Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study.

PURPOSE: Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS: Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS: In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION: This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Is intravesical prostatic protrusion a risk factor for hydronephrosis and renal insufficiency in benign prostate hyperplasia patients?

BACKGROUND: Some patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms hesitate to undergo surgical treatment until acute urinary retention (AUR) occurs. Some of these patients have been found to have hydronephrosis or even renal insufficiency. This study aimed to analyze the risk factors for hydronephrosis in patients with AUR who needed to receive transurethral resection of the prostate (TURP). METHODS: We retrospectively analyzed 91 patients from January 2014 to June 2015, who had BPH and received TURP for AUR. Patients with urolithiasis, prostate cancer, bladder cancer, gross hematuria, previous bladder radiation therapy, or urinary tract surgery were excluded. Parameters of intravesical prostatic protrusion (IPP), serum prostatic specific antigen (PSA), total prostate volume (PV), age, body mass index (BMI), hypertension (HTN), diabetes mellitus (DM), coronary artery disease (CAD), and serum creatinine (Cr) were compared between the hydronephrosis and non-hydronephrosis groups. RESULTS: There were significant differences in IPP (p < 0.001) and Serum Cr (p < 0.001) between the hydronephrosis and non-hydronephrosis groups. For IPP, the cut-off values of the highest risk of hydronephrosis was 1.95 cm. There were no significant differences in age, BMI, DM, HTN, CAD, total PV, and PSA between the two groups. IPP was not correlated with total PV (p = 0.423). Most of the patients with hydronephrosis had renal function improvement after TURP. CONCLUSION: IPP was a significant risk factor for hydronephrosis in BPH patients. If the patients' IPP exceeded 1.95 cm, they had a higher risk of having hydronephrosis when AUR occurred. Hydronephrosis is a risk factor for renal insufficiency, and Serum Cr levels decreased significantly in the patients of our study.

Vapoenucleation of the prostate using a high-power thulium laser: a one-year follow-up study.

BACKGROUND: Prostate vaporization and enucleation is a novel treatment option for bladder outlet obstruction caused by benign prostate enlargement. This surgical technique, however, has not yet been standardized. We present our findings of using a high-power thulium laser to accomplish vapoenucleation of the prostate (ThuVEP). METHODS: We prospectively collected and analyzed data from 29 patients who underwent ThuVEP between August 2010 and May 2012. The control group included 30 patients who underwent traditional transurethral resection of the prostate (TURP). Operative variables, patient profiles, preoperative and postoperative urine flow rates, prostate volume (measured using transrectal ultrasonography), and the international prostate symptom score (IPSS) were recorded and analyzed using a two-tailed Student's t-test and analysis of variance. RESULTS: The ages (mean ± SD) of the patients were 76.1 ± 9.4 and 72.6 ± 7.4 years (p = 0.28) in the ThuVEP and TURP groups, respectively. The average urinary flow rates before and 12 months after the operation (volume/maximum flow/average flow) were 243.3/10.5/5.0 and 302.8/17.6/9.4 (in mL, mL/s, mL/s, respectively) in the ThuVEP group and 247.2/10.8/4.6 and 369.9/20.8/12.0, respectively, in the TURP group. Preoperative and postoperative IPSSs were 17.1 ± 5.0 and 6.5 ± 3.8, respectively, in the ThuVEP group and 18.2 ± 4.5 and 6.2 ± 3.3, respectively, in the TURP group. The mean ratio of the estimated postoperative residual prostate volume to the preoperative total volume was 0.47 (p = 0.449) in both groups. The overall complication rate was 20.7% in the ThuVEP group and 30.0% in the TURP group. CONCLUSIONS: One year of follow-up showed that ThuVEP and TURP effectively alleviated subjective and objective voiding symptoms with a low rate of complications. Thus, vapoenucleation using a high-power laser is feasible in elderly patients. TRIAL REGISTRATION: ISRCTN registry with study ID ISRCTN52339705 . Date assigned: 06/03/2015.

Angiogenesis inhibitor therapies for advanced renal cell carcinoma: toxicity and treatment patterns in clinical practice from a global medical chart review.

