Objectives Several studies have shown that 5-aminolevulinic acid (5-ALA)-induced fluorescence cystoscopy improves the detection of superficial bladder cancer. The results have suggested a reduced ...rate of recurrent tumors with the use of 5-ALA fluorescence before bladder tumor resection. We performed a prospective, randomized trial to investigate whether the long-term tumor recurrence and residual tumor rates can be decreased using 5-ALA fluorescence diagnosis (FD). Methods A total of 301 patients with suspected superficial bladder carcinoma were randomized to transurethral resection (TUR) using conventional white light (WL) or FD. TUR was repeated to evaluate the residual tumor rate. In addition, patients were followed up for a median of 83 (WL) and 86 (FD) months to evaluate recurrence-free survival (RFS). Results Of the 301 patients, 191 were available for the efficacy analysis. The residual tumor rate was 25.2% in the WL arm versus 4.5% in the FD arm ( P <0.0001). The RFS rate after 2, 4, 6, and 8 years was 73%, 64%, 54%, and 45% in the WL group and 88%, 84%, 79%, and 71% in the FD group, respectively, revealing a statistically significant difference in favor of fluorescent TUR ( P = 0.0003). Conclusions 5-ALA-induced FD is significantly superior statistically to conventional WL TUR with respect to the residual tumor rate and RFS. This advantage of decreased bladder tumor recurrence risk was maintained with high statistical significance for at least 8 years. The differences in RFS imply that FD offers a clinically relevant procedure to reduce the incidence of tumor recurrence.
Abstract Background The prognostic value of CK20, Ki-67, and p53 has been investigated for non–muscle-invasive urothelial bladder cancers but not for the distinct and clinically challenging subset of ...pT1 bladder cancers. Objective To evaluate the prognostic value of CK20, Ki-67, and p53 within the largest series of pT1 urothelial bladder cancers. Design, setting, and participants Data from 309 patients with pT1 urothelial bladder cancer from one single urologic centre were collected. Intervention Adjuvant instillation of bacillus Calmette-Guérin was performed in each patient. A second resection was performed after 4–8 wk. A total of 76 patients underwent cystectomy. Outcome measurements and statistical analysis We conducted histomorphologic analysis; immunohistochemistry for CK20, Ki-67, and p53; and univariate and multivariate Cox regression models including recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS). Results and limitations At a median follow-up of 49 mo, we found recurrence and progression and disease-specific mortality rates of 22.7%, 20.1%, and 15.9%, respectively. CK20 expression was significantly correlated with RFS in multivariate analysis (hazard ratio HR: 5.89; 95% confidence interval CI, 1.44–24.15; p = 0.014). In multivariate analysis, Ki-67 was the only marker significantly correlated with PFS (HR: 2.80; 95% CI, 1.45–5.43, p = 0.002). Ki-67 (HR: 3.83; 95% CI, 1.59–9.26; p = 0.003), and CK20 (HR: 8.44; 95% CI,1.16–61.34; p = 0.035) were significantly correlated with CSS in multivariate analysis. The combination of CK20 and Ki-67 showed significantly worse RFS ( p = 0.026), PFS ( p = 0.003), and CSS ( p < 0.001) in tumours with a high proliferation index and abnormal CK20 expression. A retrospective study design was the major limitation of this study. Conclusions Our present analysis of the largest series of patients with pT1 urothelial bladder cancer published to date found Ki-67 and CK20 to be potential prognostic markers improving the risk stratification of pT1 bladder tumours. They are reliable indicators of biologic aggressiveness and may contribute to decision making on therapeutic strategy for pT1 bladder carcinomas.
Abstract Objectives We compared long-term outcome in patients with initial pT1G3 bladder cancer (BC) treated with early versus deferred cystectomy (CX) for recurrent pT1G3 or muscle-invasive BC after ...an initial bladder-sparing approach. The aim of this study was to compare survival rates and to analyse the influence of the recognised risk factors multifocality, tumour size, and carcinoma in situ (CIS) in initial transurethral resection of the bladder. Methods Between 1995 and 2005, a total of 105 patients were diagnosed with initial pT1G3 BC featuring ≥2 risk factors. Forty-five percent had multiple tumours, 73% tumours >3 cm in size, and 46% CIS. All patients were offered early CX. Fifty-one percent of patients opted for early and 49% underwent deferred CX for recurring BC. Risk factors were distributed evenly between the groups. Results Upstaging in the CX specimen was found in 30% of cases. No risk factor was related to upstaging. The 10-yr cancer-specific survival rate was 78% in early CX and 51% in deferred CX ( p < 0.01). No risk factor predicted cancer-related death in early CX. In survival analysis, CIS was related to a lower cancer-specific survival rate in deferred CX ( p < 0.001). Conclusions Early as opposed to deferred CX seems to prolong the cancer-specific survival rate in high-risk pT1G3 BC. Patients with CIS should be considered for early CX owing to reduced cancer-specific survival in case of deferred CX.
