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1.
J Urol ; : 101097JU0000000000000565, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549935

RESUMO

PURPOSE: The randomized open versus robotic cystectomy (RAZOR) trial reported non-inferior 2-year progression-free survival (PFS) for robotic radical cystectomy (RARC). This update was performed with extended follow-up for 3 years to demonstrate potential differences between the approaches. We also report 3-year overall survival (OS) and aim to identify factors predicting recurrence, PFS and OS. MATERIALS AND METHODS: The per-protocol population of 302 patients from RAZOR study was analyzed. Cumulative recurrences were estimated using non-bladder cancer death as the competing risk event and Gray's test was used to assess significance in differences. PFS and OS were estimated by Kaplan-Meier method and compared using the log rank test. Predictors of outcomes were determined by Cox proportional hazard analysis. RESULTS: Estimated PFS at 36 months was 68.4% (95% CI 60.1-75.3%) and 65.4% (95% CI 56.8-72.7%) in the robotic and open groups respectively (p=0.600). OS at 36 months was 73.9% (95% CI 65.5-80.5%) and 68.5% (95% CI 59.8-75.7%) for the robotic and open group respectively (p=0.334). There was no significant difference in the cumulative incidence rates of recurrence (p=0.802). Age >70 years, poor performance status and major complications were significant predictors of PFS and OS. Stage and positive margins were significant predictors of recurrence, PFS and OS. Surgical approach was not a significant predictor of any outcome. CONCLUSIONS: This analysis shows no difference in recurrence, 3-year PFS and 3-year OS between RARC and ORC. It provides important prospective data on the oncologic efficacy of RARC and high-level data for patient counseling.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31350101

RESUMO

OBJECTIVES: To assess the utility of multiparametric MRI in detecting clinically significant prostate cancer (csPCa) by comparing PI-RADSv2 scores with International Society of Urological Pathology (ISUP) pathologic grading criteria. METHODS: Data from 137 patients were retrospectively analyzed. PI-RADSv2 scores were compared with pathologic grade using ISUP criteria. Pathologic grades were divided into clinically significant (groups 3-5) and clinically insignificant lesions (groups 1-2). Chi-squared analysis was performed for to assess correlation. RESULTS: Sensitivity and specificity of PI-RADSv2 score 3-5 lesions for detecting csPCa was 100% and 18.5%, respectively. Negative predictive value (NPV) is 100% for these lesions. When considering only PI-RADSv2 score 4-5 lesions, sensitivity decreases to 90% and specificity increases to 67.5%, with a NPV of 98.5%. When only PI-RADSv2 score 5 lesions are considered, sensitivity decreases to 50% and specificity increases to 90%, with a NPV of 95%. CONCLUSIONS: Multiparametric MRI has excellent sensitivity for detecting csPCa. Specificity is poor for PI-RADSv2 score 3 lesions but improves significantly for PI-RADSv2 score 4 and 5 lesions. Overall, mpMRI is an excellent screening tool for csPCa, as designated by the recently validated ISUP criteria. ADVANCES IN KNOWLEDGE: Multiple limitations of the longstanding Gleason pathologic scoring system have led to the development of new ISUP pathologic criteria, which is more focused on the clinical significance of lesions. There are currently insufficient studies evaluating and validating the ISUP criteria with PIRADS v2 evaluation of the prostate.

