Non-muscle Invasive Transitional Cell Carcinoma Research Articles

Long term outcomes and impact on renal function following radical cystectomy.

To assess clinical, oncological outcomes and impact on renal function in patients who underwent the radical cystectomy with pelvic lymphadenectomy for muscle invasive and high risk non-muscle invasive transitional cell carcinoma of urinary bladder without evidence of non-regional lymph nodes and distant metastasis. With curative intent total 156 patients underwent radical cystectomy with pelvic lymphadenectomy from January 2015 to December 2022. Total 132/156 patients had primary transitional cell carcinoma of bladder. Thirty patients, presented with obstructive nephropathy, operated after stabilization of renal function. Pre-operatively and post-operatively eGFR calculated using modified diet in renal disease formula. In present study 114 (86.36%) patients had high grade TCC, 70 (53.02%) patients had organ confined disease. Nodal extension seen in 74 (56.06%) patients. Perioperative mortality noted in 36 (27.2%) patients. The overall survival and recurrence free survival (RFS) over 5 years was 66.67 and 45.45%. RFS was significantly related to pathological stage, nodal status, histological-grade, positivity of surgical margin and time of surgery from diagnosis. Total 92/132 (69.7%) patients had recurrence. Pelvic recurrence in 10/92 (10.87%) whereas 82/92 (89.13%) patients had distant recurrence. Pre-operatively mean creatinine was 2.6 mg/dl and mean eGFR was 38.9 ml/h in patients who presented with obstructive nephropathy after stabilization of renal function. Post-operatively in 46/132 (34.8%) patients had improvement in eGFR while 86/132 (65.2%) patients had deterioration of eGFR over 62 months of median follow up. Radical cystectomy provides good overall survival outcomes. Pre-operative eGFR has significant impact on post-operative renal function in long term.

Novel uses of complement inhibitors in myasthenia gravis-Two case reports.

Myasthenia gravis (MG) is a rare, life-threatening immune-related adverse effect (irAE) of immune checkpoint inhibitor (ICI) treatment. C5-complement inhibitors are effective treatments for acetylcholine receptor antibody (AChR ab) positive generalized MG. We describe the use of eculizumab/ravulizumab in two patients with MGreceiving concomitant pembrolizumab. This was a retrospective review of two medical records. Patient 1: An 80-year-old male with recurrent, non-muscle invasive transitional cell carcinoma of the bladder developed ICI-induced AChR ab positive MG (ICI-MG), myositis, and myocarditis 2 weeks after the first dose of pembrolizumab. Myositis responded to corticosteroids. MG responded to eculizumab, followed by ravulizumab. He died of metastatic cancer 8 months later. Patient 2: A 58-year-old male had refractory thymoma-associated AChR ab-positive MG, which responded to eculizumab. He developed metastatic Merkel cell cancer necessitating pembrolizumab. MG remained stable on eculizumab. He had no irAEs for 22 months, with positron emission tomographic resolution of cancer. He then developed mild, indolent retinal vasculitis, which responded to prednisone. Discontinuation of pembrolizumab for 5 months resulted in cancer recurrence; pembrolizumab was resumed with peri-infusion pulse prednisone. MG remained stable and he continues eculizumab. In the first patient, eculizumab, followed by ravulizumab, improved ICI-MG. In the second patient, eculizumab treatment may have had a prophylactic effect on the development of ICI-induced irAEs. The effect of complement inhibition on cancer outcomes of ICI therapy is unknown. A possible biologic basis for complement inhibitors in reducing irAEs of ICI, especially in the presence of underlying autoimmune disease, merits evaluation.

Metastatic non-muscle invasive transitional cell carcinoma of urinary bladder: a case report

