Quality of care in patients with bladder cancer

BACKGROUND:

Although there is level I evidence demonstrating the superiority of intravesical therapy in patients with bladder cancer, surveillance strategies are primarily founded on expert opinion. The authors examined compliance with surveillance and treatment strategies and the pursuant impact on survival in patients with high‐grade disease.

METHODS:

Using linked Surveillance, Epidemiology, and End Results (SEER)‐Medicare data, the authors identified subjects with a diagnosis of high‐grade, non–muscle‐invasive disease between 1992 and 2002 who survived 2 years and did not undergo definitive treatment during that time. Nonlinear mixed‐effects regression analyses was used to examine compliance with surveillance and treatment strategies. After adjusting for confounders using a propensity score‐weighted approach, the authors determined whether individual and comprehensive strategies during the initial 2 years after diagnosis were associated with survival after 2 years.

RESULTS:

Of 4790 subjects, only 1 received all the recommended measures. Although mean utilization for most measures significantly increased after 1997, only compliance with an induction course of bacillus Calmette‐Guerin (BCG) increased (13% to 20%; P < .001). On multivariate analysis, compliance with ≥ 4 cystoscopies, ≥ 4 cytologies, and BCG instillation was found to be lower among octogenarians and higher among those with undifferentiated, Tis, and T1 tumors, and among those individuals diagnosed after 1997. Subjects compliant with these measures had a lower hazard of mortality (hazard ratio, 0.41; 95% confidence interval, 0.18‐0.93) than those who received < 4 cystoscopies, < 4 cytologies, and no BCG.

CONCLUSION:

There was a statistically significant survival advantage found among those who received at least half of the recommended care. Improving compliance with these process‐of‐care measures via systematic quality improvement initiatives serves as the primary target to meliorate bladder cancer care. Cancer 2012;. © 2011 American Cancer Society.     

High‐risk patients with hematuria are not evaluated according to guideline recommendations

BACKGROUND:

To determine whether high‐risk patients with hematuria receive evaluation according to guideline recommendations.

METHODS:

We recently performed a screening study for bladder cancer using a urine‐based tumor marker in 1502 subjects at high risk based on aged ≥50 years, ≥10‐year smoking history, and/or a 15‐year or more environmental exposure. We evaluated use of urinalysis (UA) within 3 years preceding the screening study. Chart review was performed to determine if this subset with microhematuria received any additional evaluation.

RESULTS:

Of 1502 study participants, routine urinalysis was performed in 73.2% and 164 (14.9%) subjects had documented hematuria (>3 red blood cells / high‐power field) before inclusion. Of these, 42.1% had no further evaluation. Additional testing included repeat urinalysis (36%), urine culture (15.2%), cytology (10.4%), imaging (22.6% overall: 15.9% computed tomography, 4.3% intravenous pyelography; 2.4% magnetic resonance imaging), and cystoscopy (12.8%). Three subjects with microscopic hematuria (2%) were subsequently found to have bladder cancer during the screening study but were not referred for evaluation based on their hematuria. The source of hematuria was unknown in 65%, infection in 22%, benign prostatic enlargement in 10%, and renal stone disease in 4%, but these results are based on incomplete evaluation since only 12.8% underwent cystoscopy.

CONCLUSIONS:

Subjects at high risk for bladder cancer based on ≥10 years of smoking or environmental exposure with microscopic hematuria are rarely evaluated thoroughly and only 12.8% were referred for urologic evaluation. Further studies are needed to evaluate both the utilization and effectiveness of guidelines for hematuria. Cancer 2010. © 2010 American Cancer Society.     

Assessing the clinical benefit of nuclear matrix protein 22 in the surveillance of patients with nonmuscle-invasive bladder cancer and negative cytology: a decision-curve analysis

BACKGROUND:

Several studies have demonstrated that abnormal levels of nuclear matrix protein 22 (NMP22) are associated with bladder cancer and have led to the approval of NMP22 as a urinary biomarker by the US Food and Drug Administration. Nonetheless, the clinical significance of NMP22 remains unclear. The objective of this study was to use decision analysis to determine whether NMP22 improves medical decision‐making.