3.
Urology ; 129: 1-7, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059728

RESUMO

OBJECTIVE: To report 12-month safety and effectiveness outcomes of the Aquablation procedure for the treatment of men with symptomatic benign prostatic hyperplasia (BPH) and large-volume prostates. METHODS: One hundred and one men with moderate-to-severe BPH symptoms and prostate volumes of 80-150 cc underwent a robotic-assisted Aquablation procedure in a prospective multicenter international clinical trial. Functional and safety outcomes were assessed at 12 months postoperatively. RESULTS: Mean prostate volume was 107 cc (range 80-150). Mean operative time was 37 minutes and mean Aquablation resection time was 8 minutes. The average length of hospital stay following the procedure was 1.6 days. Mean International Prostate Symptom Score improved from 23.2 at baseline to 6.2 at 12 months (P <.0001). Mean International Prostate Symptom Score quality of life improved from 4.6 at baseline to 1.3 at 12-month follow-up (P <.0001). Significant improvements were seen in Qmax (12-month improvement of 12.5 cc/sec) and postvoid residual (drop of 171 cc in those with postvoid residual >100 at baseline). Antegrade ejaculation was maintained in 81% of sexually active men. No patient underwent a repeat procedure for BPH symptoms. There was a 2% de novo incontinence rate at 12 months, and 10 patients did require a transfusion postoperatively while 5 required take back fulgurations. At 12 months, prostate-specific antigen reduced from 7.1 ± 5.9 ng/mL at baseline to 4.4 ± 4.3 ng/mL. CONCLUSION: The Aquablation procedure is demonstrated to be safe and effective in treating men with large prostates (80-150 cc) after 1 year of follow-up, with an acceptable complication rate and without a significant increase in procedure or resection time compared to smaller sized glands. ClinicalTrials.gov number, NCT03123250.

4.
Cell Commun Signal ; 17(1): 25, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885218

RESUMO

BACKGROUND: Flavokawain B (FKB) has been identified from kava root extracts as a potent apoptosis inducer for inhibiting the growth of various cancer cell lines, including prostate cancer. However, the molecular targets of FKB in prostate cancer cells remain unknown. METHODS: An in vitro NEDD8 Initiation Conjugation Assay was used to evaluate the neddylation inhibitory activity of FKB. Molecular docking and a cellular thermal shift assay were performed to assess the direct interaction between FKB and the NEDD8 activating enzyme (NAE) complex. Protein neddylation, ubiqutination, stability and expression in cells were assessed with immunoprecipitation and Western blotting methods using specific antibodies. Deletion and site specific mutants and siRNAs were used to evaluate deep mechanisms by which FKB induces Skp2 degradation. Cell growth inhibition and apoptosis induction were measured by MTT, ELISA and Western blotting methods. RESULTS: FKB inhibits NEDD8 conjugations to both Cullin1 and Ubc12 in prostate cancer cell lines and Ubc12 neddylation in an in vitro assay. Molecular docking study and a cellular thermal shift assay reveal that FKB interacts with the regulatory subunit (i.e. APP-BP1) of the NAE. In addition, FKB causes Skp2 degradation in an ubiquitin and proteasome dependent manner. Overexpression of dominant-negative cullin1 (1-452), K720R mutant (the neddylation site) Cullin1 or the F-box deleted Skp2 that losses its binding to the Skp1/Cullin1 complex causes the resistance to FKB-induced Skp2 degradation, whereas siRNA knock-down of Cdh1, a known E3 ligase of Skp2 for targeted degradation, didn't attenuate the effect of FKB on Skp2 degradation. These results suggest that degradation of Skp2 by FKB is involved in a functional Cullin1. Furthermore, proteasome inhibitors Bortezomib and MG132 transcriptionally down-regulate the expression of Skp2, and their combinations with FKB result in enhanced inhibitory effects on the growth of prostate cancer cell lines via synergistic down-regulation of Skp2 and up-regulation of p27/Kip1 and p21/WAF1 protein expression. FKB also selectively inhibits the growth of RB deficient cells with high expression of Skp2. CONCLUSION: These findings provide a rationale for further investigating combination of FKB and Bortezomib for treatment of RB deficient, castration-resistant prostate cancer.


