To Transurethral Resection Research Articles

Long-term Follow-up and Factors Associated with Active Surveillance Failure for Patients with Non–muscle-invasive Bladder Cancer: The Bladder Cancer Italian Active Surveillance (BIAS) Experience

Active surveillance (AS) has been proposed as an alternative to transurethral resection (TUR) in selected patients with recurrent low-risk non–muscle-invasive bladder cancer (NMIBC). Here we report long-term results for patients on AS and investigate features associated with AS failure. Cases with recurrence after diagnosis of low-grade (LG) pTa/pT1a NMIBC were enrolled in the Bladder Italian Active Surveillance (BIAS) project. Over 251 AS events, we observed 130 failures (51.8%). In these patients, final pathology showed 25 benign lesions (19.2%) and 92 LG Ta (70.7%), 12 high-grade Ta/T1 (9.2%), and one T2 (0.7%) tumor. The treatment-free probability at 12, 18, 24, and 36 mo was 59.7%, 54.5%, 46.3%, and 40.4%, respectively. We identified 95 patients (37.8%) who remained on AS for >18 mo. A multivariable Cox regression model confirmed that patients with a history of multiple TURs (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.01–2.51) and those with more than one lesion at AS entry (HR 1.63, 95% CI 1.05–2.54) were significantly more likely to experience AS failure. Our results confirm that well-selected patients with NMIBC can safely remain on AS for a long period of time. Multiple TURs and multiple lesions at AS enrollment are associated with a higher risk of AS failure. Patient summaryActive surveillance has been proposed as an alternative to surgery for patients with recurrent low-risk superficial bladder cancer. Our report confirms that well-selected patients can safely avoid or postpone surgery.

Radical cystectomy for pT1 urothelial carcinoma of bladder not amenable to TURBT: Long-term results

PurposeThis study sought to identify factors associated with survival of pT1 urothelial carcinoma of bladder (UCB) after radical cystectomy (RC). MethodsThis study consists of 114 pT1 UCB [primary 83, recurrent 31, none were amenable to transurethral resection (TUR)] treated by radical cystectomy. Survival analysis using Cox regression tests were performed to identify factors associated with survival of pT1 UCB after RC. ResultsPelvic lymph node (LN) status, age and lymphovascular invasion (LVI) are associated with survival of pT1 UCB after RC; recurrent pT1 UCB of high grade origin (HGO) tends to have poorer CSS than primary pT1 UCB or recurrent pT1 UCB of low grade origin (LGO) (5-year and 10-year CSS rates was 75% and 73% for primary cases; 77% and 77% for recurrent pT1 UCB of LGO; and 56% and 37% for recurrent pT1 UCB of HGO, p = 0.078). ConclusionsLN status, age and LVI were significantly associated with survival of pT1 UCB after RC. Recurrent pT1 UCB of HGO should be managed with radical cystectomy in a timely fashion given that these cases tend to have poorer CSS than primary pT1 UCB after RC, even if they did not progress to muscle-invasive bladder cancer (MIBC).

Diffusion‐weighted magnetic resonance imaging in follow‐up of superficial urinary bladder carcinoma after transurethral resection: initial experience

What's known on the subject? and What does the study add? Diffusion-weighted (DW) MRI is a non-invasive technique measuring the microscopic mobility of water molecules in the tissues without contrast administration. It provides information on perfusion and diffusion simultaneously in any organ, so it can be used to differentiate normal and abnormal tissue structure, and it might help in the characterization of various abnormalities. In recent years, DW-MRI has been applied in the evaluation of urinary tract lesions, such as malignant renal, prostatic and bladder tumours; however, it has not previously been tested on its ability to distinguish residual cancer from fibrotic and inflammatory changes secondary to transurethral resection (TUR) and intravesical chemotherapy, both of which manifest as bladder-wall thickening on T2-weighted MRI. This is the first study to show the feasibility of DW-MRI in follow-up of patients with superficial bladder tumours after TUR. DW-MRI was highly reliable in differentiating post-TUR inflammatory changes from bladder tumours, with results similar to those of conventional cystoscopy. This non-invasive method could be used efficiently in future for follow-up of this patient group and may obviate the need for routine cystoscopy. • To study the feasibility of using diffusion-weighted (DW) magnetic resonance imaging (MRI) in bladder cancer follow-up after transurethral resection (TUR). • Included in the study were 47 patients with a history of TUR of superficial bladder carcinoma, who were admitted to our centre between January and December 2011 for follow-up cystoscopy. • Before cystoscopy, DW-MRI was performed and the apparent diffusion coefficient (ADC) value was measured in a circular region of interest within the carcinoma and normal bladder wall. • Two radiologists, blinded to the results of cystoscopy, independently interpreted the DW images. • A comparison of imaging findings with those of cystoscopy was performed using the McNemar test. • In our 47 patients, cystoscopy identified 34 bladder lesions in 24 patients and in the remaining 23 the bladder looked normal. • In the 24 patients with malignant bladders, DW-MRI detected 32/34 tumours with two false-negative findings of lesions in two patients. • In 23 patients with non-malignant bladders, the DW-MRI data were accurate for 21 patients, as two patients were misdiagnosed as malignant. • The sensitivity, specificity, accuracy, positive and negative predictive values of DW-MRI for identifying bladder tumours were 91.6% (22/24), 91.3% (21/23), 91.5% (43/47), 91.6 (22/24) and 91.3 (21/23), respectively. • Using the McNemar test there was no significant difference between DW-MRI and cystoscopy. • DW-MRI has a high reliability in differentiating post-TUR inflammatory changes from bladder tumours, which is similar to that of cystoscopy. • DW-MRI could be a first-line diagnostic test in follow-up of patients after TUR.

