Clinical translational research of liquid biopsy applications in prostate cancer and other urological cancers.

The aim of liquid biopsies is to obtain tumor information via the molecular interrogation of liquid samples, including blood and urine. As a minimally invasive procedure, liquid biopsies have attracted attention. A series of studies have reported associations of biomarkers such as circulating tumor DNA, cell-free DNA and extracellular vesicles with urological cancers, especially prostate cancer (PCa), and demonstrated the promising potential of liquid biopsies. In this review, we summarize recent clinical translational studies of liquid biopsies in PCa and other urological cancers, including bladder cancer and renal cell carcinoma. The number of translational studies was limited, and most of the studies focused on PCa. Biomarkers isolated from blood by different detection methods could be applied in clinical practice to predict prognosis and treatment response in advanced PCa. The other applications in urological cancers identified in previous studies remain to be explored further. Current studies are limited due to the lack of ideal standard detection methods for biomarkers. In the future, with advances in methodology, more translational studies will be conducted to identify potential applications of liquid biopsies in urological cancers.

Risk factors in the prediction of long-term patency of Resonance metallic ureteric stent in malignant ureteric obstruction.

Objectives: Cancer is the second leading cause of death globally in 2018 with an estimated 9.6 million deaths. The costs of managing malignant ureteric obstruction (MUO) is a significant burden to any healthcare system. However, the management of MUO has long been a challenge for urologists. The standard options of percutaneous nephrostomy or polymer double J stents are fraught with problems. We report a large patient series with long-term follow-up in the use of Resonance metallic ureteric stents to relieve MUO, and identification of risk factors associated with stent failure. Patients and methods: All patients with MUO who were arranged to have Resonance metallic ureteric stent insertion at two university hospitals were included in this cohort study, starting from June 2011 to July 2016. Data were retrieved retrospectively. The primary outcome was the total duration of stent patency before stent failure due to malignant disease progression. Stent failure was defined as ureteric obstruction identified on imaging (functional radioisotope scan or antegrade pyelogram), acute renal failure resolved by subsequent percutaneous nephrostomy, or any other cause requiring stent removal prematurely. Secondary outcomes were identification of factors associated with stent failure, grade III or above complication, and development of a risk-adopted model to predict metallic ureteric stent patency rates in MUO patients. Median duration of functioning metallic ureteric stent was determined with Kaplan-Meier survival curve. Results: A total of 124 renal units in 95 patients with MUO were eligible for the study, with a median follow-up period of 22.9 months. About 106 (85.5%) renal units had successful metallic stent insertion, of whom 41 (33.1%) renal units ultimately progressed to ureteric obstruction despite the metallic stents, and required subsequent insertion of nephrostomies. Median duration of functioning metallic ureteric stents was 25 months. Female gender (HR 3.0, 95% CI: 1.3-7.2, P = .014) and suspicious bladder lesion (HR 2.9, 95% CI: 1.4-6.2, P = .005) were independent risk factors for stent failure, respectively. Stratifying patients into low (0 risk factor), intermediate (1 risk factor), and high (2 risk factors) risk groups, we found that this could predict the duration of stent patency in MUO with the metallic stents. (Low risk: 30.3 months vs intermediate group: 17.8 months vs high risk: 4.9 months, P < .001). Conclusion: Resonance metallic ureteral stents are able provide a median of 25 months of ureteric drainage in patients with MUO. Determining whether a patient has one or both risks factors (female gender and bladder lesion) will allow one to estimate the duration of metallic stent patency, which in turn may aid in determining cost-effectiveness in individual patients.

Is prostate specific antigen (PSA) density necessary in selecting prostate cancer patients for active surveillance and what should be the cutoff in the Asian population?