METHODS:

The current study included 2222 patients who had a history of nonmuscle‐invasive bladder cancer and current negative cytology. The authors developed models to predict cancer recurrence or progression to muscle‐invasive disease using voided NMP22 levels, cystoscopy, age, and sex. Clinical net benefit was calculated by summing the benefits (true‐positives), subtracting the harms (false‐positives), and weighting these values by the threshold probability at which a patient or clinician would opt for cytoscopy.

RESULTS:

After cystoscopy, 581 patients (26%) had cancer identified. The NMP22 level was associated significantly with bladder cancer recurrence and progression (P < .001 for both). The use of NMP22 in a model with age and sex was associated with better patient outcomes than performing cystoscopy on everyone and produced threshold probabilities > 8% for recurrence and > 3% for progression. Only offering cystoscopy to those who had a risk > 15% reduced the number of cystoscopies by 229 while missing only 25 cancer recurrences per 1000 men with negative cytology. The current study was limited by its multicenter design.

CONCLUSIONS:

For clinicians who would perform a cystoscopy at a threshold of 5% for recurrence or 1% for progression, NMP22 did not aid clinical decision‐making. For less risk‐averse clinicians who would only perform a cystoscopy at a threshold probability >thinsp;8% for recurrence or > 3% for progression, NMP22 helped to indicate which patients required cystoscopy and which could be spared this procedure. Cancer 2011. © 2011 American Cancer Society.     

Recent improvements in the detection and treatment of nonmuscle-invasive bladder cancer

In total, 70–80% of newly diagnosed bladder cancers are confined to the mucosa and staged as Ta, T1 or carcinoma in situ according to the 2002 tumor, lymph nodes and metastasis classification. The standard treatment for these nonmuscle-invasive bladder cancers is transurethral tumor resection with or without adjuvant intravesical chemotherapy or intravesical immunotherapy and subsequent follow-up. Diagnosis and follow-up of nonmuscle-invasive bladder cancer offers two main problems. First, approximately 10–20% of all tumors are not seen in standard cystoscopy. Additionally, frequently repeated follow-up cystoscopies are bothersome for the patient. As an adjunct to standard cystoscopy, fluorescence-guided cystoscopy has demonstrated significantly higher tumor detection rates and optimized patient treatment in recent Phase III studies. Second, routinely performed urine cytology is characterized by high specificity but low sensitivity. Today, several urine tests are available that may increase diagnostic accuracy and potentially prolong intervals of follow-up cystocopy. Owing to rather high recurrence rates after transurethral tumor resection in most tumors and high progression rates in poorly differentiated tumors, adjuvant intravesical chemotherapy or intravesical immunotherapy has gained widespread use in patients with nonmuscle-invasive bladder cancer. Only a few further immunomodulatory drugs, such as recombinant cytokines, have shown significant clinical effectiveness. Additional approaches, such as photodynamic therapy with different photosensitizers and thermotherapy in combination with intravesical chemotherapy, have been evaluated in Phase III studies.     

Comparison of ImmunoCyt,UroVysion, and urine cytology in detection of recurrent urothelial carcinoma

BACKGROUND:

ImmunoCyt (uCyt) and UroVysion are ancillary studies that may aid in the detection of urothelial carcinoma in urine specimens. We compared ImmunoCyt and UroVysion to urine cytology in the ability to detect recurrent urothelial carcinoma.

METHODS:

Single voided urine samples were obtained from 100 patients who had a previous history of bladder cancer. All patients underwent cystoscopy immediately after urine sample collection. Forty‐one cystoscopically suspicious lesions were biopsied. Urine samples were divided and processed blindly and independently in 3 different laboratories for ImmunoCyt, UroVysion, and urine cytology (ThinPrep method).

RESULTS:

Of the 41 cystoscopically positive cases, most cystoscopy findings showed multiple tumors that were papillary and less than 1 cm. Biopsies showed many low‐grade tumors (54%). Overall sensitivity of cytology for low‐ and high‐grade urothelial cell carcinoma was 15% and 27%, whereas ImmunoCyt was 62% and 91% and UroVysion was 8% and 18%, respectively. Overall specificity of cytology was 97%, whereas ImmunoCyt was 63% and UroVysion was 90%.