Neoadjuvant Short-term Intensive Intravesical Mitomycin C Regimen Compared with Weekly Schedule for Low-grade Recurrent Non–muscle-invasive Bladder Cancer: Preliminary Results of a Randomised Phase 2 Study

BackgroundThe schedule for intravesical chemotherapy administration has not been definitively established in patients with low-grade recurrent non–muscle-invasive bladder cancer (NMIBC). ObjectiveTo assess both the feasibility and the efficacy of a short-term intensive schedule of neoadjuvant intravesical chemotherapy in patients with recurrent NMIBC. Design, setting, and participantsA randomised phase 2 clinical study included 54 patients with recurrent NMIBC who were submitted to neoadjuvant chemotherapy intravesical instillations according to two different timing schedules. The study was performed at a tertiary care referral centre. InterventionIntravesical mitomycin C (MMC) 40mg/40ml was administered according to a schedule of either one instillation per week for 6 wk (group 1) or three instillations per week for 2 wk (group 2) prior to transurethral resection (TUR). Outcome measurements and statistical analysisLocal and systemic toxicity were investigated using the US National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 questionnaire at each instillation and the SF-36 questionnaire at randomisation and before TUR. A video-recorded cystoscopy and TUR were performed within 14 d after treatment completion. Results and limitationsGroups 1 and 2 each were assigned 27 cases. Two patients (7.4%) in group 2 could not complete the scheduled treatment because of severe lower urinary tract symptoms. No statistically significant difference in SF-36 domain score was documented pre- and post-treatment between groups. Likewise, no statistically significant difference in treatment-related toxicity according to the CTCAE v.4 questionnaire was registered. Twelve patients (44.4%) in group 1 and 19 patients (70.4%) in group 2 (p=0.04) had complete tumour response. The small number of patients included represents the main limitation of the study. ConclusionsThe intensive short-term schedule of neoadjuvant chemotherapy is safe and without additional toxicity compared with the weekly regimen. The increased ablative effect may be explained by the improved adherence of the scheduled timing to the duplication rate of tumour cells.

Update on Intravesical Agents for Non-Muscle-Invasive Bladder Cancer

Major controversies still exist with regard to the indication, type and regimen of intravesical therapy for non-muscle-invasive bladder cancer. Other areas of controversy are the criteria for response/failure of treatment and for decisions regarding secondary intravesical therapy versus radical cystectomy. In this article, we analyze the different intravesical therapeutic strategies and compare their safety and efficacy. Well-designed clinical trials have found that the addition of bacillus Calmette-Guerin (BCG) to transurethral resection (TUR) decreases the risk for both disease recurrence and progression. These encouraging results are sustained even in patients with recurrent or aggressive disease, including patients whose prior intravesical chemotherapy has failed. Most investigators believe that the efficacy of BCG therapy can be maximized with maintenance therapy. Mitomycin C (MMC), the most commonly used intravesical chemotherapy to date, decreases the risk of disease recurrence but not disease progression when used after TUR compared with TUR alone. The oncologic efficacy of intravesical MMC can be optimized by increasing its concentration in addition to alkalinizing and reducing urine production. For patients at high risk of disease progression, BCG with maintenance therapy should be the preferred primary intravesical therapeutic strategy. However, MMC can be considered as a viable alternative for patients with papillary tumors (no carcinoma in situ) that are at low or intermediate risk of disease progression. Combination intravesical therapy may be more successful than single-agent strategies. Intravesical therapy failures indicate the need to include radical cystectomy as an option in the management decision.

Intravesical Instillation Treatment of Non–muscle-invasive Bladder Cancer

Abstract Bacillus Calmette-Guerin (BCG) is a proven and valuable adjunct to transurethral resection (TUR) for decreasing recurrence and progression of non–muscle-invasive bladder cancer (NMIBC). The European Association of Urology (EAU) and American Urological Association (AUA) have similar recommendations for induction and maintenance treatment in patients based on clinical and pathologic risk factors. To most effectively treat this disease, clinicians must be aware of the risk factors for treatment failure, strategies to deal with failures and BCG intolerance, and the appropriate threshold to proceed with radical cystectomy (RC). Combination, alternative, and multimodal intravesical treatments for patients with BCG failure have arisen in recent years, and the outcomes data are reviewed here.

