Treatment of Bacillus Calmette-Guerin refractory superficial bladder cancer: further intravesical therapy

We here report our clinical experience with salvage therapy for patients with bacillus Calmette-Guerin (BCG)-refractory superficial bladder cancer and discuss current approaches to the disease, especially focusing on bladder preservation. First, we evaluated the efficacy of an initial 6-week course of intravesical BCG in 93 patients with carcinoma in situ (CIS) of the bladder. Of these, 91% achieved a complete response (CR) at the evaluation at 3 months. The 2- and 5-year recurrence-free rates were 71 and 67%, respectively (mean follow-up 39 months). These results support the intravesical BCG as a first-line therapy for CIS. Next, we assessed the efficacy of a second course of intravesical BCG for 16 patients who failed the initial induction course for CIS. Of these, 94% achieved CR at the evaluation at 3-month, and the 2- and 5-year recurrence-free rates were 62 and 46%, respectively (mean follow-up 28 months). None of the patients who received a second course had disease progression. Thus, a second course of BCG therapy seems to be a reasonable option for CIS patients failing the initial course. We also report our initial experience with intravesical gemcitabine therapy for 3 patients with BCG-refractory CIS of the bladder and 1 patient with recurrent multiple tumors. Gemcitabine (1500 mg in 100 ml saline) was given in the bladder for 1 hour twice weekly for a total of 12 treatments. The treatment was associated with minimal bladder irritation and systemic absorption, and was well tolerated except in a 90-year-old man who discontinued therapy because of grade 2 toxicity. Two patients achieved CR and maintained a tumor-free status beyond 14 months, suggesting that the intravesical gemcitabine is a promising salvage therapy for BCG-refractory superficial bladder cancer.     

State-of-the-art management of metastatic disease at initial presentation or recurrence

Carcinoma of the bladder is the second most prevalent genitourinay malignancy and the fifth most common solid tumor in the USA. On the basis of favorable response rates and survival data, cisplatin-based regimens can be considered the standard treatment for fit patients with metastatic urothelial cancer. Since cisplatin-containing regimens are contraindicated for patients with impaired renal function, gemcitabine plus either paclitaxel or docetaxel may be an effective and well-tolerated treatment option for these patients. Randomized trials are needed to determine the future role of these combinations in the management of advanced transitional cell carcinoma. The optimal regimens for the medically unfit patients and second-line chemotherapy remain undefined. Postchemotherapy surgical resection of residual cancer may result in a disease-free survival in highly selected patients who would otherwise die of the disease. Progresses in the understanding of the molecular biology of bladder cancer and identification of new targeted therapies will undoubtedly provide new opportunities but whether or not this approach to therapy will lead to better results must still be determined.     

Five-year survival results of subcutaneous low-dose immunotherapy with interleukin-2 alone in metastatic renal cell cancer patients

After the discovery of its essential role in anticancer immunity, IL-2 cancer immunotherapy has shown that comparable results may be obtained with different schedules, including intravenous high-dose IL-2 as a bolus or as a 24-hour intravenous infusion or prolonged subcutaneous injection of low-dose IL-2 with or without IFN-alpha. This study shows the long-term results obtained in 92 metastatic renal cell cancer (RCC) patients with low-dose subcutaneous IL-2, which was given at 3 million IU twice/day for 5 days/week for 6 consecutive weeks. In nonprogressing patients, a second cycle was planned after a 21-day rest period, followed by maintenance therapy consisting of 5 days of treatment every month until disease progression. Complete response (CR) was achieved in only 2/92 (2%) patients, and partial response (PR) was observed in 19 patients (21%). Therefore, the response rate (CR + PR) was 21/92 (23%), with a median duration of response of 25 months. Stable disease (SD) occurred in 37 patients (40%), whereas the other 34 (37%) had a progressive disease (PD). The response rate was significantly higher in patients with a disease-free interval of >1 year than in those with a lower interval, in patients with a high performance status (PS) than in those with a low PS, and in patients with sites of disease other than the liver. A 5-year survival was obtained in 9/92 (9%) patients, and the percent of survival was significantly higher in patients with a response or SD than in those with PD. The treatment was well tolerated in all patients. This study confirms that low-dose subcutaneous IL-2 alone in an effective and well tolerated therapy of metastatic RCC, with results comparable to those described with more aggressive and toxic IL-2 schedules.     