CONCLUSIONS:

ImmunoCyt is more sensitive than either cytology or UroVysion in detecting low‐grade tumors. Both cytology and UroVysion have comparable specificity in cystoscopically negative cases. Whereas ImmunoCyt may improve the cytological detection of recurrent bladder cancer, UroVysion may be used as a confirmatory test for either cytology or ImmunoCyt. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Treatment of nonmuscle invading bladder cancer: Do physicians in the United States practice evidence based medicine?

BACKGROUND:

Phase 3 clinical trials performed primarily outside the US demonstrate that intravesical instillation of chemotherapy immediately after transurethral resection of the bladder (TURB) decreases cancer recurrence rates. The authors sought to determine whether US urologists have adopted this practice, and its potential effect on costs of bladder cancer (BC) care.

METHODS:

By using 1997‐2004 MEDSTAT claims data, the authors identified patients with newly diagnosed BC who underwent cystoscopic biopsy or TURB, and those who received intravesical chemotherapy within 1 day after TURB. Economic consequences of this treatment compared with TURB alone were modeled using published efficacy estimates and Medicare reimbursements. The authors used a time horizon of 3 years and assumed that this treatment was given for all newly diagnosed low‐risk BC patients.

RESULTS:

Between 1997 and 2004, the authors identified 16,748 patients with newly diagnosed BC, of whom 14,677 underwent cystoscopic biopsy or TURB. Of these, only 49 (0.33%) received same‐day intravesical instillation of chemotherapy. From 1997 through 2004, there has been little change in the use of this treatment. The authors estimated a 3‐year savings of $538 to $690 (10% to 12%) per patient treated with TURB and immediate intravesical chemotherapy compared with TURB alone, reflecting a yearly national savings of $19.8 to $24.8 million.

CONCLUSIONS:

Instillation of intravesical chemotherapy immediately after TURB has not been embraced in the US. Adopting this policy would significantly lower the cost of BC care. Cancer 2009. © 2009 American Cancer Society.     

Recent improvements in the detection and treatment of nonmuscle-invasive bladder cancer

In total, 70-80% of newly diagnosed bladder cancers are confined to the mucosa and staged as Ta, T1 or carcinoma in situ according to the 2002 tumor, lymph nodes and metastasis classification. The standard treatment for these nonmuscle-invasive bladder cancers is transurethral tumor resection with or without adjuvant intravesical chemotherapy or intravesical immunotherapy and subsequent follow-up. Diagnosis and follow-up of nonmuscle-invasive bladder cancer offers two main problems. First, approximately 10-20% of all tumors are not seen in standard cystoscopy. Additionally, frequently repeated follow-up cystoscopies are bothersome for the patient. As an adjunct to standard cystoscopy, fluorescence-guided cystoscopy has demonstrated significantly higher tumor detection rates and optimized patient treatment in recent Phase III studies. Second, routinely performed urine cytology is characterized by high specificity but low sensitivity. Today, several urine tests are available that may increase diagnostic accuracy and potentially prolong intervals of follow-up cystocopy. Owing to rather high recurrence rates after transurethral tumor resection in most tumors and high progression rates in poorly differentiated tumors, adjuvant intravesical chemotherapy or intravesical immunotherapy has gained widespread use in patients with nonmuscle-invasive bladder cancer. Only a few further immunomodulatory drugs, such as recombinant cytokines, have shown significant clinical effectiveness. Additional approaches, such as photodynamic therapy with different photosensitizers and thermotherapy in combination with intravesical chemotherapy, have been evaluated in Phase III studies.     

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin for prophylaxis of recurrence of superficial bladder cancer: a preliminary report

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 29 patients aged a median of 70 years between January of 1991 and May of 1993. The patients received intravesical instillation of 40 mg epirubicin immediately after transurethral resection (TUR) of the bladder cancer. At 1 week after TUR, 80 mg Tokyo-strain BCG was instilled into the bladder once a week for 6 weeks. Thereafter, the patients were followed by cystoscopy and urinary cytology at 3-month intervals until recurrence was detected. Of the 29 patients, 28 had no evidence of disease over a mean follow-up period of 20 months. The 1 case of recurrence occurred at 3 months after TUR and that patient died of cancer progression. The simple recurrence rate was 3.5% after therapy. According to the person-years method, the number of recurrent tumors per 100 patient-months was 0.17. The cumulative nonrecurrence rate determined for all cases was 96.5% at 30 months. Adverse reactions, including urinary frequency, urgency, and miction pain, among others, were observed in 27 patients (93%). Only 1 patient was withdrawn from the treatment because of severe bladder-irritation symptoms due to the BCG instillation. The intravesical chemoimmunotherapy with epirubicin and BCG seemed to be effective for prophylaxis of recurrence of superficial bladder cancer.Paper presented at the 5th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 24–25 September 1993, Hakone, Japan     