BackgroundAxillary lymphadenopathy is a common clinical presentation of variety of benign and malignant diseases. However, majority of patients with unilateral axillary lymph node enlargement have an underlying malignancy in which association with breast carcinoma being the commonest one. In most of these patients there will be a discernible primary tumor, either clinically or radiologically. However, in axillary lymphadenopathy with negative mammogram is not very common, and in this case other malignant causes should also be considered in addition to occult breast cancer and these can be metastases from other primary tumors for, e.g., lung, genitourinary tract, gastrointestinal, ovarian, thyroid carcinomas and malignant melanoma.Axillary node is an uncommon site of metastases from Transitional cell carcinoma (TCC) of urinary bladder even from its muscle invasive form, and distant metastasis from low grade superficial tumors without muscle invasion or regional metastasis is a very rare occurrence. Here we present a case of axillary nodal metastases from non-muscle invasive (superficial) bladder cancer without history of local recurrence and regional metastases.Case presentationWe present a case of female patient who complaint of hard swelling in right axilla and right breast enlargement. Patient had past history of non-muscle invasive transitional cell carcinoma of urinary bladder (pTa, grade II A) which had been treated accordingly. No recurrence of bladder growth had been observed on serial check cystoscopies. On clinical examination of breast and axilla, right breast appears enlarged and there were palpable hard fixed axillary lymph nodes. Ultrasound showed enlarged malignant looking lymph nodes. Occult breast carcinoma with metastatic axillary lymph nodes was our initial impression; however, subsequent biopsy of axillary lymph nodes showed Transitional cell carcinoma.ConclusionsThis patient’s case emphasizes the importance of having sound knowledge of natural behavior of primary tumor and common and uncommon sites of distant metastases. The causes of unilateral axillary lymphadenopathy include both benign and malignant disease.

A phase 3 study of the subcutaneous programmed cell death protein 1 inhibitor sasanlimab as single agent for patients with bacillus Calmette-Guérin, unresponsiv,e high-risk, non-muscle invasive bladder cancer: CREST Study Cohort B.

TPS4614 Background: Bacillus Calmette-Guérin (BCG) therapy is the standard of care for high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor. However, disease recurrence or progression is common and patients with BCG-unresponsive disease are unlikely to respond to further BCG therapy. In these patients, the current standard of care is radical cystectomy and bladder-preserving treatment options, limited to intravesical chemotherapy or intravenous pembrolizumab. In a phase 1 study, sasanlimab (PF-06801591), a monoclonal antibody to programmed cell death protein 1 (PD-1), was administered subcutaneously at 300 mg every 4 weeks. Sasanlimab had an acceptable safety profile and showed clinical activity aligned to other anti-PD-1/PD-ligand 1 (PD-L1) agents in patients with advanced urothelial carcinoma and non-small cell lung cancer, while offering the convenience of subcutaneous administration. Therefore, CREST Study Cohort B aims to evaluate sasanlimab administered subcutaneously in patients with BCG-unresponsive NMIBC. Methods: CREST Study Cohort B is a non-randomized, multicenter, multinational, open-label, phase 3 study and will enroll ̃160 patients with histologically confirmed BCG-unresponsive, high-risk, non-muscle invasive transitional cell carcinoma of the bladder urothelium (high-grade Ta or T1 tumor, or carcinoma in situ [CIS]) in 2 separate Cohorts, B1 and B2 (̃110 and ̃50 patients, respectively). Cohort B1 will enroll patients with persistent or recurrent CIS with or without concomitant recurrent high-grade Ta/T1 disease, within 12 months of completing adequate BCG therapy. Cohort B2 will enroll patients with recurrent high-grade Ta/T1 disease within 6 months of completing adequate BCG therapy. All patients will receive subcutaneous sasanlimab as a single agent. Efficacy will be assessed at regular intervals by cystoscopy, urine cytology, biopsy, and imaging. The primary endpoint is complete response (CR) and event-free survival (EFS) for Cohort B1 and B2, respectively. Secondary endpoints include duration of CR (Cohort B1 only), EFS (Cohort B1 only), overall survival, time to cystectomy, safety, health-related quality of life, pharmacokinetic parameters, PD-L1 expression, and incidence of anti-drug antibodies. Recruitment of patients in CREST Study Cohort B will be opened in Canada and the United States of America, with other sites in Asia, Australia, and Europe. Clinical trial information: NCT04165317.