BACKGROUND: To investigate the role of Prostate Specific Antigen density (PSAD) in selecting prostate cancer patients for active surveillance (AS) and to determine a cutoff PSAD in identifying adverse pathological outcomes. METHODS: Data from 287 patients who underwent radical prostatectomy for prostate cancer were retrospectively reviewed. Six different AS protocols, the University of Toronto; Royal Marsden; John Hopkins; University of California San Francisco (UCSF); Memorial Sloan Kettering Cancer Center (MSKCC) and Prostate Cancer Research International: Active Surveillance (PRIAS), were applied to the cohort. Pre-operative demographics and pathological outcomes were analysed. Statistical analyses on the predictive factors of adverse pathological outcomes and significance of PSAD were performed. A cutoff PSAD with best balance between sensitivity and specificity in identifying adverse pathological outcome was determined. RESULTS: PSAD predicted adverse pathological outcomes better than Prostate Specific Antigen (PSA) level alone. The PSAD was significantly lower (0.12-0.13 ng/dl/ml) in protocols including PSAD (the John Hopkins and PRIAS) compared with the other four protocols not including PSAD as a selection criteria (0.21-0.25 ng/dl/dl, P = 0.00). PSAD predicted adverse pathological outcomes in all protocols not incorporating PSAD as an inclusion criteria (P = 0.00-0.02). By the receiver operator characteristics curve analysis, it was found that a PSAD level of 0.19 ng/ml/ml had the best balance between sensitivity and specificity in predicting pathological adverse disease (Area under curve = 0.63, P = 0.004). CONCLUSION: PSAD is necessary in selecting prostate cancer patients for active surveillance. It predicts adverse pathological outcomes in patients eligible for active surveillance better than PSA level alone. A PSAD cutoff at 0.19 ng/ml/ml has the best balance between sensitivity and specificity in predicting pathological adverse disease. We recommend using AS protocol incorporating PSAD as a selection criteria (in particular the PRIAS protocol with a cutoff PSAD at 0.2 ng/ml/ml) when recruiting prostate cancer patients for AS.

Psychometric properties of Functional Assessment of Cancer Therapy-Prostate (FACT-P) in Chinese patients with prostate cancer.

PURPOSE: The aim of the study was to assess the validity, reliability and sensitivity of the FACT-P (version 4) in Chinese males with prostate cancer. METHODS: Construct validity was assessed using Spearman's correlation test against the 12-item Short Form Health Survey (SF-12v2). Internal consistency and test-retest reliability were assessed using Cronbach's α coefficient and intra-class correlation coefficient, respectively. Sensitivity was determined by performing known-group comparisons by independent t test. RESULTS: FACT-P subscale scores had a moderate correlation with the corresponding SF-12v2 domain score that conceptually measures the similar construct providing evidence for adequate construct validity. Internal consistency was acceptable (α: 0.687-0.900) for all subscales aside from the Prostate Cancer Subscale (α: 0.505) and Trial Outcome Index (α: 0.562). FACT-P subscale and total scores showed good test-retest reliability (range 0.753-0.913). All total scales and most of the subscales were sensitive in detecting differences between patients with different levels of functional impairment but not different cancer stages or levels of prostate-specific antigen. CONCLUSIONS: The measure is a valid and reliable measure to assess the health-related quality of life of Chinese males with prostate cancer. The FACT-P is sensitive to detect difference between patients with varying functional status.

Current status of robot-assisted surgery.

The introduction of robot-assisted surgery, and specifically the da Vinci Surgical System, is one of the biggest breakthroughs in surgery since the introduction of anaesthesia, and represents the most significant advancement in minimally invasive surgery of this decade. One of the first surgical uses of the robot was in orthopaedics, neurosurgery, and cardiac surgery. However, it was the use in urology, and particularly in prostate surgery, that led to its widespread popularity. Robotic surgery, is also widely used in other surgical specialties including general surgery, gynaecology, and head and neck surgery. In this article, we reviewed the current applications of robot-assisted surgery in different surgical specialties with an emphasis on urology. Clinical results as compared with traditional open and/or laparoscopic surgery and a glimpse into the future development of robotics were also discussed. A short introduction of the emerging areas of robotic surgery were also briefly reviewed. Despite the increasing popularity of robotic surgery, except in robot-assisted radical prostatectomy, there is no unequivocal evidence to show its superiority over traditional laparoscopic surgery in other surgical procedures. Further trials are eagerly awaited to ascertain the long-term results and potential benefits of robotic surgery.