Muscle-infiltrating Bladder Cancer Research Articles

Association of HLA-G Expression, Its Genetic Variants and Related Neuro-Immunomodulation with Characteristics of Bladder Carcinoma.

Human leukocyte antigen G (HLA-G) is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities. It belongs to class I non-classical major histocompatibility complex molecules and has been upregulated in various cancer types. In bladder cancer (BC) tumors, the association of HLA-G with cancer progression has to be explained. A total of 89 BC patients and 74 control subjects were genotyped for the HLA-G 14 bp ins/del polymorphism. In urine cell samples, HLA-G mRNA expression was analyzed using real-time PCR. Soluble HLA-G (sHLA-G) serum levels were measured by ELISA. The associations between the HLA-G 14 bp ins/del polymorphism, HLA-G mRNA expression, and/or sHLA-G levels and selected variables including tumor grade, disease stage, body mass index, and heart rate variability (HRV) parameters were evaluated. The protective HLA-G 14 bp ins/ins genotype under the recessive genetic model was associated with lower HLA-G mRNA expression in the BC group (p = 0.049). Significantly higher HLA-G mRNA expression was detected in patients with pT2 + pT3 as compared to those with pTa + pT1 stages (p = 0.0436). Furthermore, higher HLA-G mRNA expression was observed in high-grade muscle-infiltrating BC (MIBC) than in the low-grade non-MIBC group (p = 0.0365). Patients with a level of sHLA-G above 29 U/mL had shorter disease-free survival than patients with lower sHLA-G levels. Furthermore, the opposite HRV correlations with sHLA-G levels in BC patients as compared to controls probably reflect the different roles of HLA-G in health and cancer. Our results suggest the impact of the HLA-G 14 bp ins/del variant, HLA-G expression, and autonomic nervous system imbalance on advanced stages of BC.

Development of an immune-nutritional prognostic index in patients with muscle-infiltrating bladder cancer candidates for radical cystectomy

IntroductionMuscle-infiltrating bladder tumor (MIBT) has a recurrence-free survival (RFS) of 50% at 5 years. Although neoadjuvant chemotherapy (NCT) has increased it by 8%, which group of patients benefits the most from this treatment remains unclear. ObjectiveEvaluate the prognostic value of immune-nutritional status in patients with MIBT who are candidates for cystectomy, and to develop a score that allows identifying patients with a worse prognosis (pT3-4 and/or pN0-1). Material and methodsA retrospective analysis was carried out on 284 patients with MIBT treated with radical cystectomy. Preoperative laboratory tests were analyzed and immune-nutritional indices were calculated. The Kaplan–Meier method was used to calculate the PFS. Cox regression was used for multivariate analysis. ResultsUnivariate analysis showed a statistically significant relationship with leukocyte/lymphocyte index (p = 0.0001), neutrophil/lymphocyte index (p = 0.02), prognostic nutritional index (p = 0.002), and platelet/lymphocyte ratio (p = 0.002). In multivariate analysis, the leukocyte/lymphocyte ratio (p = 0.002) and PNI (p = 0.04) behaved as independent prognostic factors of decreased RFS. Based on these, a prognostic score was developed to classify patients into 3 prognostic groups. Eighty percent of patients with pT3-4 and/or pN0-1 tumors were in the intermediate–poor prognostic groups. ConclusionThe implementation of a precystectomy immune-nutritional score in clinical practice would help in the selection of a group of patients with a more unfavorable pathologic stage and worse PFS. We believe that these patients could benefit more from a NACT.

