Accuracy of FDG-PET/CT for Response Evaluation of Muscle-Invasive Bladder Cancer following Neoadjuvant or Induction Chemotherapy.

INTRODUCTION: The aim of the study was to confirm the diagnostic accuracy of a second FDG-PET/CT following neoadjuvant or induction chemotherapy (NAIC) prior to radical cystectomy for patients with localized muscle-invasive bladder cancer (MIBC). METHODS: Retrospective review of 62 consecutive patients with MIBC, that had a first FDG-PET/CT between April 2016 and September 2021. Patients then underwent NAIC, followed by a second FDG-PET/CT and radical cystectomy. Patients with no hypermetabolism in the bladder and lymph nodes on the second FDG-PET/CT were considered metabolic complete responders, while patients with no evidence of residual disease on histopathology were considered pathologic complete responders. The accuracy of the second FDG-PET/CT to distinguish complete responders from patients with residual disease was calculated, with histopathology as gold standard. RESULTS: Of 62 patients, 1 was lost to follow-up, 5 died before radical cystectomy, 5 had delay >2 months between the second FDG-PET/CT and radical cystectomy, and 6 did not undergo radical cystectomy and instead underwent alternative treatment. The study cohort comprised 45 patients, 39 males and 6 females, with an age of 66 ± 6 years. In comparison to histopathology, FDG-PET/CT provided (i) sensitivity of 95% and specificity of 42%, for the overall disease; (ii) sensitivity of 100% and specificity of 36%, for the primary tumor only; and (iii) sensitivity of 97% and specificity of 30%, for the lymph nodes only. CONCLUSION: FDG-PET/CT has over 95% sensitivity for distinguishing complete responders from patients with residual disease. Thus, FDG-PET/CT can be used for early response evaluation following NAIC to identify patients that did not completely respond to chemotherapy and may require alternative treatment pathways.

Efficacy and tolerance of one-third full dose bacillus Calmette-Guérin maintenance therapy every 3 months or 6 months: two-year results of URO-BCG-4 multicenter study.

OBJECTIVES: To assess bacillus Calmette-Guérin maintenance treatment schedule for non-muscle invasive bladder cancer at 2 years, using one-third of the full dose and fewer instillations every 3 months or 6 months. METHODS: This was a prospective, randomized, multicenter study. All patients had an intermediate- or high-risk non-muscle invasive bladder cancer. They received three weekly instillations of one-third dose bacillus Calmette-Guérin every 6 months (group I) and two weekly instillations every 3 months (group II) during 3 years. In the two schedules we assessed efficacy, tolerance, leukocyturia and prostate-specific antigen. RESULTS: No significant difference was observed between the two groups for recurrence at 6, 12 or 18 months. At 2 years, tumor recurrence was observed in 10.9% and muscle invasion in 2.9% of cases. Bacillus Calmette-Guérin tolerance was comparable - the adverse events score was 0.8 in group I and 1 in group II (P = 0.242). No statistical correlation was observed between the adverse events score over 2 years, either for leukocyturia (P = 0.8891) or prostate-specific antigen level (P = 0.7155). Leukocyturia level was not significantly associated with tumor recurrence or progression. CONCLUSION: One-third dose maintenance bacillus Calmette-Guérin is effective with no impact on tumor recurrence or muscle invasion. Furthermore, there seems to be no difference in tumor response or side-effects between patients receiving two or three maintenance instillations every 3 months or 6 months. In clinical practice, the use of leukocyturia or total prostate-specific antigen levels do not appear to be useful in predicting bacillus Calmette-Guérin toxicity.

Testicular-sparing surgery for bilateral or monorchide testicular tumours: a multicenter study of long-term oncological and functional results.