Assuntos
Antineoplásicos/farmacologia , Bortezomib/farmacologia , Flavonoides/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Proteínas Quinases Associadas a Fase S/metabolismo , Antígenos CD/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Bortezomib/uso terapêutico , Caderinas/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteínas Culina/metabolismo , Flavonoides/uso terapêutico , Humanos , Leupeptinas/farmacologia , Leupeptinas/uso terapêutico , Masculino , Proteína NEDD8/metabolismo , Células PC-3 , Enzimas Ativadoras de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo
5.
BJU Int ; 124(2): 321-328, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30734990

RESUMO

OBJECTIVE: To present 6-month safety and effectiveness data from a multicentre prospective study of aquablation in men with lower urinary tract symptoms (LUTS) attributable to benign prostatic hyperplasia (BPH) with prostate volumes between 80 and 150 mL. METHODS: Between September and December 2017, 101 men with LUTSattributable to BPHwere prospectively enrolled at 16 centres in Canada and the USA. RESULTS: The mean prostate volume was 107 mL. The mean length of hospital stay after the aquablation procedure was 1.6 days (range: same day to 6 days). The primary safety endpoint (Clavien-Dindo grade 2 or higher or any grade 1 event resulting in persistent disability) at 3 months occurred in 45.5% of men, which met the study design goal of < 65% (P < 0.001). At 6 months, 22% of the patients had experienced a Clavien-Dindo grade 2, 14% a grade 3 and 5% a grade 4 adverse event. Bleeding complications requiring intervention and/or transfusion were recorded in eight patients prior to discharge and in six patients after discharge. The mean International Prostate Symptom Score improved from 23.2 ± 6.3 at baseline to 6.7 ± 5.1 at 3 months, meeting the study's primary efficacy endpoint goal (P < 0.001). The maximum urinary flow rate increased from 8.7 to 18.8 mL/s (P < 0.001) and post-void residual urine volume decreased from 131 at baseline to 47 at 6 months (P < 0.0001). At 6 months, prostate-specific antigen concentration reduced from 7.1 ± 5.9 ng/mL at baseline to 4.0 ± 3.9 ng/mL, a 44% reduction. CONCLUSIONS: Aquablation is safe and effective in treating men with larger prostates (80-150 mL), without significant increase in procedure or resection time.

6.
J Investig Med ; 66(8): 1142-1146, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30297390

RESUMO

Older men are more likely to have advanced prostate cancer at time of their diagnosis, but whether prostate tumors are inherently (biologically) more aggressive with advancing age is uncertain. To address this gap in knowledge, we analyzed data from veterans (n=971) diagnosed with prostate cancer during 1991-1995. Factors included age, detection of prostate cancer by screening, prostate-specific antigen (PSA) level, anatomic stage, and Gleason score. Information on molecular markers obtained from immunohistochemical staining of prostate tissue, included B cell lymphoma-2 (bcl-2), p53, and microvessel density (MVD), each having a previously documented association with disease progression and increased risk of prostate cancer death. We first examined the bivariate association of demographic, clinical, and molecular factors with age, and found evidence that race, screening status, Gleason score, PSA, bcl-2, p53, and MVD varied across categories of age in this study population. After further characterizing the association between age and Gleason score, we used logistic regression to examine the association between age and molecular markers-accounting for race, screening status, PSA, and Gleason score. Comparing men older than 80 years to those younger than 70 years, adjusted ORs and 95% CIs were 1.89 (0.73 to 4.92), 1.91 (1.05 to 3.46), and 2.00 (1.06 to 3.78), for positive bcl-2, p53, and MVD markers, respectively; no statistically significant associations were found for men 70-79 years old, compared with men younger than 70 years. These novel findings suggest that very elderly men often present with biologically aggressive prostate cancer; the results also have potential implications for therapeutic decision-making.

7.
Eur Urol Focus ; 2018 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-30197041

RESUMO

The Immunotherapy to Prevent Progression on Active Surveillance Study is the first trial of immunotherapy for localized prostate cancer. We randomized active surveillance patients to PSA-TRICOM (PROSTVAC) or placebo for 5mo. Final results will be available in 2019.