LASER ABLATION OF NON-MUSCLE INVASIVE BLADDER TUMORS; ANY ADVANTAGE OVER STANDARD RESECTION PROSPECTIVE COMPARATIVE STUDY

Background: The choice of treatment modality in patients with Non muscle invasive bladder cancer (NMIBC) is one of the most discussed issues in urology.One of major problems in management of NMIBC in high recurrence and progression rates. In recent years, the laser has increasing role in different urological fields.Aim of the Work: Evaluation of the value of adding LASER ablation of the tumor bed after resection of the non-muscle invasive transitional cell carcinoma of the urinary bladder.Patients and Methods: 136 patients with non-muscle invasive bladder cancer randomly divided into two groups: Group 1 underwent Laser ablation of tumor bed after resection (Laser group)(n=68), and Group 2 underwent conventional transurethral resection of bladder tumor (TURBT group) (n=68). Operation time, irrigation time, Catheterization time, postoperative hospital stay, Postoperative clot retention or any postoperative complications, and results after each follow up cystoscopy were collected and compared.Results: after one year follow up for all patients we found that patients who underwent laser ablation after resection has less recurrence or progression rates than patients of the other group which was significant statistically. Also they had less postoperative hospital stay and early catheter removal.Conclusion: laser found that it can decrease the recurrence and progression rates in NMIBC after 1 year follow up, it also found to improve postoperative hematuria and decrease postoperative catheterization time and postoperative hospital stay when compared to conventional TURBT.

Results of Postoperative Instillation of Mitomycin C in Non Muscle Invasive Bladder Cancer after Complete Resection Versus BCG (Recurrence and Progression)

AbstractBackground: Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well-established treatment for preventing or delaying tumour recurrence after tumour resection. However, up to 70% of patients may fail. New protocols and new intravesical agents with improved effectiveness are neededAim of Study: Is to evaluate the oncological outcome as regard progression, local recurrence and side effects of non-muscle invasive transitional cell carcinoma of the urinary bladder managed by complete resection followed by postop-erative intravesical instillation of Mitomycin C compared with BCG.Patients and Methods: This is a prospective study that included 51 patients with non-muscle invasive TCC bladder (Ta and T1) at Urology Department, Al-Azhar University hospitals between 2011 and 2015. Patients divided into two groups, the Mitomycin group received immediate MMC and periodic 6 doses of MMC and the other group, BCG received 6 doses of BCG one dose per week. Follow-up by cystoscope for two years at 3th, 6th, 9th, 12th, 18th, 24th month to detect the recurrence, progression and side effects.Results: The mean age of the patients was 60.58 (37 yrs. - 79 yrs.) in the MMC group and 61.76 (48 yrs-83 yrs) in the BCG group. The main comparison in this study is recurrence rate and progression rate of the tumor. Three patients (11.5%) had recurrence in the 1st year while four patients (15.4%) in the 2nd year with total recurrence seven patients (26.9%) in MMC group.In the BCG group, patients who had a recurrence in the 1st year were, two patients (8%) and three patients (12%) in the 2nd year with total recurrence, five patients (20%).The total progression in two years were 4 pts (15.38%) (One patient (3.8%) in the 1st year) (3 patients (11.5%) in the 2nd year) in the MMC group while were 4 pts (16%) (One patient (4%) in the 1st year) (year 3 patients (12%) in the 2nd year) in the BCG group.Conclusion: Our study confirmed the positive effect of immediate Mitomycin C intravesical instillation in patients who received periodic Mitomycin C instillation and either the positive effect of intravesical instillation of BCG in patients with non-muscle-invasive bladder tumors. Our present study showed that MMC and BCG equally reduced recurrence and progression in NMIBC patients while showed the superiority of MMC regarding to the adverse effects.

Integrated treatment with hyperthermia and chemotherapy for non-muscle invasive bladder cancer

Oncology-applied hyperthermia is a very old form of therapy. In recent years hyperthermia has been investigated with the aim of improving the treatment for non-muscle invasive bladder cancer to prevent relapse and disease progression, in association with mitomycin-C, a well-known chemotherapeutic agent, to enhance its effect. Target patients are those with non-muscle invasive transitional cell carcinoma, showing medium (Ta-T1, G1-2, multifocal, diameter >3 cm) or high (T1, G3, multifocal or rapidly relapsing, CIS) risk for recurrence or progression. The treatment may be prophylactic following tumor eradication, or ablative when tumor cannot be otherwise eradicated. Several studies have shown the benefits of thermochemotherapy with lower risk for relapse than other treatment options, and 66-80% complete responses following ablative treatment. This association of treatments has a synergic therapeutic effect, higher than administering hyperthermia and drug therapy as single treatment.