OBJECTIVE: To review long-term oncological and functional outcomes of testicular-sparing surgery (TSS) in men presenting with bilateral or monorchide testicular tumours at one of five reference centres for testicular neoplasm and infertility. PATIENTS AND METHODS: We review 25 cases of bilateral synchrone and metachrone testicular tumours treated in five academic centres between 1984 and 2013. Clinical, biological, ultrasonography and pathological tumour findings, overall survival (OS) times, local or metastatic recurrence, pre- and postoperative hormonal profile, paternity and the need for androgen substitution were assessed. RESULTS: Eleven patients with a bilateral synchrone tumour and 14 patients with a testicular tumour on a solitary testicle underwent a tumorectomy. The mean (sem) patient age was 31.9 (1.04) years, total testosterone level was 4.5 (0.57) ng.mL and tumour size was 11.66 (1.49) mm. Tumour types were as follows: 11 seminoma, nine non-seminomatous or mixed germ cell tumours, four Leydig tumours, and one hamartoma. Frozen-section examination was performed in 14 patients, and matched the final pathological analysis in 11 patients. There was an OS rate of 100% and three patients (12%) presented with a local recurrence after a mean follow-up of 42.7 months. Radical orchiectomy was performed for six patients. No patient with a preserved testicle required androgen therapy; the mean postoperative total testosterone level was 4.0 ng/mL. No patient remained fertile after radiation therapy. CONCLUSIONS: TSS for bilateral testicular tumour is safe and effective in selected patients, and should be considered to avoid definitive androgen therapy. Adjuvant radiotherapy remains poorly described in the literature, leading to adjuvant treatment heterogeneity for testicular tumours.

Oncologic outcomes and survival in pT0 tumors after radical cystectomy in patients without neoadjuvant chemotherapy: results from a large multicentre collaborative study.

PURPOSE: To assess the postsurgical survival of patients with urothelial carcinoma of the bladder with pT0 tumor at pathologic examination of cystectomy specimens. METHODS: A multi-institutional, retrospective database was analyzed with data from 4758 radical cystectomy (RC) patients who underwent RC without neoadjuvant chemotherapy and who were diagnosed with pT0 on the basis of the pathologic specimen. Survival curves were estimated. A multivariate Cox model was used to evaluate the association between prognosis factors and disease recurrence or survival. RESULTS: Overall, 258 patients (5.4%) were included in the study. The median age was 64 years. At last resection, 171 tumors were invasive (at least pT2), and 87 were not. Median follow-up was 51 months. At multivariate analysis, initial location of the tumor and absence of lymphadenectomy were associated with tumor recurrence (P = 0.03 and P = 0.005, respectively) and specific mortality (P = 0.005 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of this situation. Cancer-specific and recurrence-free survival rates were 89 and 85%, respectively, at 5 years and 82 and 80%, respectively, at 10 years. CONCLUSIONS: Despite acceptable oncological outcomes, patients with a pT0 tumor at the time of RC are still at risk of recurrence and progression and should not be considered to be entirely cured. In this population, stringent follow-up according to current recommendations should be effective.

Bladder cancer in patients after organ transplantation.

PURPOSE OF REVIEW: Bladder cancer development in organ transplant recipients remains a complex problem to manage as it has been demonstrated that the clinical course seems worse than in the general population. Most of the reports on bladder cancer after organ transplantation were done for kidney transplantation. Both virally and nonvirally are involved in bladder tumor development. The immunosuppressed status of the transplant recipients renders the screening, the therapeutic management, and the post-treatment surveillance very difficult. RECENT FINDINGS: With the increase of organ transplantation, especially renal transplantation, graft survival, and age of donor and recipient, urological cancer, including bladder cancer, become a critical problem affecting the survival. The advent of the new immunosuppressed drugs, mTOR inhibitors, leads to the hope of improving both survivals of the graft and of the recipients. SUMMARY: The molecular pathway P13K/Akt/mTOR is frequently activated during human solid tumor development and progression. However, mTOR inhibitors are also used in order to avoid renal allograft rejection. The combination of both actions could significantly improve graft and organ recipient survival and could provide progresses in targeted therapy management of bladder cancer.

Tyrosine-kinase inhibitors in the treatment of muscle invasive bladder cancer and hormone refractory prostate cancer.