Prevalence and outcomes of transurethral resection versus radical cystectomy for muscle-infiltrating bladder cancer in the United States: A population-based cohort study

IntroductionAlthough radical cystectomy is considered as the first choice for muscle-invasive bladder cancer (MIBC), there are also concerns regarding the cost of long-term morbidity, loss of body image, and compromised quality of life. Transurethral resection of bladder tumor (TURBT) is a candidate for bladder sparing treatments, but its viability as a substitute for radical cystectomy is questionable. Therefore, we conducted this population-based study to investigate the prevalence of TURBT in the treatments of T2-stage MIBC in the United States, and to compare its therapeutic efficiency with that of radical cystectomy. MethodsInformation on patients with T2-stage bladder cancer (BC) between 2000 and 2017 was extracted from the Surveillance, Epidemiology, and End Results program. The overall survival (OS) and disease-specific survival (DSS) of patients with different interventions were fitted. ResultsA total of 22,074 patients with T2-stage MIBC were enrolled, of whom 14,021 reached the main endpoint. Only 28% of the patients with T2-stage MIBC chose radical cystectomy as the initial surgical treatment, while TURBT was applied as the primary surgical treatment in 66.6% of the patients. The TURBT rate increased significantly with age at cancer diagnosis (40–44 years, 45.5% to > 85 years, 90.9%). The survival rate of patients undergoing TURBT was significantly lower than for those undergoing radical cystectomy (median OS: 1.5 versus 9.7 years; median DSS: 2.7 years versus not reached). Upon multivariable Cox analyses, the OS (HR: 2.34; p < 0.001) and DSS (HR: 2.68; p < 0.001) of TURBT were found to be significantly worse than those of radical cystectomy. ConclusionTwo-thirds of the patients with T2-stage MIBC were treated by TURBT in the United States. However, the long-term follow-up data indicate that the therapeutic efficiency of current TURBT techniques is far less effective than that of radical cystectomy. Further studies are urgently needed to devise the best management strategy for T2 stage bladder cancer.

Our initial experience with the three layers with three-port approach for laparoscopic radical cystectomy.

IntroductionRadical cystectomy (RC) remains the gold standard for the treatment of recurrent high-risk non-muscle-infiltrating bladder cancer (BC) and muscle-infiltrating BC. Currently, there is no uniform standardized procedure for laparoscopic radical cystectomy (LRC).AimTo share our initial experience with the three layers with three-port approach for laparoscopic radical cystectomy (TLTPA-LRC) and to investigate its safety and effectiveness.Material and methodsBetween April 2017 and March 2020, 32 patients with bladder tumors underwent TLTPA-LRC, pelvic lymph node dissection, and extracorporeal construction of the Studer neobladder. The basic characteristics of the patients, clinical pathology, and perioperative and follow-up data were analyzed. We also describe our step-by-step surgical technique for TLTPA-LRC.ResultsThe median operation time was 278.5 min (range: 221–346 min), and the mean estimated blood loss was 233.4 ml (102–445 ml). The rates of intraoperative blood transfusion and postoperative transportation to the intensive care unit after surgery were 12.5% and 100%, respectively. Postoperative pathology showed 7 cases of T1, 20 cases of T2, and 5 cases of T3. Lymph node dissection and surgical margins were both negative. During a median follow-up of 13.5 months, 4 patients had early complications (< 30 days) and no patients had major complications (grade ≥ 3). The patients are now alive without local metastasis and with satisfactory urinary control ability day and night.ConclusionsAlthough the TLTPA-LRC approach requires a certain level of surgical proficiency, it is feasible and serves as a minimally invasive method for selected patients.

Current Perspectives on Immunotherapy in the Peri-Operative Setting of Muscle-Infiltrating Bladder Cancer.