A prospective, open label, randomized phase II trial of weekly docetaxel versus weekly vinorelbine as first line chemotherapy in patients with androgen independent prostate cancer

PURPOSE: In previous phase I to III studies docetaxel and vinorelbine have shown promising activity in androgen independent prostate cancer. In the present trial we assessed the efficacy and tolerability of single agent low dose docetaxel vs vinorelbine in patients with advanced androgen independent prostate cancer. MATERIALS AND METHODS: A total of 40 chemotherapy naive patients with histologically proven androgen independent prostate cancer, adequate androgen ablation, and clinical and/or biochemical progression were randomly assigned to receive either 25 mg/m(2) docetaxel (arm A) or 25 mg/m(2) vinorelbine (arm B) weekly. Treatment was continued until clinical and/or biochemical progression. In cases of progression patients switched to the alternative treatment arm. The primary end point was time to disease progression. Secondary end points included prostate specific antigen response rates in sequential treatment, analgesic response and toxicity. RESULTS: The current analysis showed a doubled risk of progression in treatment arm B. The median time to first disease progression was 14.5 months for arm A vs 4.4 months for arm B. The proportion of patients with a greater than 50% prostate specific antigen decrease on first line therapy was significantly higher in arm A (62.5%) compared to arm B (11.1%) (p = 0.0033). After progression to docetaxel second line vinorelbine yielded a greater than 50% prostate specific antigen response rate of 28.6% vs 62.5% for second line docetaxel. Clinically significant toxicity occurred more often in arm B with neutropenia grade 4 seen in 22% and grade 3 in 28% of patients (p = 0.0005) during the first treatment phase. CONCLUSIONS: While weekly application of both cytotoxic agents was well tolerated, this study demonstrates the superiority of docetaxel vs vinorelbine as monotherapy in the treatment of androgen independent prostate cancer.     

Combination chemotherapy with bleomycin, vinca alkaloid and cisplatin (BVP) for advanced urothelial cancer

Since October 1979, 18 patients with metastatic urothelial cancer have been treated with combination chemotherapy of bleomycin (5-10 mg/day administered on days 1 to 7), vinca alkaloid (vinblastine 5-10 mg/day or vincristine 1 mg/sqm on days 8 and 9) and CDDP (60 mg/sqm on day 10). CR was achieved in 3 of the 18 patients and PR in 6 patients. Over-all, the response rate was 50%. Among 3 patients who achieved CR, 2 patients are still free of disease for 31 months and for 28 months, and the other is alive with cancer for 26 months. The 2-year survival rate was 58% in responders (CR + PR) and 0% in nonresponders. (p less than 0.005). In many cases, the response was observed after the first or second course of BVP therapy, and there was a relatively good response in patients with lymphnode metastasis alone. The treatment was tolerated well and common toxic effects were nausea, vomiting of moderate to severe degree (100%), myelosuppression (50%) and mild nephrotoxicity (22%). As to the choice of vinca alkaloids, vincristine seemed to be the treatment of choice because it was less toxic than vinblastine and was almost equally effective.     

Gemcitabine and vinorelbine combination in patients with metastatic breast cancer

Both gemcitabine and vinorelbine as single agents have significant activity against metastatic breast cancer, with an overall response rate ranging from 14% to 40%. Because each drug has different mechanisms of action and toxicity profile, we have evaluated the activity and tolerability as a combined regimen in metastatic breast cancer patients. Thirty-two breast cancer patients with prior chemotherapy for metastatic disease received a combination of gemcitabine and vinorelbine at 1,200 and 30 mg/m ², respectively. The drugs were administered on days 1 and 8 of every 21-day cycle. The study was designed to evaluate the response rate, the duration of response, the time to progression, and overall survival. Toxicity and tolerability of this combination were also evaluated. Out of 32 patients analyzed, a complete response was achieved in 2 patients (6.3%) and a partial response in 12 patients (37.5%), with an overall response rate of 43.8%. After a median follow-up of 7 months, the median duration of response was 5.3 months, and the time to progression was 5.0 months. Overall survival was not reached because the majority of the patients were alive at the time of analysis. The gemcitabine and vinorelbine combination was tolerable, with hematologic toxicity being the most common side-effect. Three patients suffered from grade 4 neutropenia, and none suffered from grade 4 thrombocytopenia. Nonhematologic toxicity was minimal and transient, with nausea and phlebitis being the most common. The gemcitabine and vinorelbine combination at the previously specified doses shows significant activity in metastatic breast cancer patients. The treatment is well tolerated and has an acceptable toxicity profile. In patients previously treated with anthracyclines and taxanes, this combination regimen offers an alternative treatment with preservation of a good quality of life.     