The aim of this study was to assess the treatment patterns and safety of sunitinib, sorafenib and bevacizumab in real-world clinical settings in US, Europe and Asia. Medical records were abstracted at 18 community oncology clinics in the US and at 21 tertiary oncology centers in US, Europe and Asia for 883 patients ≥ 18 years who had histologically/cytologically confirmed diagnosis of advanced RCC and received sunitinib (n=631), sorafenib (n=207) or bevacizumab (n=45) as first-line treatment. No prior treatment was permitted. Data were collected on all adverse events (AEs) and treatment modifications, including discontinuation, interruption and dose reduction. Treatment duration was estimated using Kaplan-Meier analysis. Demographics were similar across treatment groups and regions. Median treatment duration ranged from 6.1 to 10.7 months, 5.1 to 8.5 months and 7.5 to 9.8 months for sunitinib, sorafenib and bevacizumab patients, respectively. Grade 3/4 AEs were experienced by 26.0, 28.0 and 15.6% of sunitinib, sorafenib and bevacizumab patients, respectively. Treatment discontinuations occurred in 62.4 (Asia) to 63.1% (US) sunitinib, 68.8 (Asia) to 90.0% (Europe) sorafenib, and 66.7 (Asia) to 81.8% (US) bevacizumab patients. Globally, treatment modifications due to AEs occurred in 55.1, 54.2 and 50.0% sunitinib, sorafenib and bevacizumab patients, respectively. This study in a large, global cohort of advanced RCC patients found that angiogenesis inhibitors are associated with high rates of AEs and treatment modifications. Findings suggest an unmet need for more tolerable agents for RCC treatment.

Diagnosis of prostate cancer: repeated transrectal prostate biopsy or transurethral resection.

BACKGROUND: Transrectal ultrasound-guided biopsy of the prostate is the major method by which prostate cancer is diagnosed. However, many patients might be overlooked with the initial biopsy. Not uncommonly, patients need repeated biopsies when they continue to exhibit suspicious clinical signs. This may cause psychological stress to both patients and doctors. The purpose of this study was to determine how many repeat transrectal biopsies are adequate for prostate cancer detection and when to switch to transurethral resection. METHODS: We retrospectively studied a cohort of 2,996 patients who had undergone prostate biopsy. If the biopsy specimen was negative for malignancy, patients were given the choice of either being managed with observation or undergoing transurethral resection of the prostate (TURP) if indicated. If there was a high suspicion of cancer, patients were advised to undergo additional biopsies. The primary endpoint of this study was a diagnosis of cancer. RESULTS: The cancer detection rate was 22.9% (685 of 2,996 patients) in specimens taken during the first transrectal biopsy, 8.7% in those taken during the second biopsy (32 of 336 patients), and 6.1% in those taken during the third biopsy (6 of 98 patients). The cancer detection rate of TURP after 1 negative biopsy result was 9.3% (35 of 375 patients), and that after 2 negative biopsy results was 17.1% (6 of 35 patients). TURP-derived specimens that were pathologically diagnosed as malignant had lower Gleason grade on average, no matter how many repeat biopsies there were in patients whose previous transrectal biopsy specimens were negative for malignancy (p=0.002 for 2 negative biopsy results and p=0.007 for 3 negative biopsy results). CONCLUSION: The chance of detecting malignancy beyond a third transrectal biopsy procedure is low. TURP, therefore, might be an alternative procedure for obtaining tissue for pathologic diagnosis, especially in patients with rising prostate-specific antigen levels and comorbid illnesses such as obstructive symptoms.

Transurethral prostatic resection for acute urinary retention in patients with prostate cancer.

BACKGROUND: Few studies have focused on clinical findings in prostate cancer patients receiving transurethral resection of the prostate (TURP) for acute urinary retention (AUR). We compared the clinical findings (preoperative characteristics, operative morbidities, and pathology results) of patients with diagnosed prostate cancer undergoing palliative TURP for AUR with those of patients undergoing TURP for AUR who were diagnosed with prostate cancer postoperatively. METHODS: The charts of 25 patients with prostate cancer undergoing TURP for AUR between 1986 and 2003 were retrospectively reviewed. Fourteen patients underwent palliative TURP (group A) and the other 11 patients with newly diagnosed prostate cancer received TURP (group B). The data, including preoperative characteristics, operative morbidities, and pathology results were analyzed. RESULTS: There were no significant differences between the 2 groups in parameters such as age at diagnosis and operation, operative time, hospitalization, and catheter duration. However, the Gleason score was higher in group A (7.6 +/- 1.7) than in group B (5.4 +/- 1.8) (p < 0.005). The mean resected weight was lower in group A (19.9 g) than in group B (39.5 g). Group A was more likely to receive recatheterization (33.3% vs 0%, p = 0.058) and repeat operation (28.6%), although the difference was not statistically significant. There were no complications such as transurethral resection syndrome or perioperative death in either group. CONCLUSION: TURP can be performed safely for relief of AUR in patients with prostate cancer, no matter if the cancer was diagnosed before or after surgery. The higher Gleason score and more advanced cancer stage, as found in group A, may correlate to high recatheterization and reoperation rates due to preexisting tumor progression.