8.
Lancet ; 391(10139): 2525-2536, 2018 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-29976469

RESUMO

BACKGROUND: Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy. METHODS: The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676. FINDINGS: Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI -9·6% to 10·9%; pnon-inferiority=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group). INTERPRETATION: In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types. FUNDING: National Institutes of Health National Cancer Institute.

9.
Br J Radiol ; 91(1088): 20180091, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29869921

RESUMO

OBJECTIVE: The aim of this study is to evaluate the utility of quantitative apparent diffusion coefficient (ADC) measurements and normalized ADC ratios in multiparametric MRI for the diagnosis of clinically significant peripheral zone (PZ) prostate cancer particularly among equivocally suspicious prostate lesions. METHODS: A retrospective analysis of 95 patients with PZ lesions by PI-RADSv2 criteria, and who underwent subsequent MRI-US fusion biopsy, was approved by an institutional review board. Two radiologists independently measured ADC values in regions of interest (ROIs) of PZ lesions and calculated normalized ADC ratio based on ROIs in the bladder lumen. Diagnostic performance was evaluated using ROC. Inter observer variability was assessed using intraclass correlation coefficient (ICC). RESULTS: Mean ADC and normalized ADC ratios for clinically significant and non-clinically significant lesions were 0.763 × 10-3 mm2 s-1, 29.8%; and 1.135 × 10-3 mm2 s-1, 47.2% (p < 0.001), respectively. Area under the ROC curve (AUC) was 0.880 [95% CI (0.816-0.944) and 0.885 (95% CI (0.814-0.955)] for ADC and ADC ratio, respectively. Optimal AUC threshold for ADC was 0.843 × 10-3 mm2 s-1 (Sn 70.5%, Sp 88.2%) and for normalized ADC was 33.1% (Sn 75.0%, Sp 95.7%). intraclass correlation coefficient was high at 0.889. CONCLUSION: Quantitative ADC measurement in PZ prostate lesions demonstrates excellent diagnostic performance in differentiating clinically significant from non-clinically significant prostate cancer with high inter observer correlation. Advances In knowledge: Quantitative ADC is presented as an additional method to evaluate lesions in mpMRI of the prostate. This technique may be incorporated in new and existing methods to improve detection and discrimination of clinically significant prostate cancer.


Assuntos
Imagem por Ressonância Magnética , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Urology ; 117: 89-94, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29630955

RESUMO

OBJECTIVE: To compare the performance of 3 contemporary ureteroscopic biopsy devices for the histopathologic diagnosis of upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively reviewed 145 patients who underwent 182 urothelial biopsies using 2.4F backloaded cup biopsy forceps, a nitinol basket, or 3F standard cup biopsy forceps at 3 tertiary academic centers between 2011 and 2016. Experienced genitourinary pathologists provided an assessment of each specimen without knowledge of the device used for biopsy. For patients who underwent nephroureterectomy without neoadjuvant chemotherapy within 3 months of biopsy-proven UTUC diagnosis, the biopsy grade was compared with both the grade and stage of the surgical specimen. RESULTS: Biopsy utilization varied among the 3 institutions (P <.0001). Significant variabilities in specimen size (P = .001), the presence of intact urothelium (P = .008), and crush artifact (P = .028) were found among the biopsy devices. The quality of specimens from backloaded cup forceps was rated similarly to the nitinol basket (P >.05) and was favored over standard cup forceps specimens. Grade concordance was not affected by specimen size (P >.05), morphology (P >.1), or location (P >.5). No difference existed among the devices in the rate of acquiring a grade concordant biopsy; however, the backloaded cup forceps provided concordant biopsies that could be distinguished as low- and high-grade (P = .02). CONCLUSION: The backloaded cup forceps and nitinol basket obtained a higher quality urothelial specimen compared with standard cup forceps. Ureteroscopic biopsy device selection did not significantly impact the accuracy of the histologic diagnosis of UTUC.