Patients with muscle-infiltrating bladder cancer (MIBC) present a high risk of postoperative recurrence and death from metastatic urothelial cancer despite surgical resection. Before the use of peri-operative chemotherapy, about half (52%) of patients undergoing radical cystectomy had had a relapse of tumor disease within 5 years of surgery. However, when peri-operative cisplatin-based chemotherapy is added to radical cystectomy for patients with MIBC it provides limited benefit in terms of survival, disease recurrence and development of metastases, at the expense of toxic effects. In fact, a significant proportion of patients still recurs and die to metastatic disease. Given the success of immune-oncological drugs in metastatic urothelial cancer, several trials started to test them in patients with non-metastatic MIBC either in neo-adjuvant and adjuvant setting. The preliminary results of these studies in neo-adjuvant setting are showing great promise, confirming the potential benefits of immunotherapy also in patients with non-metastatic MIBC. The aim of this review is to present an overview of developments happening on the introduction of immunotherapy in peri-operative setting in non-metastatic urothelial cancer. Moreover, an analysis of the critical issues regarding how best customize the delivery of immunotherapy to optimize efficacy and minimize the adverse effects, with particular focus on potential prognostic and predictive molecular biomarkers, is done.

Outcomes of patients following dose-dense neoadjuvant chemotherapy for muscle-invasive bladder cancer: Implications for organ-sparing strategies.

426 Background: Locoregional management of muscle-infiltrating bladder cancer (MIBC) after neoadjuvant chemotherapy (NAC) is controversial, because of both the morbidity of radical cystectomy (RC). Bladder preservation may be feasible after complete tumor response. Methods: This single-center retrospective study included 120 MIBC patients (stages ypT2-4aN0-3M0) treated between 2011 and 2017 with up to 6 cycles of neoadjuvant dose-dense Methotrexate, Vinblastin, Doxorubicin and Cisplatin (DD-MVAC). The primary outcome was relapse-free survival (RFS) depending on pathological findings on RC specimens, classified as either pathological complete response (pCR: ypT0N0/x), residual organ-confined disease (yOCD: ypTa/is/1/2N0/x), residual non-organ-confined disease (yNOCD: ypT≥3Nany or ypTanyN1-3). Secondary objectives included the rate of pCR in RC patients, the rate of ypT0 in the intention-to-treat population, and RFS in ypT0 patients according to locoregional management. Results: After a median number of 5 cycles of NAC, RC was performed in 75% of the patients, concurrent radiochemotherapy (CRC) in 11% and cystoscopic surveillance (CS) in 8%. In the intention-to-treat population, the ypT0 rate was 47%. Among 90 patients who underwent RC, 49% achieved pCR, 16% had yOCD and 34% yNOCD. Median follow-up in RC patients alive at last follow-up was 40 months. Three-year RFS was 86% in RC patients with pCR, 69% in patients with yOCD and 21% in patients with yNOCD (p &lt; 0.0001). Outcomes were similar between ypT0 patients treated with either RC or CRC/CS (3-year RFS: 81% vs 100%, p = 0.20). Limitations to this study included its restrospective design and the lower number of patients treated with CRC/CS. Conclusions: Patients reaching ypT0 after dose-dense NAC show improved prognosis regardless of locoregional treatment. Patients with yOCD are frequently cured by RC, as opposed to patients with yNOCD. Prospective trials are needed to compare upfront cystectomy and bladder-sparing management in patients with both pCR or yNOCD.

Expression of B7-H3 in muscle infiltrating bladder cancer and its clinical significance

Objective To investigate the expression of B7-H3 in muscle infiltration bladder transitional cell carcinoma and its clinical significance. Methods The clinical and pathological data of 115 patients with muscle infiltration bladder transitional cell carcinoma who underwent radical surgery were retrospectively analyzed. The expression of B7-H3 in bladder cancer tissues and corresponding paracancerous tissues was detected by immunohistochemical staining, and the relationship between B7-H3 and clinicopathological characteristics was analyzed. Results The positive expression of B7-H3 was mainly in the cytoplasm, presenting brownish yellow granules. B7-H3 had positive expression in all bladder cancer tissues but no expression in paracancerous tissues. The high positive rate of B7-H3 expression in bladder cancer was 68.7%. The abnormal expression of B7-H3 was correlated with the distant metastasis and intravascular tumor thrombi (all P 0.05). The survival analysis result showed that the survival time of the patients with high expression of B7-H3 in the bladder cancer tissues was significantly lower than that of patients with low expression of B7-H3, and the difference was statistically significant (P<0.05). Conclusion The expression of B7-H3 in muscle infiltration bladder cancer tissues is up-regulated and is positively associated with the distant metastasis of bladder cancer and intravascular tumor thrombus. The expression of B7-H3 may indicate poor prognosis of the patients with bladder cancer. Key words: Bladder cancer; Immunohistochemistry; B7-H3; Prognosis

Can re-cTURBT be useful in pT1HG disease as a risk indicator of recurrence and progression? A single centre experience.