OBJECTIVES: Various protein kinases are known to be activated in cancer cells and drive tumor growth and progression. In metastatic renal cell carcinoma tyrosine-kinase inhibitors (TKIs) have achieved significant progression-free and overall survival improvements. For bladder and prostate cancers TKIs may also be considered as a promising treatment option. Our aim was to report the most relevant published articles to support the interest of the use of TKIs in the treatment of bladder and prostate cancer. METHOD: PubMed database and bibliographies of retrieved articles were reviewed. The key words used were tyrosine-kinase inhibitor, protein-kinase inhibitor, hormone refractory prostate cancer, muscle invasive bladder cancer. The most relevant publications from basic science and clinical randomized controlled studies were summarized and analyzed. RESULTS: Regarding bladder cancer, TKI treatment is one of the most studied therapeutic strategies in the field of targeted therapy. Indeed, it has been suggested that targeting TK alone and/or in association with cytotoxic chemotherapy may represent a promising option for treating locally advanced and/or metastatic bladder cancer. Concerning hormone refractory prostate cancer (HRPC), collected data are still confusing. Basic science studies found an interesting expression of EGF and VEGF receptors on cancer cells supporting the idea that TKIs could be efficient in HRPC. Nonetheless most of published clinical phase II studies found a weak effect on symptoms and quality of life without any decrease in PSA levels or overall survival. CONCLUSION: TKIs have not yet achieved in bladder and prostate cancers similar efficacy to what has been obtained in metastatic renal cell carcinoma. Further studies are needed to establish the place of such an approach in non renal tumors.

Oncological risk of laparoscopic surgery in urothelial carcinomas.

OBJECTIVE: To assess the oncological safety of laparoscopic procedures for the management of urothelial carcinomas of the urinary tract. METHODS: Data on laparoscopic management of urothelial carcinomas in the literature were analysed using MEDLINE and by matching the following keywords: urological malignancies, upper tract tumours, bladder carcinomas, laparoscopic approach, recurrence, follow-up and metastasis site. RESULTS: Minimally invasive techniques are being used increasingly in the management of these tumours and successfully achieving the benefits of lower blood loss and more rapid patient recovery. To date, no evidence level 1 information is available and published series of these technically challenging cases are small and follow-up limited. Short to medium term follow-up appears encouraging in terms of recurrence and survival rates, but long-term data are immature compared to the established open techniques these procedures seek to duplicate. Specific concerns in terms of the oncologic safety of laparoscopy, especially with regard to the pneumoperitoneum, tumour manipulation and specimen extraction are addressed. Port-site metastases and tumour seeding are rare events and appear to be mainly related to the grade and stage of the tumour. Specific precautions are required to minimise these risks. CONCLUSION: Oncological results of the laparoscopic approach are difficult to compare with those of open surgery. However, recent series have not reported unusual tumour dissemination or a higher rate of recurrence with this approach. Laparoscopic techniques are not yet standard of care in invasive urothelial carcinomas. Long-term assessment is ongoing and awaited.

The expression of Twist has an impact on survival in human bladder cancer and is influenced by the smoking status.

OBJECTIVES: Twist is considered as transcription factor that regulates epithelial mesenchymal transition (EMT) by at least inhibition of E-cadherin expression. EMT is a key event in the tumor invasion process. The purpose of this study is to investigate the expression of Twist but also those of E- and N-cadherin in human primary bladder tumor and to evaluate its prognostic value. As smoking cigarettes is a strong bladder cancer risk factor, we tried to evaluate the impact of the tobacco status on these molecular abnormalities. MATERIALS AND METHODS: To delineate on the oncogenic role for Twist in human bladder cancer, we evaluated the E- and N-cadherin but also Twist expression (n = 70) by immunohistochemistry. We evaluated the prognostic value of these expressions. Moreover, we tried to correlate these protein expressions to the smoking status of the patients. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. RESULTS: Of the 70 bladder tumors, 28 (40%) cases were positive for Twist expression, 16 (23%) cases were negative for E-cadherin expression, and 12 (17%) were positive for N-cadherin expression. When categorized into negative vs. positive expression, Twist was associated with the stage (P = 0.001), the grade (P < 0.001), the progression (P = 0.02), and the E-cadherin expression (P = 0.01). Moreover, positive Twist expression clearly predicted poorer PFS (P = 0.02). In the multivariate analysis, both positive Twist expression and loss of E-cadherin expression were independent prognostic factors for PFS (P = 0.046 and P = 0.001, respectively) and only loss of E-cadherin expression for the OS (P < 0.001). We also demonstrated that almost 60% (16/28) of patients with Twist-positive expression were current smokers at the time of the diagnosis, corroborating the fact that smoking modulates the expression of EMT markers including Twist. CONCLUSION: Positive Twist expression may be a useful prognostic marker for patients with bladder cancer. Its expression seems to be correlated to the tobacco status of the patients.

Molecular targeting in the treatment of either advanced or metastatic bladder cancer or both according to the signalling pathways.