Cost‐effectiveness analysis of immediate radical cystectomy versus intravesical Bacillus Calmette‐Guerin therapy for high‐risk,high‐grade (T1G3) bladder cancer

BACKGROUND:

Although both radical cystectomy and intravesical immunotherapy are initial treatment options for high‐risk, T1, grade 3 (T1G3) bladder cancer, controversy regarding the optimal strategy persists. Because bladder cancer is the most expensive malignancy to treat per patient, decisions regarding the optimal treatment strategy should consider costs.

METHODS:

A Markov Monte‐Carlo cost‐effectiveness model was created to simulate the outcomes of a cohort of patients with incident, high‐risk, T1G3 bladder cancer. Treatment options included immediate cystectomy and conservative therapy with intravesical Bacillus Calmette‐Guerin (BCG). The base case was a man aged 60 years. Parameter uncertainty was assessed with probabilistic sensitivity analyses. Scenario analyses were used to explore the 2 strategies among patients stratified by age and comorbidity.

RESULTS:

The quality‐adjusted survival with immediate cystectomy and BCG therapy was 9.46 quality‐adjusted life years (QALYs) and 9.39 QALYs, respectively. The corresponding mean per‐patient discounted lifetime costs (in 2005 Canadian dollars) were $37,600 and $42,400, respectively. At a willingness‐to‐pay threshold of $50,000 per QALY, the probability that immediate cystectomy was cost‐effective was 67%. Immediate cystectomy was the dominant (more effective and less expensive) therapy for patients aged <60 years, whereas BCG therapy was dominant for patients aged >75 years. With increasing comorbidity, BCG therapy was dominant at lower age thresholds.

CONCLUSIONS:

Compared with BCG therapy, immediate radical cystectomy for average patients with high‐risk, T1G3 bladder cancer yielded better health outcomes and lower costs. Tailoring therapy based on patient age and comorbidity may increase survival while yielding significant cost‐savings for the healthcare system. Cancer 2009. © 2009 American Cancer Society.     

立即全切与保留膀胱治疗初发T1G3膀胱癌总生存率的Meta分析(英文)

Objective:The aim of this study was to compare the therapeutic effects of bladder preserving approach transurethral resection (TURBT) with additional intravesical instillation versus immediate cystectomy in patients with newly diagnosed stage T 1 G 3 bladder cancer. Methods:Clinical data of patients with newly diagnosed T 1 G 3 bladder cancer underwent immediate cystectomy (Group A) or TURBT with additional intravesical instillation (Group B) was collected from online databases. Meta-analysis that recommended by Cochrane Collaboration was done for the data obtained. Publication bias was examined using a funnel plot. Results:Four trails, including 434 patients, were eligible for this study. The general mortality rate of group A (74/149 = 49.7%) and group B (102/285 = 35.8%) was calculated and compared in RevMan 4.2, which showed the difference on general mortality rate between the two groups was not statistical significant, with the pooled RR = 1.23 (95% CI 1.10-1.70, P > 0.05). Conclusion:Compared with TURBT, immediate cystectomy may not reduce the general mortality rate to improve the forward survival rate.     

Combined morphologic and fluorescence in situ hybridization analysis of voided urine samples for the detection and follow‐up of bladder cancer in patients with benign urine cytology

BACKGROUND.

Bladder cancer is among the 5 most common malignancies worldwide. Patients with bladder cancer are closely followed with periodic cystoscopies and urine cytology analyses due to the significant risk of tumor recurrence. The UroVysion fluorescence in situ hybridization (FISH) test demonstrated higher sensitivity over urine cytology in detecting bladder cancer by most comparative studies.