Understaging after initial transurethral resection is common in patients with high-risk non muscle infiltrating bladder cancer (NMIBC) and can delay accurate diagnosis and definitive treatment. The rate of upstaging from T1 to T2 disease after repeated transurethral resection ranges from 0 to 28%, although the rate of upstaging may be even higher up to 49% when muscularis propria is absent in the first specimen. A restaging classic transurethral resection of bladder tumour (re-cTURBT) is the better predictor of early stage progression. According to some reports, the rate of positivity for tumor in re-cTURBT performed within eight weeks after initial cTURBT was as high as 18-77%, and in about 40% of the patients a change in tumor stage was reported. We aimed to investigate, in high risk group, the presence of residual tumor following white light classical transurethral resection of bladder tumor (WLre-cTURBT) and the different recurrence and progression rate between patients with persistent or negative (pT0) oncological disease after WLre-cTURBT. A cohort of 285 patients presenting with primitive bladder cancer underwent to WLcTURBT from January 2011 to December 2015; out of them 92 (32.28%) were T1HG. In according to EAU guidelines 2011, after 4-6 weeks all HG bladder cancer patients underwent a WL recTURBT . All patients were submitted to a subsequent followup including cystoscopy every 3 months with multiple biopsies, randomly and in the previous zone of resection; urinary citology on 3 specimens and kidney/bladder ultrasound every 6 months. The average follow-up was 48 months. Following WLre-cTURBT we observed a persistent disease in 18 (15.2%) patients: 14 (77.7%) with a HG-NMIBC and 4 (22.2%) with a high grade (HG) muscle invasive bladder cancer (pT2HG). After follow up of all 92 patients according to the guidelines EAU, we observed recurrence in 36/92 (39.1%) and progression in 14/92 (15.2%). Of 14 NMIBC with persistent disease, 10 patients (71.4%) showed recurrence: 4 patients (40%) were pT1HG with concomitant carcinoma in situ (CIS), 3 patients (30%) multifocal pTaHG, 2 (20%) patients CIS and one patient (10%) a muscle invasive neoplasm (pT2HG). Instead of the group of 48 patients pT0 following WL recTURBT, we observed recurrence in 26 patients (54.1%) and in two patients (4.1%) progressions, who presented after 3 months in association with CIS. The remaining 22 patients (45.9%) with initial pT1HG are still progression free. Multivariate analysis showed that the most important variable of early progression were persistent neoplasm and histopathological findings at WLre-cTURBt (p = 0.01), followed by the Summary No conflict of interest declared. INTRODUCTION Bladder cancer is a common genito-urinary malignancy, with transitional cell carcinoma comprising nearly 90% of all primary bladder tumours. At the first diagnosis 70% to 80% of urothelial tumours are confined to the epithelium, the remainder is characterized by muscle invasion. A significant number of patients with high risk non-muscle invasive bladder tumours (HG-NMIBT) treated with white light classic transurethral resection of bladder tumours (WLcTURBT) and intravesical BCG will progress to invasive disease (1-3). Progression to muscle invasion (pT2) mandates immediate radical cystectomy (4). WLcTURBT is the standard initial therapy for NMIBT, but the high percentage of recurrence after surgery is still an unresolved problem (5). High grade pT1 bladder neoplasm (pT1HG) really represents a therapeutic challenge due to the high risk of progression (about 15-30%) to muscle-invasive disease, usually within 5 years (6). However, no consensus exists regarding the treatment of patients with recurrent bladder tumours that invade the lamina propria (pT1) (7-9). Recent studies suggested that the first cTURBT may be incomplete in a significant number of cases (10). Understaging at the time of the initial transurethral resection is common for patients with high-risk NMIBC and can delay accurate diagnosis and definitive treatment. It is therefore recommended for patients with high-risk disease and in those with large or multiple tumors or when the initial transurethral resection is incomplete, to repeat WLre-cTURBT within 2-6 DOI: 10.4081/aiua.2017.4.272 result of the first cystoscopy (p = 0.002) and presence of CIS (p = 0.02). Following WLre-cTURBt in HG-NMIBC patients we identified in 15% of cases a persistent disease with a 4.3% of MIBC. In the high risk persistent bladder neoplasms group we observed recurrent and progression rate higher than in T0 bladder tumours group (Δ = + 17.3% and = Δ + 62.5%, p < 0.05.