745 Prognostic performance of different pathological grading schemes in non-muscle invasive transitional-cell carcinoma

745 Prognostic performance of different pathological grading schemes in non-muscle invasive transitional-cell carcinoma

Recurrence and progression in nonmuscle invasive transitional cell carcinoma of urinary bladder treated with intravesical Bacillus Calmette-Guerin: A single center experience and analysis of prognostic factors.

Background:Intravesical Bacillus Calmette–Guerin (BCG) has been the standard of care for the prevention of nonmuscle invasive bladder cancer (NMIBC) recurrence following resection. Attempts to improve on the result by combining it with other agents have largely failed. This study addresses the result of BCG therapy in our patient population and compares the result with our combination BCG and interferon therapy published earlier.Materials and Methods:The medical records of patients diagnosed with NMIBC and treated with transurethral resection and intravesical BCG were reviewed. Univariate analysis was performed on most known prognostic factors. Results were compared to published data on the use of BCG and interferon from the same institution.Results:Thirty-one patients were identified. Median age was 66 (range 33–109), 80.6% were males. Fourteen patients (45%) had ≤ 3 tumors and 18 (58.1%) had T1 lesions. Four patients (12.9%) had Grade 3 tumors and 25 (80.6%) had Grade 2 tumors. One patient (3.2) had concurrent carcinoma in situ and 11 (35.5%) were treated upon initial diagnosis. At 5 years, the relapse-free survival was 61.3% (95% confidence interval (CI) 44.2–78.4%), progression-free survival was 85.6% (95% CI 73.3–97.9%), and overall survival was 93% (95% CI 84.1–100%). Comparison with the BCG and interferon data showed no significant difference.Conclusion:The result of BCG therapy in our patient population is similar to western reported data. Efficacy of BCG alone is equal to BCG and interferon within our institution.

Rare Case of Acute Liver Failure Caused by Diffuse Liver Metastases in a Patient With Non-Muscle Invasive Transitional Cell Carcinoma of the Bladder

Introduction: Acute liver failure (ALF) secondary to infiltration of the liver by malignant cells is unusual, and hematological malignancies are the most common underlying etiology. ALF secondary to liver infiltration from transitional cell bladder cancer is extremely rare. Case Report: A 70-year-old woman with a 2008 history of non-muscle invasive (Stage T1) transitional cell cancer of bladder, treated with transurethral resection of the bladder tumor, presented to the hospital with right upper quadrant pain, fever, and vomiting. Labs showed WBC 12,000, lactate 6.2 mmol/L, and abnormal liver parameters (AST, 416 U/L; ALT, 147 U/L, total/direct bilirubin, 6.1/4 mg%, alkaline phosphatase, 268 U/L, INR, 1.5). Abdominal ultrasound showed multiple gallstones and non-dilated CBD. ERCP showed no CBD stone or evidence of cholangitis. Viral hepatitis, autoimmune serologies, and other laboratory studies for other causes of acute liver failure were negative or non-reactive. A CT scan showed numerous low attenuation masses in the liver and enlarged retroperitoneal lymph nodes, and the bladder appeared normal. A liver biopsy showed sheets of malignant cells. P63 stain was positive, suggestive of metastatic carcinoma of urothelial origin. The patient’s liver synthetic parameters continued to worsen. She developed hepatic coma and expired 6 days after presentation. Discussion: ALF secondary to infiltration of the liver by malignant cells is a well-described entity, with hematological malignancies, including lymphoma and leukemias, being the most common causes. Other metastatic malignancies that rarely can cause ALF include adenocarcinomas and melanoma. ALF secondary to liver infiltration from transitional cell bladder cancer is extremely rare, with only 3 previous cases reported, all with documented muscle invasive (Stage T2) disease. Conclusion: To our knowledge, we report the first case of ALF secondary to non-muscle invasive (Stage T1) transitional cell bladder cancer occurring 5 years after original presentation and presumptive cure.

Highlights from the canadian bladder cancer network.