11.
BJU Int ; 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29694702

RESUMO

OBJECTIVES: To present early safety and feasibility data from a multicentre prospective study (WATER II) of aquablation in the treatment of symptomatic men with large-volume benign prostatic hyperplasia (BPH). METHODS: Between September and December 2017, 101 men with moderate-to-severe BPH symptoms and prostate volume of 80-150 mL underwent aquablation in a prospective multicentre international clinical trial. Baseline demographics and standardized postoperative management variables were carefully recorded in a central independently monitored database. Surgeons answered analogue scale questionnaires on intra-operative technical factors and postoperative management. Adverse events up to 1 month were adjudicated by an independent clinical events committee. RESULTS: The mean (range) prostate volume was 107 (80-150) mL. The mean (range) operating time was 37 (15-97) min and aquablation resection time was 8 (3-15) min. Adequate adenoma resection was achieved with a single pass in 34 patients and with additional passes in 67 patients (mean 1.8 treatment passes), all in a single operating session. Haemostasis was achieved using either a Foley balloon catheter placed in the bladder under traction (n = 98, mean duration 18 h) or direct tamponade using a balloon inflated in the prostate fossa (n = 3, mean duration 15 h). No patient required electrocautery for haemostasis at the time of the primary procedure. The mean length of stay after the procedure was 1.6 days (range same day to 6 days). The Clavien-Dindo grade ≥2 event rate observed at 1 month was 29.7%. Bleeding complications were recorded in 10 patients (9.9%) during the index procedure hospitalization prior to discharge, and included six (5.9%) peri-operative transfusions. CONCLUSIONS: Aquablation is feasible and safe in treating men with men with large prostates (80-150 mL). The 6-month efficacy data are being accrued and will be presented in future publications (ClinicalTrials.gov number, NCT03123250).

12.
Prostate ; 78(4): 294-299, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29315679

RESUMO

BACKGROUND: Distinguishing between low- and high-grade prostate cancers (PCa) is important, but biopsy may underestimate the actual grade of cancer. We have previously shown that urine/plasma-based prostate-specific biomarkers can predict high grade PCa. Our objective was to determine the accuracy of a test using cell-free RNA levels of biomarkers in predicting prostatectomy results. METHODS: This multicenter community-based prospective study was conducted using urine/blood samples collected from 306 patients. All recruited patients were treatment-naïve, without metastases, and had been biopsied, designated a Gleason Score (GS) based on biopsy, and assigned to prostatectomy prior to participation in the study. The primary outcome measure was the urine/plasma test accuracy in predicting high grade PCa on prostatectomy compared with biopsy findings. Sensitivity and specificity were calculated using standard formulas, while comparisons between groups were performed using the Wilcoxon Rank Sum, Kruskal-Wallis, Chi-Square, and Fisher's exact test. RESULTS: GS as assigned by standard 10-12 core biopsies was 3 + 3 in 90 (29.4%), 3 + 4 in 122 (39.8%), 4 + 3 in 50 (16.3%), and > 4 + 3 in 44 (14.4%) patients. The urine/plasma assay confirmed a previous validation and was highly accurate in predicting the presence of high-grade PCa (Gleason ≥3 + 4) with sensitivity between 88% and 95% as verified by prostatectomy findings. GS was upgraded after prostatectomy in 27% of patients and downgraded in 12% of patients. CONCLUSIONS: This plasma/urine biomarker test accurately predicts high grade cancer as determined by prostatectomy with a sensitivity at 92-97%, while the sensitivity of core biopsies was 78%.