Prognostic factors in muscle-infiltrating bladder cancer (MIBC) treated with an organ-sparing treatment with concurrent gemcitabine (GEM) and radiotherapy (XRT): Results of a patient-based cumulative analysis of seven phase I-II trials.

e15529 Background: GEM is a highly effective radiosensitiser and has been combined with XRT in MIBC after transurethral resection to achieve bladder preservation. Several phase I-II trials were con...

Concurrent gemcitabine (GEM) and radiotherapy (XRT) as organ-sparing treatment for muscle-infiltrating bladder cancer (MIBC): Preliminary results of a patient-based cumulative analysis of seven phase I-II trials.

306 Background: GEM is a highly effective radiosensitiser and has been combined with XRT in MIBC after transurethral resection (TUR) to achieve bladder preservation. Several phase I-II trials confirmed that concurrent GEM and XRT is a feasible treatment able to achieve good disease control and a high rate of organ preservation. We performed a patient-based cumulative analysis of the published trials with concurrent GEM/XRT in MIBC. Methods: Primary data for patients (pts) enrolled in all published studies on GEM/XRT were provided from the institutions. Results: A total of 190 pts were treated in seven phase I-II GEM/XRT trials. The median age was 70 yrs (range 42-87 yrs). The histology was pure transitional in 79% and mixed with squamous features in 21% of the cases. Clinical stage was T2 in 70%, T3 in 21%, and T4 in 8% of the cases, respectively. After TUR, pts received a median XRT dose of 55.5 Gy (range 45-64 Gy) with standard and hypo-fractionated regimes used in 68% and 32% of the cases, respectively. GEM was administered on a weekly or twice-weekly basis, with doses ranging from 10 mg/sqm to 500 mg/sqm; a concurrent administration of cisplatin was planned in 38 pts (20%). Grade ≥ 3 acute and late urinary toxicities were recorded in 7 (4%) and 5 (3%) pts, while grade ≥ 3 acute and late intestinal toxicities were recorded in 20 (10%) and 1 (0.5%) pts, respectively. The complete remission rate was 93.3%. Thirty-six pts (18.9%) experienced a bladder recurrence with 14 pts undergoing cystectomy. The 3- and 5-year survival rates calculated by Kaplan-Meier methods are reported in the table. Conclusions: From this pooled analysis of the clinical outcomes of the pts enrolled in phase I-II studies it appears that GEM/XRT is a treatment with mild toxicity profile, able to achieve a high rate of bladder preservation and producing favorable outcomes compared to other published series for organ-sparing therapy for MIBC. Prospective studies are ongoing to confirm these findings. [Table: see text]