It is an honour and privilege to introduce this issue of the CUAJ as the recently appointed Associate Editor for our journal. One of the important contributions in this issue includes that of Dr. Pouliot and colleagues from Universite Laval further defining the risk factors associated with renal deterioration after laparoscopic partial nephrectomy.1 The authors suggest that our surgical planning should focus more on limiting resection of normal tissue, careful closure of the collecting system and hemostasis, while paying less heed to early unclamping of vessels as long as warm ischemic time can be limited to 30 minutes. Also, Dr. Abdullah and Dr. Kapoor present a well-timed review of what is a mounting paradigm-shift around the management of castration-resistant prostate cancer (CRPC).2 This article should be required reading for all those who manage patients with prostate cancer. Finally, we are delighted to be able to highlight the recent work from the research team of the Canadian Bladder Cancer Network (CBCN).3 This consortium of Canadian investigators has evolved out of an unmet need due to traditionally underfunded urothelial cancer research. The network has so far compiled the clinical and pathologic data of 2287 contemporary patients who underwent cystectomy, implementing multiple strict quality control procedures to ensure accuracy and concordance of their data. This article focuses on patients who underwent cystectomy for high-grade T1 bladder cancer and confirms the ominous results recently demonstrated in other series.4,5 In this cohort of patients, local tumour upstaging to muscle invasive disease was evident in 48% of cases, with an alarming lymph node involvement of 19.9%. Although the treatment options for non-muscle invasive transitional cell carcinoma are well-described in many guidelines,6 including the recent CUA offering,7 there is little debate that the optimal management of high-grade T1 disease remains a common and vexing dilemma. Most recommendations for high-grade T1 disease include an initial attempt at bladder preservation (grade A) with the option of “early” cystectomy in those with high risk of progression (grade C). The extraordinarily high rates of pathologic upstaging and only modest disease-free survival demonstrated in this and other reports however would suggest the inadequacy of our clinical decision-making based on available tools for risk stratification and current treatment algorithms. Although the present study is limited by selection bias and the lack of certain clinical parameters, the results underscore the need to more effectively identify patients at high risk of progression. Given the propensity towards bladder sparing in Canada and the fact that randomized trials are unrealistic, it is apparent that the time has come to rally support and resources for future collaborative work embodied by the CBCN. Facilitating prospective, multi-institutional registry studies to further identify clinical, pathologic and molecular factors predicting progression is needed to inform us when we should “cut bait” and move on to definitive therapy for this invasive stage of disease.

Non-muscle invasive transitional cell carcinoma of the distal ureter and bladder with lung metastasis: A case report and literature review

INTRODUCTIONNon-muscle invasive transtitional cell carcinoma (TCC) with metastases is exceedingly rare. PRESENTATION OF CASEWe report the case of a 78-year old man with an incidental finding of a non-muscle invasive TCC of the left distal ureter during treatment for Duke's B Colon cancer. Following laparoscopic nephro-ureterectomy (LNU) he had two further superficial recurrences in the bladder over a 14-month period which underwent transurethral resection (TUR). On surveillance imaging for his colorectal cancer follow-up a lung nodule was detected and video-assisted thoracic surgical (VATS) resection of the lesion showed it to be TCC in origin. He was referred to oncology for chemotherapy and remains clinically well. DISCUSSIONA Literature search found only three other such cases and the ureteric TCC is the most likely source of the metastasis. CONCLUSIONThis occurrence is exceedingly rare.

E-cadherin expression as a prognostic factor in transitional cell carcinoma of the bladder after transurethral resection.

To analyze the role of negative versus positive immunoexpression of E-cadherin in recurrence rate of low-grade bladder tumors. A total of 180 patients with unifocal, superficial, low-grade, papillary transitional cell carcinoma of the bladder were included in this study. The E-cadherin expression was evaluated using E-cadherin antibody. The patients were followed up for 36 months. Thereafter, recurrence rate of the tumor was compared between E-cadherin positive and negative groups. Of 180 low-grade carcinomas, E-cadherin immunoexpression was negative in 101 (56%) and positive in 79 (44%) patients. The recurrence rate in negative and positive groups was 65.6% and 37.9%, respectively. Negative in comparison with positive E-cadherin expression was associated with more disease recurrence (P = .045). There is an association between decreased E-Cadherin immunoexpression and tumor recurrence in low-grade and non-muscle invasive transitional cell carcinoma of the bladder.

A rare and unusual case of isolated cerebellar metastasis from a non-muscle invasive transitional cell carcinoma of bladder

Cerebellar metastases from superficial bladder cancer are extremely rare. Bladder cancer is the second most common cancer of the urinary tract. It is the fourth most common cancer in men and eight most common in women in Europe where its incidence is estimated at 104,000 in 2006. Seventy percent1 of bladder cancer is confined to the mucosa (Ta, CIS-T1), but 30% is invasive. The most common solid organs with metastatic spread are lung (24–36%) and liver (21–35%). Brain metastases are rare, with previous estimates at 0.3–8%.2 We present the case of a successfully treated solitary cerebellar metastasis that presented 11 months following resection of organ-confined transition cell carcinoma.