13.
J Urol ; 199(6): 1459-1463, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29223389

RESUMO

PURPOSE: The 4Kscore® test accurately detects aggressive prostate cancer and reduces unnecessary biopsies. However, its performance in African American men has been unknown. We assessed test performance in a cohort of men with a large African American representation. MATERIALS AND METHODS: Men referred for prostate biopsy at 8 Veterans Affairs medical centers were prospectively enrolled in the study. All men underwent phlebotomy for 4Kscore test assessment prior to prostate biopsy. The primary outcome was the detection of Grade Group 2 or higher cancer on biopsy. We assessed the discrimination, calibration and clinical usefulness of 4Kscore to predict Grade Group 2 or higher prostate cancer and compared it to a base model consisting of age, digital rectal examination and prostate specific antigen. Additionally, we compared test performance in African American and nonAfrican American men. RESULTS: Of the 366 enrolled men 205 (56%) were African American and 131 (36%) had Grade Group 2 or higher prostate cancer. The 4Kscore test showed better discrimination (AUC 0.81 vs 0.74, p <0.01) and higher clinical usefulness on decision curve analysis than the base model. Test prediction closely approximated the observed risk of Grade Group 2 or higher prostate cancer. There was no difference in test performance in African American and nonAfrican American men (0.80 vs 0.84, p = 0.32), The test outperformed the base model in each group. CONCLUSIONS: The 4Kscore test accurately predicts aggressive prostate cancer for biopsy decision making in African American and nonAfrican American men.

14.
J Investig Med ; 66(4): 768-772, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29170243

RESUMO

Prostate-specific antigen (PSA) measurements after primary treatment reflect residual tumor burden among men with prostate cancer. Using a mixture model analysis, we identified distinct trajectories of post-treatment PSA measurements and evaluated their associations with prostate cancer mortality. The study sample included 623 US Veterans treated for prostate cancer with curative intent during 1991-1995; 225 men received surgery and 398 men received radiation therapy. Post-treatment PSA measurements over a 2-year period for each patient were evaluated in latent class mixture models using the SAS TRAJ procedure, and groups of men with distinct trajectories of PSA were identified. These groups were then assessed for associations with 10-year prostate cancer mortality using proportional hazards analysis. Analyses identified three distinct groups-representing patterns of both initial values and changes in PSA over time-after surgery (n=172/31/14) and radiation therapy (n=253/103/22). Men in groups with patterns of higher (compared with the group with lowest) PSA values tended to have worse survival experience: HRs for prostate cancer mortality were 3.45 (P=0.18) and 22.7 (P<0.001) for surgery, and 2.70 (P=0.005) and 18.1 (P<0.001) for radiation therapy. The results indicate that PSA measurements after surgery or radiation therapy with curative intent include groups of men with a diverse spectrum of prognosis for prostate cancer mortality. Although contemporary PSA levels are lower than those observed in the study sample, the corresponding trajectory patterns may become evident shortly after the time of diagnosis and treatment.

15.
J Clin Oncol ; 36(6): 581-590, 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29185869

RESUMO

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.

16.
Curr Probl Diagn Radiol ; 47(6): 404-409, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29126575

RESUMO

PURPOSE: Use of magnetic resonance imaging (MRI)/transrectal ultrasound fusion biopsies to determine the accuracy of multiparametric MRI (mpMRI), using Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2), for detecting clinically significant prostate cancer in the overall gland and specifically the peripheral zone (PZ) and transitional zone (TZ). METHODS: A retrospective analysis of patients who underwent fusion biopsy identified 137 men with 231 prostate lesions was approved by the Institutional Review Board. Subjects initially classified under PI-RADSv1 criteria were regraded using PI-RADSv2 by a radiologist blinded to PI-RADSv1 score and biopsy results. Spearman correlation, chi-squared, and logistic regression analysis were performed. RESULTS: There was positive correlation between PI-RADSv2 and Gleason scores (P < 0.001). In the PZ, mpMRI demonstrated 100% sensitivity, 100% negative predictive value, and 35.9% positive predictive value, compared to 100%, 100%, and 27.1%, respectively, for TZ lesions. When predicting clinically significant prostate cancer, the PI-RADSv2 area under the curve for TZ lesions was 0.844 (95% CI: 0.753-0.935, P < 0.001) and 0.769 (95% CI: 0.684-0.854, P < 0.001) for PZ lesions. Combining PI-RADSv2 with additional risk factors (body mass index, prostate-specific antigen density, digital rectal examination) improved the area under curve. CONCLUSIONS: PI-RADSv2 achieves excellent sensitivity and negative predictive value for both PZ and TZ lesions.