Survival after cystectomy for invasive bladder cancer

Aim To determine the difference in survival after cystectomy between patients presenting with primary muscle infiltrating bladder cancer and patients with progression to muscle infiltration after treatment for initial non-muscle-invasive bladder cancer (NMIBC). Patients and Methods We retrospectively analyzed the files of 188 patients who underwent cystectomy for transitional cell carcinoma between 1987 and 2005. Two groups were defined: patients presenting with muscle-invasive tumours and those progressing to muscle invasion after initial treatment. This second group was further divided into low-intermediate and high risk according to the EAU grouping for NMIBC. Results The 5-year disease specific survival (95% confidence intervals) for all patients was 50%(42–59%); 49%(40–60%) in the primary muscle infiltrating group and 52%(37–74%) in the progressive group ( p = ns). The 5-year disease specific survival in the progressive group according to EAU risk groups was 75%(58–97%) for the initially diagnosed low-intermediate risk tumours and 35%(17–71%) for the initially diagnosed high-risk tumours ( p = 0.015). The percentage of patients with non-locally confined tumours (pT3/4-N0//any pT-N+) was 31%//45% and 24%//46% in the primary muscle infiltrating and progressive group, respectively. Conclusions Despite close observation of patients treated for non-muscle-invasive bladder cancer, the survival of patients who progress to muscle invasion is not better than survival of patients presenting with primary muscle infiltrating cancer. Patients with high-risk non-invasive tumours (EAU risk-categories) who progress to muscle-invasive disease have a worse prognosis compared to patients with low or intermediate risk tumours.

Techniques et innovations en radiothérapie pour le traitement conservateur des cancers infiltrants localisés de vessie

Radical cystectomy is the treatment of choice for nonmetastatic, muscle-infiltrating bladder cancer. However, bladder-sparing approaches can be discussed in carefully selected patients. Bladder-preservation protocols aim to guaranty local control and survival with a functional bladder and a good quality of life. Such strategies include combinations of transurethral resection and radiochemotherapy, partial cystectomy and brachytherapy, radiotherapy-cystotomy and electrontherapy. Strict selection criteria and close follow-up are mandatory. New irradiation techniques hold the promise to improve local control by selectively boosting the dose to the tumor while better sparing the organs at risk. Such advances include the use of multimodal imaging, image-guided radiotherapy, concomitant boost with conformal irradiation+/-intensity modulated radiation therapy. Brachytherapy, either high-dose or pulsed-rate, is a promising technique for selected cases. Highly-conformal irradiation with tumor tracking using the Cyberknifetrade mark technology may also provide opportunities to boost the tumor while reducing toxicities. Specific innovative irradiation techniques are discussed.

Bladder-sparing therapy for muscle-infiltrating bladder cancer

Radical cystectomy is the treatment of choice for nonmetastatic, muscle-infiltrating bladder cancer. Several researchers have proposed the use of a bladder-sparing approach in carefully selected patients. Strict selection criteria and close follow-up are needed for bladder-preservation protocols. Although repeated transurethral resection of bladder tumors or partial cystectomy might be offered to high-risk patients, combined protocols with transurethral resection of bladder tumors and chemotherapy, with or without additional radiotherapy, seem to provide the best results, with 5-year survival rates of about 50%. Even if the chance of preserving the bladder is appealing, and despite evidence of some promising results, these protocols should still be considered investigative because, as yet, there are no randomized trials available that compare cystectomy with bladder-sparing surgery.

Prognostic value of cell cycle regulatory proteins in muscle-infiltrating bladder cancer

The aims of this study were to investigate the expression levels of proteins involved in cell cycle regulation in specimens of bladder cancer and to correlate them with the clinicopathological characteristics, proliferative activity and survival. Eighty-two specimens obtained from patients affected by muscle-invasive bladder cancer were evaluated immunohistochemically for p53, p21 and cyclin D1 expression, as well as for the tumour proliferation index, Ki-67. The statistical analysis included Kaplan-Meier curves with log-rank test and Cox proportional hazards models. In univariate analyses, low Ki-67 proliferation index (P = 0.045) and negative p21 immunoreactivity (P = 0.04) were associated to patient's overall survival (OS), but in multivariate models p21 did not reach statistical significance. When the combinations of the variables were assessed in two separate multivariate models that included tumour stage, grading, lymph node status, vascular invasion and perineural invasion, the combined variables p21/Ki-67 or p21/cyclin D1 expression were independent predictors for OS; in particular, patients with positive p21/high Ki-67 (P = 0.015) or positive p21/negative cyclin D1 (P = 0.04) showed the worst survival outcome. Important alterations in the cell cycle regulatory pathways occur in muscle-invasive bladder cancer and the combined use of cell cycle regulators appears to provide significant prognostic information that could be used to select the patients most suitable for multimodal therapeutic approaches.