METHODS.

In the current study, the diagnostic usefulness of a combined cytology and FISH analysis approach was tested using the Duet automatic scanning system in patients with benign urine cytology who were being monitored for recurrent urothelial carcinoma or being assessed for various urologic symptoms.

RESULTS.

By combining the benefits of conventional cytology with molecular diagnostics, a more sensitive detection of bladder cancer was attained. All patients who had positive cystoscopy concomitantly with urine sampling were detected by combined analysis. Additional patients that developed transitional cell carcinoma during a follow‐up period of 24 months had a previous positive result on combined analysis. Only 2 patients with a negative combined analysis result presented with late disease recurrence (20 months and 22 months, respectively, after the negative test). Therefore, negative combined analysis was found to be predictive of a lack of disease recurrence for at least 12 months. In this timeframe, the overall sensitivity, specificity, negative predictive value (NPV), and positive predictive values of the combined analysis test were 100%, 65%, 100%, and 44%, respectively.

CONCLUSIONS.

Given the absolute sensitivity and NPV of the combined analysis test, the management of patients with a negative combined analysis result might be revised and allow for more flexible assessment and management of bladder cancer patients relying more on urine bound tests. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.     

Prevention of Recurrence of Superficial Bladder Cancers: Intravesical Instillation of Bacillus Calmette-guerin versus Bacillus Calmette-guerin plus Epirubicin

Purpose The short-term effects of intravesical chemoimmunotherapy with epirubicin and Bacillus Calmette- ‍Guerin (BCG) administered repeatedlly for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were ‍investigated in 22 patients with a median of 70 years between March, 1995 and February, 1999, and were compared ‍with those of BCG monotherapy in 50 patients between March, 1995 and February, 1999. ‍Patients and Methods The patients underwent intravesical instillation of Tokyo-strain BCG with or without ‍epirubicin after transurethral resection (TUR) of bladder cancer. For the combined treatment, at 1❛2 weeks after ‍TUR, epirubicin (40 mg) and BCG (80 mg) were instilled into the bladder by turn once a week for 12 weeks. For the ‍BCG alone group, 80 mg instillation were performed with the same schedule. Thereafter, the patients were followed ‍by cystoscopy and urinary cytology every 3 months for up to 3 years after intravesical therapy. ‍Results and Conclusions The simple recurrence rate was 22.7% (5/21) in patients with chemoimmunotherapy ‍and 32.0% (16/50) in BCG-treated patients. Adverse reactions, including increased frequency of urination, urgency ‍and miction pain, were observed in 18 patients (85.7%) undergoing chemoimmunotherapy and 58.0% undergoing ‍BCG monotherapy. One patient receiving chemoimmunotherapy was withdrawn from treatment because of severe ‍bladder-irritation symptoms due to instillation. Intravesical chemoimmunotherapy using epirubicin and BCG was ‍inferior in comparison with BCG monotherapy for prophylaxis of recurrence of superficial bladder cancer.     

Racial differences in treatment and outcomes among patients with early stage bladder cancer

BACKGROUND:

Black patients are at greater of risk of death from bladder cancer than white patients. Potential explanations for this disparity include a more aggressive phenotype and delays in diagnosis resulting in higher stage disease. Alternatively, black patients may receive a lower quality of care, which may explain this difference.

METHODS:

Using Surveillance, Epidemiology, and End Results (SEER)‐Medicare data for the years from 1992 through 2002, the authors identified patients with early stage bladder cancer. Multivariate models were fitted to measure relations between race and mortality, adjusting for differences in patients and treatment intensity. Next, shared‐frailty proportional hazards models were fitted to evaluate whether the disparity was explained by differences in the quality of care provided.

RESULTS:

Compared with white patients (n = 14,271), black patients (n = 342) were more likely to undergo restaging resection (12% vs 6.5%; P < .01) and urine cytologic evaluation (36.8% vs 29.7%; P < .01), yet they received fewer endoscopic evaluations (4 vs 5; P < .01). The use of aggressive therapies (cystectomy, systemic chemotherapy, radiation) was found to be similar among black patients and white patients (12% vs 10.2%, respectively; P = .31). Although black patients had a greater risk of death compared with white patients (hazards ratio [HR], 1.23; 95% confidence interval [95% CI], 1.07‐1.42), this risk was attenuated only modestly after adjusting for differences in treatment intensity and provider effects (HR, 1.22; 95% CI, 1.06‐1.42).