PURPOSE OF REVIEW: An estimated 300,000 new cases of bladder cancer worldwide are diagnosed annually. Although new cytotoxic chemotherapeutic agents for either advanced or metastatic bladder cancer or both are used, no improvement in survival has been observed. Indeed, the 5-year survival rate of metastatic bladder cancer is very low (6%). The target-directed approach is an attractive challenge for treating specific genetic alterations involved in progression and metastasis development. This article aims to describe the new targeted therapies available to cure advanced cancer or metastatic bladder cancer or both according to the signalling pathways potentially involved. RECENT FINDINGS: The rapidly expanding understanding of the pathogenesis of bladder cancer at the molecular level has led to the identification of signalling pathways involved in this disease and provided molecular targets for new biological agents directed against tumorigenesis and progression. The recent results of clinical trials have not only highlighted the need to select patients who could benefit from such a therapy but also the fact that oncology has completely entered into a new era. SUMMARY: Toxic chemotherapeutic agents are slowly being supplemented by a new generation of drugs that recognize specific targets in or on cancer cells. Recent technological advances in pharmacogenomics and proteomics have led to an improvement in identifying biomarkers predictive of response and thereby to identify patients who would be more likely to respond to such a therapy. There is a real hope to improve both the efficiency and the tolerability of bladder cancer treatment.

N-cadherin as a novel prognostic marker of progression in superficial urothelial tumors.

PURPOSE: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion and spreading. In bladder cancer, loss or reduced E-cadherin expression has been associated with poor survival, and aberrant expression of N-cadherin has been associated with the invasive phenotype of bladder carcinoma cells. The purpose of this study was to investigate whether N-cadherin expression was associated with the bladder tumor progression. EXPERIMENTAL DESIGN: E-cadherin and N-cadherin expression was evaluated by immunohistochemistry in 101 tumors (pT1 and pT2-T3) and by reverse transcription-PCR analysis and immunohistochemistry in 28 other fresh frozen tumors (pT(a), pT1, and pT2-T3). RESULTS: N-cadherin expression was absent in normal urothelium, appeared in stage pT1, and increased in pT2-pT3 tumors. In most cases, increased N-cadherin expression in invasive tumors was associated with loss of E-cadherin expression. Progression-free survival and multivariate analyses revealed that N-cadherin expression is an independent prognostic marker for pT1 tumor progression. Analysis of the 28 frozen tumors by immunohistochemistry and reverse transcription-PCR showed a good correlation between protein and gene expression in pT1 and pT2-T3 tumors. Interestingly, in pT(a) tumors, N-cadherin was not immunodetected, whereas mRNA was present in 50% of cases. CONCLUSION: Regulatory defects in the N-cadherin promoter, abnormalities at the translational, or protein processing levels could explain the discrepancies between protein and mRNA expression. Most importantly, this study identified N-cadherin as a novel prognostic marker of progression in superficial urothelial tumors. Clearly, N-cadherin acts in an invasive mode in bladder cancer, but whether it has a primary role in urothelial neoplastic progression has yet to be investigated.

Gefitinib inhibits the growth and invasion of urothelial carcinoma cell lines in which Akt and MAPK activation is dependent on constitutive epidermal growth factor receptor activation.

PURPOSE: Abnormally high levels of epidermal growth factor receptor (EGFR) protein are associated with advanced tumor stage/grade. The objective of this study was to evaluate the effects of the specific EGFR tyrosine kinase inhibitor gefitinib on activation of the Akt and mitogen-activated protein kinase (MAPK) pathways in human urothelial cell carcinoma (UCC) cell lines and to identify potential markers of gefitinib responsiveness in biopsy samples of UCC. EXPERIMENTAL DESIGN: Changes in markers of UCC growth and invasion after exposure to gefitinib were studied in six human UCC cell lines expressing various levels of EGFR. The findings were related to activation of Akt and MAPK. We studied the influence of gefitinib on intraepithelial expansion of the responsive 1207 cell line. EGFR, Akt, and MAPK activation was studied by Western blot analysis of a panel of 57 human UCC. RESULTS: Gefitinib had a growth-inhibitory and anti-invasive effect in two of six UCC cell lines (i.e., 647V and 1207). Gefitinib was also able to block the expansion of 1207 at the expense of normal urothelial cells. These effects did not depend on the level of expression of EGFR but they were associated with the down-regulation of MAPK and Akt activity; in 1207 cells, gefitinib activity was associated with p27 up-regulation and p21 and matrix metalloproteinase-9 down-regulation. Similarly, the Akt and MAPK pathways were found to be strongly phosphorylated in association with EGFR activation in a subset of human UCC specimens. CONCLUSIONS: Activation of EGFR, Akt, and MAPK defines a subset of UCC which might provide information for the identification of gefitinib responders.

FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder.

FGFR3 and TP53 mutations are frequent in superficial papillary and invasive disease, respectively. We used denaturing high-performance liquid chromatography and sequencing to screen for FGFR3 and TP53 mutations in 81 newly diagnosed urothelial cell carcinomas. Tumors were classified as follows: 31 pTa, 1 carcinoma in situ, 30 pT1, and 19 pT2-T4. Tumor grades were as follows: 10 G1, 29 G2, and 42 G3. FGFR3 mutations were associated with low-stage (P < 0.0001), low-grade (P < 0.008) tumors, whereas TP53 mutations were associated with high-stage (P < 0.003), high-grade (P < 0.02) tumors. Mutations in these two genes were almost mutually exclusive. Our results suggest that FGFR3 and TP53 mutations define separate pathways at initial diagnosis of urothelial cell carcinoma.

[Atypical cysts and risk of renal cancer: value and danger of the Bosniak classification]. / Kystes atypiques et risque de cancer du rein. Intérêt et "danger" de la classification de Bosniak.

OBJECTIVE: The objective of this study was to devaluate the risk of renal cancer in patients with atypical renal cysts and to compare radiological data used to establish the Bosniak classification with clinical or histological data. MATERIAL AND METHOD: We performed a retrospective study on 37 patients managed in our establishment for atypical renal cyst between January 1995 and April 2003. The following criteria were analysed: gender, age, clinical examination and circumstances of discovery imaging findings, Bosniak classification, treatment modalities and follow-up data. These criteria were compared in two populations according to the presence or absence of associated renal cancer. RESULTS: In this series, 6 patients presented a stage II cyst. No cancer was demonstrated in this group of cysts. Ten patients presented a stage IIF cyst and 2 cancers were detected in this group (i.e. 20%). Fourteen patients presented a stage III cyst, with a cancer in 4 cases (30%) and 7 patients presented a stage IV cyst with 6 cancers (86%). CONCLUSION: The Bosniak classification is currently the reference classification fr the diagnosis of cystic diseases of the kidney. Although stages I and II (cysts with minor changes not requiring surveillance) and stages III and IV (suspicious malignant cysts which require surgical exploration) raise few diagnostic problems, stage IIF (indeterminate cyst requiring radiological surveillance) may be the source of diagnostic difficulties with a risk of missing an associated renal cancer.

[Conservative management of Corynebacterium urealyticum encrusted cystitis]. / Cystite incrustante a corynebacterium urealyticum: traitement conservateur.

The authors report the case of a 75-year-old patient who developed Corynebacterium urealyticum encrusted cystitis six months after open prostatectomy, complicated by vesicocutaneous fistula, which required bladder catheterization for several days. Encrustation of the bladder wall induced marked bilateral ureteropyelocaliceal dilatation without renal failure. Medical treatment by antibiotic therapy and oral acidification of the urine allowed regression of the plaques and resolution of the dilatation.

[Simultaneous embolization of a large arteriovenous fistula and a renal pseudoaneurysm]. / Embolisation simultanée d'une large fistule artério-veineuse et d'un pseudo-anévrysme rénal.

The authors report the cases of a 41-year-old woman with a large arteriovenous fistula between a branch of the renal artery and the main renal vein in the renal hilum and a peripheral pseudoaneurysm secondary to a knife wound to the kidney. These lesions were successfully treated by embolization. In the light of this case, the authors illustrate the possibility of performing more than one embolization on the same kidney and emphasize the successful embolization of a large, high-flow arteriovenous fistula.

[Bladder leiomyoma treated by transurethral endoscopic resection]. / Le léiomyome de vessie traité par résection endoscopique transuréthrale.

We report a case of intravesical bladder leiomyoma in a 47-year-old patient presenting with recurrent macroscopic haematuria. The diagnosis was strongly suspected on CT and cystoscopy. Treatment consisted of transurethral resection of the mass. No recurrence has been observed with a follow-up of two years. In the light of this case, the authors discuss the diagnosis and treatment of bladder leiomyoma.