The expression and significance of E-CD and p16 in transitional cell carcinoma of bladder

Objective To investigate the expression of E-CD and p16 in transitional cell carcinoma (TCC) of bladder and the implication. Methods The expression of E-CD and p16 was detected in 50cases of TCC and 10 cases of normal bladder tissue by immunohistochemical technique. Results The positive expression rate of E-CD and p16 in nomal bladder tissue ( 100% ) was significantly higher than that in the TCC (44. 0% and 54. 0% ). The positive expression rate of E-CD in the TCC of grades Ⅰ , Ⅱ, Ⅲ was 68.7%, 57.7% and 25.0%, and that of p16 was 75.0%, 53. 8%, 12. 5%, respectively. The positive expression rate of E-CD and p16 in non-muscle invasive TCC (Tis-T1) was 72.7% and 68. 2%, and that in muscle invasive TCC was 42. 9% and 42. 8% respectively. The positive expression rate of E-CD and p16 in no-lymphatic metastasis was 69. 4% and 63.9%, and that in lympathic metastasis was significantly reduced to 21.4% and 28. 6%. Conclusion E-CD and p16 play an important role in the pathogenesis and development of the TCC and they are helpful to predicting the prognosis of the patients with TCC. Key words: Transitional cell carcinoma of bladder; E-CD; p16

Evaluation of HER2 protein overexpression in non-muscle invasive bladder cancer with emphasis on tumour grade and recurrence

ObjectiveTo evaluate the prognostic value of HER2 expression in non-muscle invasive transitional cell carcinoma (TCC) of the bladder with special emphasis on the high-grade population. Materials and methods (patients)We performed tissue microarrays (TMA) with representative TUR-B specimens from 84 patients with non-muscle invasive transitional cell carcinoma (TCC) of the bladder (40 pT1GII and 44 pT1GIII) treated at our institution. The same pathologist who performed blind immunohistochemical analysis with Hercep test uniformly assigned depth of invasion and grade: 3+ was considered strong positive HER2 overexpression. We also assessed other clinico-pathological variables. ResultsWe detected HER2 protein overexpression in 30/44 (68.2%) pT1GIII lesions and predicted recurrence in this subgroup of bladder TCC (p<0.01). We detected negative HER2 expression in 26/40 (65%) cases with pT1GII TCC, and this condition was more frequent in unifocal tumours, without angiogenesis, with a low recurrence rate and without progression. Recurrence-free survival can also be anticipated by HER 2 expression within pT1GII tumours (p<0.01). ConclusionHER2 expression using Hercep Test™ may be useful to predict recurrence in non-muscle invasive bladder TCC. The potential application of this study, especially regarding prediction of response to BCG, should be prospectively confirmed in multiinstitutional trials.

Loss of Heterozygosis on IFN-α Locus is a Prognostic Indicator of Bacillus Calmette-Guerin Response for Nonmuscle Invasive Bladder Cancer

We evaluated the role of loss of heterozygosity on the interferon-alpha locus to predict the response to bacillus Calmette-Guerin therapy in patients with nonmuscle invasive bladder cancer. A total of 117 consecutive patients were selected, including 77 with nonmuscle invasive bladder cancer and 40 controls. Loss of heterozygosity on the interferon-alpha locus (chromosome 9p21) was assessed in blood and urine samples before transurethral resection. All patients underwent transurethral resection and then 6 weekly bacillus Calmette-Guerin instillations. Those with nonmuscle invasive bladder cancer were assigned to groups 1 and 2 with and without loss of heterozygosity on the interferon-alpha locus, respectively. Of the 77 patients with nonmuscle invasive bladder cancer 39 (50.6%) had loss of heterozygosity on the interferon-alpha locus (group 1) and 38 (49.4%) had no alteration (group 2). Only 1 of 40 controls showed loss of heterozygosity on the interferon-alpha locus. At the end of followup 13 patients in group 1 and 27 in group 2 were alive without recurrence. We noted a significant difference between loss of heterozygosity on interferon-alpha and followup status (dF 01, LR 11.252, p = 0.003). Kaplan-Meier analysis revealed a significant difference in recurrence probability (response to bacillus Calmette-Guerin) and loss of heterozygosity on interferon-alpha (p <0.0001). On multivariate analysis loss of heterozygosity (HR 4.09, 95% CI 2.59-6.28, p = 0.002), grade (grade 3 HR 3.31, 95% CI 1.38-3.35, p = 0.03) and the number of lesions (3 or greater HR 2.31, 95% CI 1.38-3.25, p = 0.03) were independent predictors of the bacillus Calmette-Guerin response. This study highlights the predictive value of loss of heterozygosity analysis on interferon-alpha in patients with nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin.