CONCLUSIONS:

Although differences in initial treatment were evident, they did not appear to be systematic and had unclear clinical significance. Whereas black patients are at greater risk of death, this disparity did not appear to be caused by differences in the intensity or quality of care provided. Cancer 2010. © 2010 American Cancer Society.     

Clinical evaluation of two consecutive UroVysion fluorescence in situ hybridization tests to detect intravesical recurrence of bladder cancer: a prospective blinded comparative study in Japan

Background

We evaluated the use of UroVysion fluorescence in situ hybridization tests to detect the intravesical recurrence of bladder cancer during follow-up after a transurethral resection of bladder tumor (TURBT).

Methods

In this prospective, blinded, comparative study, 486 patients treated by TURBT within the prior 2 years were registered at 12 centers. Urine cytology and UroVysion tests were performed once or twice at a central testing laboratory. For the patients with no suspicious findings of bladder cancer in the first analysis, the same examination set was repeated 3 months later as the second analysis. Totals of 468 and 399 patients were eligible for the first and second analyses, respectively. We determined the sensitivity and specificity of two consecutive UroVysion tests.

Results

Bladder cancers were identified in 44 patients at the first analysis. The UroVysion test had 50.0% (95% CI 35.2–64.8%) sensitivity and 72.4% (68.3–76.8%). Urine cytology had 4.5% (0.0–10.7%) sensitivity and 99.8% (99.3–100.0%) specificity. The concordant rate of the first and second UroVysion test results was 72% (kappa coefficient 0.157). Interestingly, the patients with two consecutive positive UroVysion test results had the highest cancer detection rate (14.8%), which is greater than those of the patients with a positive result in either (7.2%) or neither (1.2%) of the two tests at the 3-month follow-up.

Conclusions

The UroVysion test provided higher sensitivity than urine cytology to detect bladder cancer during post-TURBT follow-up. Two consecutive UroVysion tests might be a better indicator to predict intravesical recurrence.

     

Impact of evidence-based clinical guidelines on the adoption of postmastectomy radiation in older women

BACKGROUND:

Although postmastectomy radiation therapy (PMRT) improves survival for patients with high‐risk breast cancer, previous literature suggested that it is underused. The impact of recent clinical guidelines on PMRT use is unknown. Accordingly, the authors used the Surveillance, Epidemiology, and End Results (SEER)‐Medicare cohort to determine whether the use of PMRT has increased in response to evidence‐based guidelines.

METHODS:

In total, 38,322 women aged ≥66 years who underwent mastectomy for invasive breast cancer between 1992 and 2005 were identified. Time trends in the receipt of PMRT for low‐risk (T1/T2 N0), intermediate‐risk (T1/T2 N1), and high‐risk (T3/T4 and/or N2/N3) patients were characterized. Multivariate logistic regression identified risk factors for PMRT omission.

RESULTS:

The receipt of PMRT by patients with high‐risk breast cancer increased from 36.5% (95% confidence interval, 26%‐46.9%) to 57.7% (95% confidence interval, 46.9%‐68.4%) between 1996 and 1998 with the publication of landmark clinical trials. However no further increase in PMRT use was observed between 1999 and 2005 despite publication of multiple guidelines endorsing its use; during this period, only 54.8% (2729 of 4978) of high‐risk patients received PMRT. Within this high‐risk group, patients with smaller tumors or less advanced lymph node disease were at risk for PMRT omission.