What's known on the subject? and What does the study add?
High‐intensity focused ultrasound (HIFU) is an alternative treatment option for localized prostate cancer (PCa), which is applied for over 15 ...years. There are conflicting recommendations for HIFU among urological societies, which can be explained by the lack of prospective controlled studies, reports on preselected patient populations and limited follow‐up providing little information on overall and cancer‐specific survival.
We report on a large, unselected consecutive patient series of patients who have undergone primary HIFU for clinically localized PCa with the longest follow‐up in current literature. Our results improve the understanding of the oncological efficacy, morbidity and side effects of primary HIFU.
Objective
To assess the safety, functional and oncological long‐term outcomes of high‐intensity focused ultrasound (HIFU) as a primary treatment option for localized prostate cancer (PCa).
Patients and Methods
We conducted a retrospective single‐centre study on 538 consecutive patients who underwent primary HIFU for clinically localized PCa between November 1997 and September 2009.
Factors assessed were: biochemical disease‐free survival (BDFS) according to Phoenix criteria (prostate‐specific antigen nadir + 2 ng/mL); metastatic‐free, overall and PCa‐specific survival; salvage treatment; side effects; potency; and continence status.
Results
The mean (sd; range) follow‐up was 8.1 (2.9; 2.1–14.0) years.
The actuarial BDFS rates at 5 and 10 years were 81 and 61%, respectively. The 5‐year BDFS rates for low‐, intermediate‐ and high‐risk patients were 88, 83 and 48%, while the 10‐year BDFS rates were 71, 63 and 32%, respectively.
Metastatic disease was reported in 0.4, 5.7 and 15.4% of low‐, intermediate‐ and high‐risk patients, respectively.
The salvage treatment rate was 18%.
Seventy‐five (13.9%) patients died. PCa‐specific death was registered in 18 (3.3%) patients (0, 3.8 and 11% in the low‐, intermediate‐ and high‐risk groups, respectively).
Side effects included bladder outlet obstruction (28.3%), Grade I, II and III stress urinary incontinence (13.8, 2.4 and 0.7%, respectively) and recto‐urethral fistula (0.7%). Preserved potency was 25.4% (in previously potent patients).
Conclusions
The study demonstrates the efficacy and safety of HIFU for localized PCa.
HIFU is a therapeutic option for patients of advanced age, in the low‐ or intermediate‐risk groups, and with a life expectancy of ∼10 years.
Abstract Objective To evaluate the long-term efficacy of high-intensity focused ultrasound (HIFU) therapy for patients with localised prostate cancer. Material and methods Patients included in this ...multicentre analysis had T1–T2 NxM0 prostate cancer, a PSA < 15 ng/ml, and a Gleason score (GS) ≤ 7, and were treated with prototypes or first-generation Ablatherm™ HIFU devices between October 1997 and August 2001. The Phoenix definition of biochemical failure was used (PSA nadir + 2). Treatment failure was defined as: biochemical failure or positive biopsy. Results A total of 140 patients with a mean (SD) age 69.1 yr (6.6) were included. Mean (SD) follow-up was 6.4 yr (1.1). Control prostate biopsies were negative in 86.4% of patients. Median PSA nadir of 0.16 ng/ml (range, 0.0–9.1) was achieved at a mean (SD) of 4.9 mo (5.2). A PSA nadir ≤ 0.5 ng/ml was recorded in 68.4% of patients. The actuarial biochemical failure–free survival rates (SR) at 5 and 7 yr were 77% and 69%, respectively. The actuarial disease–free SR at 5 and 7 yr were 66% and 59%, respectively. Conclusions This study demonstrates the effective long-term cancer control achieved with HIFU in patients with low- or intermediate-risk localised prostate cancer.
To report on our 5-year results with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. HIFU delivers high energy, causing rapid coagulation necrosis ...of tissue within the target area without damaging the surrounding tissue.
A total of 146 patients with biopsy-proven Stage T1-T2N0M0 prostate cancer have been treated using the Ablatherm device. All patients had a prostate-specific antigen (PSA) level of 15 ng/mL or less and a Gleason score of 7 or less (inclusion criteria). The mean follow-up was 22.5 months (range 4 to 62) and included PSA measurement and control sextant biopsies.
The median PSA nadir 3 months after treatment was 0.07 ng/mL (range 0 to 5.67). The median PSA level after a follow-up of 22 months was 0.15 ng/mL (range 0 to 12.11), and 87% of the patients had a constant PSA level of less than 1 ng/mL; 93.4% of all patients had negative control biopsies. One rectourethral fistula was noted after a second HIFU treatment in a patient with a history of hemicolectomy and repetitive anal fistulas. Of all the patients, 12% underwent transurethral resection after HIFU because of obstruction, but no severe stress incontinence (grade 2 to 3) was observed. Erectile function was preserved in 47.3% of patients, and the International Prostate Symptom Score and Quality of Life Index did not change from before to after treatment.