The Natural History of Non-Muscle-Invasive Transitional Cell Carcinoma of the Bladder

Non-muscle-invasive (NMI) transitional cell carcinoma (TCC) of the bladder is a common disease that recurs frequently and may progress to more sinister invasive disease. In the absence of a molecular tool that can accurately predict an individual's propensity to tumour recurrence and/or progression, urologists utilise prognostic factors to predict patient outcome. To ascertain the value and ranking of known prognostic factors we performed a MEDLINE search using the MeSH heading bladder neoplasm, with classification, epidemiology and mortality as subheadings. Papers describing significant cohorts of patients (&gt;100) were identified and reviewed to ascertain tumour recurrence and progression rates, along with overall and bladder cancer-specific mortality. Factors affecting tumour recurrence, progression and survival were determined. Tumour recurrence and progression rates varied between 46–70% and 6–56% respectively. Multifocality, previous high tumour recurrence rate, positive 3-month check cystoscopy and tumour size were predictive of tumour recurrence. Tumour grade, multifocality and tumour size were predictive of tumour progression. Overall and bladder cancer-specific survival varied between 8–85% and 56–99.4% respectively, and clearly related to duration of patient follow-up. Grade, stage and previous high tumour recurrence rates predicted patient survival. The data obtained regarding prognostic factors are used to describe a rationale follow-up schedule for patients with NMI TCC of the bladder.

Integrated Treatment with Hyperthermia and Chemotherapy for Non-Muscle Invasive Bladder Cancer

Oncology-applied hyperthermia is a very old form of therapy. In recent years hyperthermia has been investigated with the aim of improving the treatment for non-muscle invasive bladder cancer to prevent relapse and disease progression, in association with mitomycin-C, a well-known chemotherapeutic agent, to enhance its effect. Target patients are those with non-muscle invasive transitional cell carcinoma, showing medium (Ta-T1, G1–2, multifocal, diameter &gt;3 cm) or high (T1, G3, multifocal or rapidly relapsing, CIS) risk for recurrence or progression. The treatment may be prophylactic following tumor eradication, or ablative when tumor cannot be otherwise eradicated. Several studies have shown the benefits of thermochemotherapy with lower risk for relapse than other treatment options, and 66–80% complete responses following ablative treatment. This association of treatments has a synergic therapeutic effect, higher than administering hyperthermia and drug therapy as single treatment.

Follow-up of nonmuscle invasive transitional cell carcinoma of the bladder: how and how often?

Nonmuscle invasive bladder cancer represents a heterogeneous disease due to different natural history of its various appearances. The purpose of this article is to review recent literature regarding follow-up strategies. Management of nonmuscle invasive bladder cancer has become more complex in respect to diagnosis, treatment and follow-up. Follow-up should therefore be based on individual patient-risk assessment. In addition to improved diagnosis by fluorescence-guided cystoscopy and other new diagnostic tools like optical-coherence tomography management has concentrated on optimizing different concepts of intravesical therapy. The intent of nonmuscle invasive bladder cancer management is to control recurrence and progression and to identify invasive tumours at the earliest possible stage. To obtain exact staging, besides a proper transurethral resection of bladder, a restaging transurethral resection of bladder should be performed in T1 patients. Data from the literature supports the immediate postoperative intravesical instillation of different chemotherapeutic agents in low-risk patients. Multifocal papillary lesions might necessitate a more intensive adjuvant regimen, whereas intravesical immunotherapy using bacillus Calmette-Guerin is recommended in patients who are at a high-risk of progression. Early cystectomy should be considered in patients with recurrent T1 tumours or refractory carcinoma in situ to avoid unfavourable tumour progression.