CONCLUSIONS:

After an initial increase in PMRT use in response to clinical trials, the use of PMRT did not increase further in response to guideline publication, and nearly 50% of patients with high‐risk breast cancer still do not receive PMRT. Additional research is needed to determine how clinical guidelines can be used to bridge the gap between level I evidence and clinical practice. Cancer 2011;. © 2011 American Cancer Society     

Effect of internal iliac artery chemotherapy after transurethral resection of bladder tumor for muscle invasive bladder cancer

Objective： To evaluate the clinical effect of transurethral resection of bladder tumor（TUR-BT） combined with internal iliac artery chemotherapy and intravesical instillation therapy for muscle invasive bladder cancer（MIBC）.
Methods： From February 2007 to April 2014, 62 patients with MIBC were treated with TUR-BT combined with intravesical instillation therapy, with or without internal iliac artery chemotherapy, and the chemotherapy regimen is gemcitabine and cisplatin（GC）. The bladder preservation and survival rate as well as cancer-specific survival（CSS） rate and overall survival（OS） rate of the two groups were compared.
Results： Sixty-two patients were followed-up for 26-102 months with an average of 58.4±3.1 months. Recurrence-free survival（RFS） at 2-year for TUR ＋ GC group and TUR group were 77.8% and 53.8%, respectively. Bladder preserved rate（BPR） at 3-year for TUR ＋ GC group and TUR group were 94.4% and 80.8%. CSS rate at 2-year for TUR ＋ GC group and TUR group were 94.4% and 84.6%. The diseasefree survival（DFS） at 1-year for TUR ＋ GC group and TUR group were 83.3% and 61.5%, and 77.8% and 53.8% for the 2nd year. OS at 2-year for TUR ＋ GC group and TUR group were 88.9% and 92.3%.
Conclusions： TUR-BT and intravesical instillation therapy combined with internal iliac artery chemotherapy for MIBC had a better outcome at RFS, BPR and DFS than the treatment without internal iliac artery chemotherapy, and no difference in OS and CSS.     

A multiplexed,particle‐based flow cytometric assay identified plasma matrix metalloproteinase‐7 to be associated with cancer‐related death among patients with bladder cancer

BACKGROUND:

The current study was conducted to demonstrate the utility of a multiplexed, particle‐based flow cytometric assay for the simultaneous analysis of a panel of matrix metalloproteinases (MMPs) using small volumes of plasma samples from patients with bladder cancer. In addition, the authors attempted to test the hypothesis that plasma levels of MMPs are associated with time to cancer‐related death.

METHODS:

Plasma MMP concentrations (MMP‐1, ‐2, ‐3, ‐7, ‐8, ‐9, and ‐12) in 135 patients presenting with high‐grade ≥T1 bladder cancer were measured. Data regarding clinical and pathologic features was ascertained in a retrospective fashion.

RESULTS:

The median duration of follow‐up was 30.4 months. At the time of analysis, 61 patients had died, including 45 (33.3%) who died of bladder cancer. Plasma MMP‐12 was not measurable. For all other MMPs, the intra‐assay coefficient of variation varied from 6.12% to 9.82%. MMP‐1, ‐2, ‐3, ‐8, and ‐9 were not found to be significantly associated with time to cancer‐related death. Plasma MMP‐7 levels were significantly associated with time to cancer‐related death after adjustment for competing clinical and pathologic features (hazard ratio [HR], 2.2; 95% confidence interval [95% CI], 1.1‐4.5 [P = .022]). The 5‐year median cancer‐specific survival rates for those patients with MMP‐7 levels above and below the median value (300 pg/mL) were 73.6% (95% CI, 60.0‐83.2%) and 48.0% (95% CI, 32.5‐61.9%), respectively (P = .01).

CONCLUSIONS:

Multiplexed, particle‐based flow cytometric assay allows for the high‐throughput measurement of multiple plasma or serum proteins simultaneously. By using this new technology in a cohort of patients with bladder cancer, plasma levels of MMP‐7 were identified as being significantly associated with time to cancer‐related death Cancer 2010. © 2010 American Cancer Society.     

Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study

Intravesical gemcitabine (Gem) has shown promising activity against transitional cell carcinomas (TCC) of the bladder, with moderate urinary toxicity and low systemic absorption. The present phase II study evaluated the activity of biweekly intravesical treatment with Gem using a scheme directly derived from in vitro preclinical studies. Patients with Bacille Calmette-Guérin (BCG) -refractory Ta G3, T1 G1-3 TCC underwent transurethral bladder resection and then intravesical instillation with 2000 mg Gem diluted in 50 ml saline solution on days 1 and 3 for 6 consecutive weeks. Thirty-eight (95%) of the 40 patients showed persistent negative post-treatment cystoscopy and cytology 6 months after Gem treatment, while the remaining 2 patients relapsed at 5 and 6 months. At a median follow-up of 28 months, recurrences had occurred in 14 patients. Among these, four had downstaged (T) disease, three had a lower grade (G) lesion and three had a reduction in both T and G. Urinary and systemic toxicity was very low, with no alterations in biochemical profiles. In conclusion, biweekly instillation of Gem proved active in BCG-refractory Ta G3, T1 G1-3 TCC. Our results highlight the importance of preclinical studies using in vitro systems that adequately reproduce the conditions of intravesical clinical treatment to define the best therapeutic schedule.     