Primary Cisplatin, Methotrexate and Vinblastine Chemotherapy With Selective Bladder Preservation for Muscle Invasive Carcinoma of the Bladder: Long-Term Followup of a Prospective Study

Primary Cisplatin, Methotrexate and Vinblastine Chemotherapy With Selective Bladder Preservation for Muscle Invasive Carcinoma of the Bladder: Long-Term Followup of a Prospective Study

Transitional cell carcinoma in patients with spinal cord injury: a high risk malignancy?

Objectives. To study bladder cancer incidence in patients with spinal cord injury (SCI) in Germany, Switzerland, and Austria. SCI is associated with neurogenic bladder dysfunction. These patients are at an increased risk of developing bladder malignancies. Methods. A questionnaire was mailed to all SCI centers in these countries. The number of patients with SCI treated between 1995 and 1999, and the data of all patients with SCI with bladder cancer were recorded. Results. The charts of 43,561 patients were reviewed. Of these, 48 patients (0.11%) developed bladder cancer. The data of 8 female and 29 male patients were fully available. The mean age was 53.3 years. Bladder management was reflex voiding in 18 patients, intermittent catheterization in 12 patients, and an indwelling catheter in 7 patients. Twelve patients were smokers. The mean time between SCI and the first bladder cancer diagnosis was 22.6 years. Thirty-two percent had superficial cancers, 8% had carcinoma in situ, and 60% presented with muscle-infiltrating tumors; 81% had urothelial cancer and 19% squamous cell cancer. Thirteen patients rarely had urinary tract infections (UTIs), 9 had more than 10 UTIs annually, and 15 had chronic UTIs. Conclusions. The bladder cancer incidence in patients with SCI and in the general population is comparable. More than 60% of the patients with SCI, however, initially presented with muscle-infiltrating bladder cancer. Indwelling catheters and chronic UTIs were common in patients with bladder cancer. Immunologic pathologic mechanisms and a prolonged exposure to carcinogens may be involved in bladder cancer carcinogenesis in patients with SCI.

Current perspectives in muscle invasive bladder cancer

Muscle-infiltrating bladder cancer should be dealt with in a multimodality approch with collaboration between the urologist, medical oncologist and radiotherapist. Neo-adjuvant chemotherapy has not been proven to improve survival, but may be useful in programs of bladder preservation. Response to M-VAC neo-adjuvant chemotherapy is an important prognostic factor, but may represent patient selection factors. It is not known whether it is better to administer chemotherapy in the neo-adjuvant or in the adjuvant setting, that may spare some patients unnecessary chemotherapy. The international adjuvant chemotherapy trial coordinated by the EORTC (protocol 30994) will hopefully clarify some of the unanswered questions concerning whether or not adjuvant chemotheraphy immediately following cystectomy improves survival.

