosis time was independently associated with DGF in a multivariable, binary logistic regression analysis (odds Ratio (OR) 1.037 per minute, 95% CI 1.016, 1.057, P = 0.001). An anastomosis time >29 minutes was also associated with a 3.5 fold higher (OR 3.5, 95% CI 1.6, 7.3, P = 0.001) risk of DGF. Median days in hospital was 9 (interquartile range 7, 14 days). Every 5 minutes of longer anastomosis time (0.20 days per minute, 95% CI 0.13, 0.27, P <0.001) was associated with 1 extra day in hospital in a multivariable linear regression model. An anastomosis time >29 minutes was associated with 3.8 (95% CI 1.6, 6.0, P <0.001) more days in hospital. CONCLUSION: Anastomosis time may be an underappreciated but modifiable variable in dictating use of hospital resources. The impact of anastomosis time on longer term outcomes deserves further study.

Blood transfusion in deceased donor kidney transplantation.

BACKGROUND: Given the unpredictable timing of deceased donor organs and the need for blood transfusion, this study was carried out to determine the rate and risk factors for transfusion in order to identifying a low-risk cohort in the face of a critical blood shortage. METHODS: This retrospective chart review examined 306 consecutive deceased solitary kidney transplant recipients from January 2006 to August 2012. RESULTS: Records show that 80 (26.1%) patients were transfused with a total of 300 units (0.98 units/transplant) during their first hospital stay. Transfusions were higher in patients on warfarin (8/14, 57%, 5.1 units/transplant) and antiplatelet agents (46/136, 33.8%, 1.1 unit/transplant) compared to no anticoagulants (74/156, 16.7%, 0.47 units/transplant). In a multivariable logistic regression analysis warfarin (odd ratio (OR) 8.2, 95% confidence interval (CI) 2.5-27, P=0.001), antiplatelet agents (OR 2.9, 95% CI 1.6-5.3, P=0.001), recipient age ≥55 years (OR 2.2, 95% CI 1.2-3.9, P=0.008), recipient male (OR 0.36, 95% CI 0.2-0.64, P=0.001) and preop hemoglobin ≥115 g/L (OR 0.32, 95% CI 0.18-0.57, P<0.001) were independent predictors of blood transfusion. Lower bleeding cohorts with transfusion rates <5% could not be identified. CONCLUSION: The need for blood is significantly higher in subjects on either warfarin or antiplatelet agents. These patients might be avoided if kidney transplantation is to occur during a critical blood shortage. Unfortunately even patients not on anticoagulation are at some risk.