Lactobacillus rhamnosus GG induces tumor regression in mice bearing orthotopic bladder tumors

(Cancer Sci 2010; 101: 751–758) The present gold standard for bladder cancer is Mycobacterium bovis, Bacillus Calmette Guerin (BCG) immunotherapy. But it has a non‐responder rate of 30–50% and side effects are common. Lactobacillus casei strain Shirota has been reported to reduce the incidence of recurrence in bladder cancer patients and to cure tumor‐bearing mice. Our aim was to determine if Lactobacillus rhamnosus GG (LGG) could be as efficacious as BCG in a murine model of bladder cancer. MB49 bladder cancer cells secreting human prostate‐specific antigen were implanted orthotopically in female C57BL/6 mice and urinary prostate‐specific antigen levels were used as a marker of tumor growth. Mice were treated with either live or lyophilized LGG given via intravesical instillation, or both oral and intravesical LGG given once a week for a period of 6 weeks starting at day 4 after tumor implantation. A comparison of LGG and BCG immunotherapy was also carried out. LGG therapy (live or lyophilized) significantly (P = 0.006) increased the number of cured mice. Cytokine arrays and immune cell recruitment analysis revealed differences between untreated, treated, cured, and tumor‐bearing mice. LGG therapy restored XCL1 levels to those in healthy bladders. LGG also recruited large numbers of neutrophils and macrophages to the tumor site. Intravesical LGG and BCG immunotherapy had cure rates of 89 and 77%, respectively, compared with 20% in untreated mice. LGG has the potential to replace BCG immunotherapy for the treatment of bladder cancer.     

Comparison between intravesical and oral administration of 5-aminolevulinic acid in the clinical benefit of photodynamic diagnosis for nonmuscle invasive bladder cancer

BACKGROUND:

This study was undertaken to evaluate the clinical value of photodynamic diagnosis (PDD) with intravesical and oral instillation of 5‐aminolevulinic acid (ALA) (ALA‐PDD), and transurethral resection of bladder tumor (TURBT) guided by ALA‐PDD (PDD‐TURBT) for nonmuscle invasive bladder cancer.

METHODS:

Of all 210 cases, 75 underwent PDD with intravesically applied ALA, and 135 cases underwent PDD with orally applied ALA. Diagnostic accuracy was evaluated by comparing the level on images of ALA‐induced fluorescence with the pathological result. PDD‐TURBT was performed in 99 completely resectable cases corresponding to 210 ALA‐PDD cases. To evaluate the abilities of PDD‐TURBT, survival analysis regarding intravesical recurrence was retrospectively compared with the historical control cases that underwent conventional TURBT.

RESULTS:

The diagnostic accuracy and capability of ALA‐PDD were significantly superior to those of conventional endoscopic examination. Moreover, 72.1% of flat lesions, including dysplasia and carcinoma in situ, could be detected only by ALA‐PDD. The recurrence‐free survival rate in the cases that underwent PDD‐TURBT was significantly higher than that of conventional TURBT. Moreover, multivariate analysis revealed that the only independent factor contributing to improving prognosis was PDD‐TURBT (hazard ratio, 0.578; P = .012). Regardless of the ALA administration route, there was no significant difference in diagnostic accuracy, ability of PDD, or recurrence‐free survival. All procedures were well tolerated by all patients without any severe adverse events.

CONCLUSIONS:

This multicenter study is likely to be biased, because it is limited by the retrospective analysis. This study suggests that regardless of the ALA administration route, ALA‐PDD and PDD‐TURBT are remarkably helpful in detection and intraoperative navigation programs. Cancer 2012;. © 2011 American Cancer Society.