Our results demonstrated the efficacy and low-associated morbidity of HIFU. HIFU does not exclude other treatment options and is repeatable. HIFU seems to be a valid alternative treatment for patients who are not suitable for radical surgery.
MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. They play a vital role in tumorigenesis. To characterize the ...diagnostic potential of miRNAs in prostate cancer, a leading cause of cancer mortality, we performed screening of miRNA expression profiles. We used commercially available microarrays to establish miRNA expression profiles from a cohort of 20 cancer samples. The expression of selected miRNAs was analyzed by quantitative real‐time PCR and the identity of miRNA expressing cells was determined by miRNA in situ hybridization. We identified 25 miRNAs that showed a significant differential expression in cancer samples. The comparison with previously published data generated by deep sequencing of cDNA libraries of small RNA molecules revealed a concordance rate of 47% among miRNAs identified with both techniques. The differential expression of miRNAs miR‐375, miR‐143 and miR‐145 was validated by quantitative PCR. MiRNA in situ hybridization revealed that the differential expression is cancer‐cell associated. A combination of three miRNAs correctly classified tissue samples with an accuracy of 77.6% with an area under the receiver–operator characteristic curve of 0.810. Our data extend the knowledge about the deregulation of miRNAs in prostate cancer. The differential expression of several miRNAs is highly consistent using independent cohorts of tumor samples, different tissue preservation methods and different experimental methods. Our results indicate that combinations of miRNAs are promising biomarkers for the diagnosis of prostate cancer.
Prostate cancer is a leading cause of tumor mortality. To characterize the underlying molecular mechanisms, we have compared the microRNA (miRNA) profile of primary prostate cancers and noncancer ...prostate tissues using deep sequencing. MiRNAs are small noncoding RNAs of 21 to 25 nucleotides that regulate gene expression through the inhibition of protein synthesis. We find that 33 miRNAs were upregulated or downregulated >1.5-fold. The deregulation of selected miRNAs was confirmed by both Northern blotting and quantitative reverse transcription-PCR in established prostate cancer cell lines and clinical tissue samples. A computational search indicated the 3'-untranslated region (UTR) of the mRNA for myosin VI (MYO6) as a potential target for both miR-143 and miR-145, the expression of which was reduced in the tumor tissues. Upregulation of myosin VI in prostate cancer was previously shown by immunohistochemistry. The level of MYO6 mRNA was significantly induced in all primary tumor tissues compared with the nontumor tissue from the same patient. This finding was matched to the upregulation of myosin VI in established prostate cancer cell lines. In luciferase reporter analysis, we find a significant negative regulatory effect on the MYO6 3'UTR by both miR-143 and miR-145. Mutation of the potential binding sites for miR-143 and miR-145 in the MYO6 3'UTR resulted in a loss of responsiveness to the corresponding miRNA. Our data indicate that miR-143 and miR-145 are involved in the regulation of MYO6 expression and possibly in the development of prostate cancer.
Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine ...appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC.
AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test.
59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 - 44.68; p=0.025).
Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Study Type – Prognosis (systematic review) Level of Evidence 2a
What’s known on the subject? and What does the study add?
Grading so far is the most important prognostic parameter in non ...muscle‐invasive urothelial bladder cancer.
We first compared prognostic value of grading concerning WHO classifications 1973 and 2004 on stage T1 bladder cancer.
OBJECTIVE
To ascertain which of the currently defined World Health Organization (WHO) grading classifications of pT1 urothelial bladder cancer (BC), published in 1973 and 2004, is more suitable for predicting outcome.
PATIENTS AND METHODS
Transurethral resection of the bladder (TURB) specimens of 310 patients with first diagnosis of initial pT1 BC were reassessed by three urological pathologists according to the WHO classifications of 1973 and 2004. The TURB procedure was followed by either immediate cystectomy or adjuvant bacille Calmette‐Guérin (BCG) instillations. Kaplan–Meier analysis was used to compare survival rates of the different tumour grades (mean follow‐up was 57 months).
RESULTS
According to the 1973 WHO classification, none of the pT1 BC specimens were graded as G1, while 36% were graded as G2 and 64% were graded as G3. Histological reassessment according to the 2004 WHO classification highlighted only 4% low‐grade and 96% high‐grade tumours. The 10‐year cancer‐specific survival rates of high‐grade tumours (85%) were intermediate between G2 (96%) and G3 (78%).
CONCLUSIONS
The results of the present study support the presumption that the 1973 WHO classification is more suitable for predicting outcome for pT1 tumours, by defining at least two prognostic groups. A new classification should revise the definition of low‐ and high‐grade pT1 BC to preserve the prognostic value of tumour grading.
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