17.
J Cancer ; 8(13): 2554-2560, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28900493

RESUMO

Background: Unnecessary biopsies and overdiagnosis of prostate cancer (PCa) remain a serious healthcare problem. We have previously shown that urine- and plasma-based prostate-specific biomarkers when combined can predict high grade prostate cancer (PCa). To further validate this test, we performed a prospective multicenter study recruiting patients from community-based practices. Patients and Methods: Urine and plasma samples from 2528 men were tested prospectively. Results were correlated with biopsy findings, if a biopsy was performed as deemed necessary by the practicing urologist. Of the 2528 patients, biopsy was performed on only 524 (21%) patients. Results: Of the 524 patients, Gleason≥3+4 PCa was found in 161 (31%) and Gleason ≥4+3 was found in 62 (12%) of the patients. The urine/plasma biomarkers algorithm showed sensitivity and specificity of 75% and 69% for predicting Gleason ≥3+4. However, upon incorporating prostate size and prior history of biopsy in the algorithm, we achieved a sensitivity between 97% and 86% and a specificity between 36% and 57%, dependent on the used cut-off point. Sensitivity for predicting PCa Gleason ≥4+3 was between 96% and 99% and specificity between 59% and 37%, dependent on the cut-off point. Diagnosis of Gleason ≥3+4 was missed in 1% to 3% of tested patients and of Gleason ≥4+3 in 0.2% to 1%. Conclusion: This test when integrated with prostate volume and the prior prostate biopsy enhance the sensitivity and specificity for predicting the presence of high grade prostate cancer with negative predictive value (NPV) of 90% to 97% for Gleason ≥3+4 and between 98% to 99% for Gleason ≥4+3.

18.
Urol Oncol ; 35(5): 192-200, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28041996

RESUMO

INTRODUCTION: Evidence for the use of perioperative chemotherapy (PC) in upper tract urothelial carcinoma (UTUC) is largely derived from level I evidence for invasive urothelial carcinoma of the bladder (UCB). There has been an increase in PC for urothelial carcinoma of the bladder, as it has disseminated into clinical practice. Therefore, we sought to not only analyze trends in the utilization of PC in UTUC, but also assess factors associated with its use in a large cancer registry database. METHODS: The National Cancer Database was queried for patients with UTUC who underwent extirpative surgery from 2004 to 2013. Predictors of receiving PC were identified using univariate and multivariate logistic regression. Temporal trends in the utilization of PC were also analyzed using a general analysis of variance linear model. RESULTS: From 2004 to 2013, there was significant increase in PC for UTUC from 9.6% to 13.8% (P = 0.0003). Neoadjuvant chemotherapy increased from 0.7% to 2.1% (P = 0.0018), whereas adjuvant chemotherapy remained relatively stable at 11.3%. Significant predictors of receiving PC on multivariate analysis were private insurance, ureter as the primary site, poorly differentiated and undifferentiated grade, lymphovascular invasion, positive margins, clinical T3 or T4 disease, nodal metastasis, and reporting from an academic research program. Patients who were≥70 years old,>50 miles to treatment center, had tumor in the kidney, or had an increased Charlson-Deyo Score were significantly less likely to receive PC. CONCLUSIONS: Over the time period studied, there has been an increase in the use of PC, primarily from increased administration of neoadjuvant chemotherapy. Its use is mostly associated with advanced pathologic characteristics. The study also highlights key demographic and socioeconomic differences that can help identify barriers to receiving PC and aid in making improvements in delivery of health care to patients with UTUC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Ureterais/tratamento farmacológico , Neoplasias Ureterais/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante/tendências , Feminino , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Seguro Saúde , Neoplasias Renais/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/tendências , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasia Residual , Período Perioperatório , Sistema de Registros , Estados Unidos , Neoplasias Ureterais/cirurgia , Adulto Jovem
19.
J Endourol ; 31(1): 7-13, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27784185