[Genetic cause of male infertility and molecular biology]. / Infertilité masculine de cause génétique et biologie moléculaire.

At the present time, 15% of couples experience reproduction difficulties. Surgical collection of spermatozoa associated with the intracytoplasmic sperm injection technique (ICSI) resolves the problems of male infertility formerly considered to be irreversible, regardless of its aetiology. Molecular biology now allows evaluation of the genetic dimension of male infertility. Although it demonstrates the multiple aetiologies of male infertility, it also reveals the gaps in our knowledge and the extent of the task that has yet to be accomplished. Microdeletion of the Y chromosome, detected in 2% to 20% of infertile patients with a disorder of spermatogenesis, has already been well documented. All of the genes involved on the Y chromosome (DAZ, RBMY, etc.) in infertile patients have been shown to be involved in spermatogenesis. Testing for other genes of the genome would also be useful. However, the unknown outcome of these abnormalities with successive generations raises a number of questions. In this article, the authors describe the main genes involved in spermatogenesis as demonstrated by molecular biology.

[Management of severe renal trauma]. / Prise en charge actuelle des traumatismes graves du rein.

OBJECTIVE: To analyse the progress in the management of severe renal trauma (Chatelain stage 3 and 4) over a period of 11 years. PATIENTS AND METHODS: From December 1989 to June 2001, 21 patients were treated for severe renal trauma. Up until 1995, all patients were operated urgently or on the 7th day (n = 12). After 1995, patients were operated (n = 3) or managed nonoperatively (n = 6). We retrospectively studied the age, gender, type of trauma (open, closed), associated lesions, radiological assessment performed, treatment and complications. RESULTS: 20 males and 1 female with a mean age of 30.3 years were managed for severe renal trauma (17 stage 3 and 4 stage 4; 20 cases of closed trauma, 1 case of open trauma). The radiological assessment comprised ultrasound (13 cases), abdominopelvic CT (19 cases) and IVU (4 cases). Thirteen patients presented with multiple injuries with associated visceral (8 cases), bone (7 cases), or mixed (3 cases) lesions. Six patients were managed nonoperatively and 15 patients were operated: 6 urgently (4 total nephrectomies), 9 on the average of the 7th day (conservative treatment). Five patients developed long-term complications (4 cases of renal atrophy, 1 urohaematic pseudocyst). The median follow-up was 13.5 months. CONCLUSION: The current approach to stage 3 renal trauma tends to be surveillance and nonsurgical management (carefully selected, haemodynamically stable patients). Vascular repair before the 5th hour is recommended for stage 4 trauma. Cases of delayed diagnosis of arterial thromboses are monitored.

[Tumor of the juxtaglomerular apparatus]. / Tumeur de l'appareil juxtaglomérulaire.

Renin-secreting tumours are rare tumours. The authors report a case of renin-secreting tumour discovered during investigation of HT associated with hypokalaemia and secondary hyperaldosteronism and recall the main clinical, laboratory, and radiological characteristics of this tumour, as well as its treatment.

Targeted therapies in non-muscle-invasive bladder cancer according to the signaling pathways.

With 300,000 annually new cases worldwide, urothelial-cell carcinoma of the bladder (UCCB) is the second most common urologic neoplasm after prostate carcinoma. Non-muscle-invasive bladder cancer (NMIBC), which is not immediately life-threatening, represents 70% to 80% of these initial cases. Despite optimal treatment (transurethral resection with intravesical chemo- or immunotherapy), 70% of these NMIBC will recur, and 10% to 20% will progress, highlighting the need for a new therapeutic approach. Indeed, the identification of patients at high risk of disease recurrence and progression would be beneficial in predicting which patients with NMIBC would benefit from strict follow-up and which would benefit from a more aggressive therapy. To date, conventional treatment remains disappointing in terms of oncologic results and morbidity. The growing understanding in tumor biology has enabled the signaling pathways involved in bladder tumorigenesis and progression to be identified, but few molecular targets have been available until now. The encouraging results seen in various human carcinomas suggests that these new agents should become part of the arsenal of drugs available in the treatment of NMIBC, alone or in combination with already known agents. In this article, we have tried to highlight the main molecular signaling pathways involved in NMIBC tumorigenesis and progression, and the potential targets useful for improving the treatment of NMIBC.