Detection of survivin mRNA in urine of patients with superficial urothelial cell carcinomas

The aim of the present study was to assess if the presence of survivin mRNA in exfoliated cells present in urine samples can be a reliable marker of the presence of bladder tumour and recurrence. Urine samples from 30 patients with superficial urothelial cell carcinomas (UCC) were collected prior to transurethral resection (TUR) of the tumour and in the first routine follow-up, three months after TUR. Detection of survivin mRNA was performed by reverse transcription-polymerase chain reaction (RT-PCR). No correlation was observed between survivin detection and the clinicopathological variables analysed, nevertheless, when patients were grouped into low-grade (G1) and high-grade (G2+G3) tumours, statistically significant differences were found between both groups (p=0.04). When we analysed the results of survivin detection and urinary cytology together, we observed that informative cases rose from 27.8% to 44.4%. Also, Kaplan-Meier curves for patients with negative cytology in the first followup, categorised according to survivin detection, revealed that survivin mRNA positive cases recurred earlier than negative ones. From our results we can conclude that detection of survivin expression can be a reliable tumour marker, but more studies are needed to clarify the potential of survivin to predict recurrences. These results showed that survivin detection in combination with conventional urinary cytology can be a useful tool to increase the sensitivity in detecting the presence of a recurrence after TUR.

Clinically Relevant Reduction in Risk of Recurrence of Superficial Bladder Cancer Using 5-Aminolevulinic Acid-Induced Fluorescence Diagnosis: 8-Year Results of Prospective Randomized Study

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). 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). 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). 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.

Can fine needle aspiration biopsy detect incidental prostatic carcinoma (T1) prior to TUR?

The purpose of this study was to find out whether randomly taken fine needle aspiration biopsy (FNA) can detect incidental prostatic carcinoma prior to transurethral resection (TUR) and what are the effects of local tumor stage and grade on detection rate. Biopsies were taken from 344 patients, who came to hospitals for elective TUR without clinical evidence of prostatic carcinoma. Histologic examination of the TUR material showed prostatic carcinoma in 49 cases (14%). Sufficient material for cytologic examination was found in 343 cases. Of the 16 cases of T1a carcinoma in histologic examination, cytology found only 1, which was a G3 carcinoma. Of 33 T1b carcinoma in histologic examination, cytology found 6 and an additional 7 were suspect findings. Out of 6 G3 tumors in histologic examination, cytology showed 4. In our hands the proportion of false-negative cytologic findings in randomly taken FNA was so large that routine use of random FNA prior to TUR or as a screening procedure cannot be recommended, but positive FNA finding can be regarded as cancer.

Transurethral-resection zone prostate cancer detected at cystoprostatectomy. A detailed histologic analysis and clinical implications

The authors identified incidental adenocarcinoma of the prostate in serial cross-sections of prostates from 61 of 100 patients having cystoprostatectomy for bladder cancer. In 20 patients, cancer foci were in the prostatic region accessible to transurethral resection (TUR). Eight of these 20 patients had stage A1 disease (less than or equal to 3 foci); in six of these patients all foci were located at or within the transition-zone boundary only. Twelve patients had stage A2 disease (greater than 3 foci); in none were more than three foci at or within the transition-zone boundary. Among the 20 patients, 84 tumor foci were distributed as follows: 62% in the peripheral zone, 10% in the transition zone, 3% in the central zone, and 25% in the transition zone boundary. The authors' data suggest that Stage A prostate cancer, like larger clinically detectable cancers, is multifocal, multizonal, and similarly distributed with respect to the urethra. No case of Stage A1 disease would have been reclassified as Stage A2 by repeat TUR of the entire transition zone and transition zone boundary. The authors' results confirm those of previous studies that report a high incidence of residual carcinoma in regions not accessible to TUR in patients with presumptive Stage A1 disease and suggest that ultrasonography and ultrasonographically guided biopsies, rather than repeat TUR, may more accurately define the extent of Stage A disease in some patients.

Septicemia after transurethral prostatectomy

Septicemia occurred in 18 of 1,604 patients subjected to transurethral resection (TUR) of the prostate. Six patients died postoperatively, 4 of septicemia. In 11 patients septicemia was provoked by TUR in the presence of urinary infection and in the absence of appropriate antibiotic cover. Septicemia was provoked by catheter removal in 2 similarly infected patients. In the remaining 5 patients the urine was sterile at operation but became infected prior to catheter removal, and this maneuver precipitated septicemia.