RESUMO

PURPOSE: To determine the incidence and predictors of major complications in patients undergoing percutaneous cryoablation (PCA) for small renal masses. METHODS: We performed a retrospective analysis of patients undergoing PCA from 2005 to 2012. We analyzed demographic, radiographic, and complication data. We defined complications as any deviation from the expected postoperative course. We determined predictors of complications. RESULTS: A total of 190 patients were included in the study. The mean age was 69 years, and 132 (69%) were males. The mean tumor diameter was 2.2 cm (0.8-4.0 cm). The mean number of probes utilized per procedure was 2.3. We observed 16 (8.4%) complications including 14 Clavien grade I, which includes 6 (2%) large renal/retroperitoneal hematomas, 4 (2%) pneumothoraxes, 2 (1%) urinary tract infections, and 2 (1%) atrial fibrillations. There were two (1%) Clavien grade II complications (intestinal perforations). In univariable analysis, larger tumors and more probes were associated with higher risk of complications (all ps < 0.05). In multivariable analysis, larger tumor dimension (odds ratio [OR] = 2.85; 95% confidence interval [CI] = 1.34, 6.05; p = 0.006) was independently associated with major complications. After multivariable adjustments for patient's characteristics such as age, gender, American Society of Anesthesiologists, year of surgery, and histopathology, larger tumor dimension (OR = 2.85; 95%CI = 1.34, 6.05; p = 0.006) and more cryoablation probes (OR = 1.94; 95%CI = 1.36, 2.75; p < 0.001) were independently associated with higher risk of major complications. CONCLUSIONS: In a cohort of patients undergoing PCA for T1a small renal mass, larger tumor dimension and more cryoablation probes were independently associated with higher risk of complication. Although PCA is relatively safe and the major complications are infrequent, careful patient selection is crucial.


Assuntos
Criocirurgia/instrumentação , Criocirurgia/métodos , Córtex Renal/cirurgia , Neoplasias Renais/cirurgia , Idoso , Algoritmos , Feminino , Humanos , Incidência , Córtex Renal/patologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
Curr Pharmacol Rep ; 3(6): 384-395, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30393593

RESUMO

Purpose of review: Rhodiola rosea extracts have been used as a dietary supplement in healthy populations, including athletes, to non-specifically enhance the natural resistance of the body to both physical and behavior stresses for fighting fatigue and depression. We summarize the information with respect to the new pharmacological activities of Rhodiola rosea extracts and its underlying molecular mechanisms in this review article. Recent findings: In addition to its multiplex stress-protective activity, Rhodiola rosea extracts have recently demonstrated its anti-aging, anti-inflammation, immunostimulating, DNA repair and anti-cancer effects in different model systems. Molecular mechanisms of Rhodiola rosea extracts's action have been studied mainly along with one of its bioactive compounds, salidroside. Both Rhodiola rosea extracts and salidroside have contrast molecular mechanisms on cancer and normal physiological functions. For cancer, Rhodiola rosea extracts and salidroside inhibit the mTOR pathway and reduce angiogenesis through down-regulation of the expression of HIF-1α/HIF-2α. For normal physiological functions, Rhodiola rosea extracts and salidroside activate the mTOR pathway, stimulate paracrine function and promote neovascularization by inhibiting PHD3 and stabilizing HIF-1α proteins in skeletal muscles. In contrast to many natural compounds, salidroside is water-soluble and highly bioavailable via oral administration and concentrated in urine by kidney excretion. Summary: Rhodiola rosea extracts and salidroside can impose cellular and systemic benefits similar to the effect of positive lifestyle interventions to normal physiological functions and for anti-cancer. The unique pharmacological properties of Rhodiola rosea extracts or salidroside deserve further investigation for cancer chemoprevention, in particular for human urinary bladder cancer.

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