Partially wedged beams improve radiotherapy treatment of urinary bladder cancer

Background and purpose: Partially wedged beams (PWBs) having wedge in one part of the field only, can be shaped using dynamic jaw intensity modulation. The possible clinical benefit of PWBs was tested in treatment plans for muscle-infiltrating bladder cancer. Material and methods: Three-dimensional treatment plans for 25 bladder cancer patients were analyzed. The originally prescribed standard conformal four-field box technique, which includes the use of lateral ordinary wedge beams, was compared to a modified conformal treatment using customized lateral PWBs. In these modified treatment plans, only the anterior parts of the two lateral beams had a wedge. To analyze the potential clinical benefit of treatment with PWBs, treatment plans were scored and compared using both physical parameters and biological dose response models. One tumour control probability model and two normal tissue complication probability (NTCP) models were applied. Different parameters for normal tissue radiation tolerance presented in the literature were used. Results: By PWBs the dose homogeneity throughout the target volume was improved for all patients, reducing the average relative standard deviation of the target dose distribution from 2.3 to 1.8%. A consistent reduction in the maximum doses to surrounding normal tissue volumes was also found. The most notable improvement was demonstrated in the rectum where the volume receiving more than the prescribed tumour dose was halved. Treatment with PWBs would permit a target dose escalation of 2–6 Gy in several of the patients analyzed, without increasing the overall risk for complications. The number of patients suitable for dose escalation ranged from 3 to 15, depending on whether support from all or only one of the five applied NTCP model/parameter combinations were required in each case to recommend dose escalation. Conclusion: PWBs represent a simple dose conformation tool that may allow radiation dose escalation in the treatment of muscle-infiltrating urinary bladder tumours.

CYSTECTOMY FOR BLADDER CANCER: A CONTEMPORARY SERIES

To validate the current TNM staging system, we analyzed our contemporary experience with 300 cystectomies. The pathological material and medical records of 300 patients treated with cystectomy were reviewed, and the new TNM classification was adopted. The median followup of patients with no evidence of disease was 65 months, and overall survival rate was 45% with a median survival of 50 months. In a Cox regression analysis only patient age, pT stage and neoadjuvant chemotherapy were significant factors for survival. The disease specific survival was 67% with a median survival of 94 months. In a multiple proportional hazards analysis only pT stage and previous chemotherapy were significant factors of disease specific survival. A significant difference was seen in the overall and disease specific survival between patients with organ confined and nonorgan confined tumors. We did not observe a difference in the survival rate among patients with pT4a to pT3 tumors. Significant differences were not seen in survival rates between sexes or among patients of different age groups. Transitional cell carcinoma was the predominant histological type, and no significant difference was found in patient outcome among the different histological subtypes. Bladder cancer can be categorized into organ confined and nonorgan confined tumors. This dichotomous grouping is better suited for evaluating adjuvant clinical trials. The pT stage of the bladder and prostate should be prospectively analyzed together to better define the clinical implications of prostatic involvement. In our opinion the histological subtypes do not affect outcome.

FEASIBILITY OF TRANSURETHRAL RESECTION FOR MUSCLE INFILTRATING CARCINOMA OF THE BLADDER: LONG-TERM FOLLOWUP OF A PROSPECTIVE STUDY

Purpose We analyzed the long-term results of radical transurethral resection for the treatment of a large series of patients with muscle infiltrating bladder cancer entered into a prospective study to determine progression predictive factors. Materials and Methods The study included 133 patients with invasive bladder cancer treated by radical transurethral resection who had negative biopsies of the muscle layer of the tumor bed. Followup was more than 5 years for all subjects and more than 10 years in 59 (44.4%). A comparative nonrandomized study was performed of a control group of 76 patients with invasive pathological stage pT2-3a, N0-3 bladder cancer treated by cystectomy. In those patients treated by radical transurethral resection univariate and multivariate analyses were performed to establish clinical progression predictive factors. Results At 5 and 10 years of followup cause specific survival rates were 80.5 and 74.5%, and bladder preservation rates were 82.7 and 79.6%, respectively. No significant difference was noted in terms of cause specific survival, with respect to the control group. The initial presence of associated bladder carcinoma in situ was the only independent progression predictive factor. Conclusions For patients with invasive bladder cancer radical transurethral resection is justified when the tumor is clinically limited to the muscular layer and when all biopsies of the periphery and depth of the tumor bed show muscular tissue negative for tumor cells. Patients with initial associated bladder carcinoma in situ should not be excluded from this treatment but endovesical bacillus Calmette-Guerin immunotherapy should be administered and a closer followup is recommended.