Intravesical BCG in patients with carcinoma in situ of the urinary bladder: long-term results of EORTC GU Group phase II protocol 30861

OBJECTIVES: This phase II study was designed to assess the response rate, side effects and long-term efficacy of BCG in the treatment of carcinoma in situ (Cis) of the urinary bladder. METHODS: 103 eligible patients with Cis were treated with 6 consecutive weekly intravesical instillations of 120 mg BCG-Connaught. In case of no response, a second 6-week course was given. RESULTS: A complete response (CR) was observed in 77 of the 103 eligible patients (75%) and 93 evaluable patients (83%). In 6 of 10 patients the CR was induced by a second cycle of 6 weekly instillations. After a median follow-up of 7.6 years, 39 of the 77 CR patients (50%) are still alive and have retained their bladder, 31 (40%) without tumor recurrence. Another 7 patients underwent cystectomy and are still alive while 16 (20%) have died due to bladder cancer. Ten patients stopped treatment due to toxicity. In 2 patients, cystectomy was done because of severe cystitis and reduced bladder capacity. Drug cystitis, bacterial cystitis and fever occurred in 45, 15 and 15% of the patients, respectively. Severe drug cystitis was noted in 3 out of 10 patients receiving more than 6 instillations, necessitating cystectomy in 1 case. CONCLUSION: Intravesical short-term BCG is an effective treatment modality in Cis, yielding a high CR rate. This therapy may however be suboptimal in some patients as the 5-year disease-free rate in complete responders drops to 60%. Still, this is an acceptable result for patients in whom cystectomy would otherwise be performed in virtually all cases.     

Bladder cancer

Urothelial carcinoma of the bladder is the most common malignancy affecting the urinary tract. This review examines the current standards in the diagnosis and management of this disease. Cystoscopy and urine cytology remain important tools in the diagnosis and follow-up of bladder cancer. Alternatives include photodynamic diagnosis, narrow band imaging and professional image enhancement which may improve detection of tumours. En-bloc resection using either laser or electrocautery shows promise in improving the quality of transurethral resection. For patients with muscle-invasive bladder cancer, robot-assisted radical cystectomy has been shown to be oncologically equivalent to open radical cystectomy; however, cost effectiveness remains to be determined. The mainstay of bladder preservation treatment in muscle-invasive cancer is trimodal therapy utilizing transurethral resection and chemoradiotherapy with equivalent outcomes to radical cystectomy in selected patients. Management of locally advanced and metastatic disease has rapidly advanced through the use of systemic immunotherapy agents targeting the PD-L1/PD-1 axis.     

Efficacy of intravesical bacillus Calmette-Guerin for carcinoma in situ of bladder

Three months after an initial 6-week course ofintravesical bacillus Calmette-Guerin (BCG) given between January 1990 and March 2005, 94 (90%) out of 104 patients with carcinoma in situ (CIS) of the bladder achieved a complete response (CR). The 5- and 10-year recurrence-free rates were 67 and 60%, respectively (median follow-up 42 months). Three months after a second course ofintravesical BCG given to 23 patients who failed the initial induction course for CIS was evaluated. Of these, 96% achieved a CR, and the 5- and 10-year recurrence-free rates were 56 and 28%,respectively (median follow-up 23 months). Only one patient who received a second course of BCG therapy showed disease progression. Two of the 4 patients with BCG-refractory CIS of the bladder achieved CR after intravesical gemcitabine therapy and maintained a tumor-free status beyond 6 months. Five of the 16 patients showing disease progression had upper urinary tract cancer, 4 had recurrent or muscle invasive bladder cancer, 6 had prostatic involvement of CIS, and one patient had urethral recurrence. Three of the 16 patients died. Bladder preservation was achieved in 97 of the 104 patients, although 7 patients ultimately underwent radical cystectomy and urinary diversion for aggressive disease. In conclusion, some patients may be managed safely by repeated endoscopic resection and intravesical therapy with cystectomy postponed until objective evidence of progression exists.     

Current status of the conservative treatment of urinary bladder for invasive bladder cancer]

During the 3 years from 1987 to 1990, we gave hyperthermia to 11 of the patients who visited our department for the treatment of invasive bladder cancer. Results and prognosis are reported. Stage and grade of the cancer before the treatment in 11 cases were T2 in 5 cases, T3 in 3 cases, T4 in 3 cases, transitional cell carcinoma (TCC) grade 2 in 8 cases, TCC grade 3 in 2 cases, and TCC grade 3 + anaplastic carcinoma in 1 case. Complications were observed in 8 of the 11 cases, such as severe heart disease and others. Pretreatment of radiation therapy, transurethral resection or chemotherapy was given in all cases. Hyperthermia was performed combined with hydroxypropyl cellulose-(HPC)-adriamycin, or radiation therapy, and the following results were obtained: complete response (CR) in 4 cases, partial response (PR) in 4 cases, no change (NC) in 2 cases and progressive disease (PD) in 1 case. Among 4 cases of PR, total cystectomy was performed in 3 cases. These 3 cases and the 4 cases of CR are alive now, but the other 4 patients died.     

Results of Medical Research Council phase II study of low dose cisplatin and methotrexate in the primary treatment of locally advanced (T3 and T4) transitional cell carcinoma of the bladder

A series of 49 previously untreated patients with category T3 or T4 bladder cancer underwent treatment with low dose methotrexate and cisplatin; 44 patients were eligible for assessment of response. Complete response (CR) was seen in 5 patients (11%) and partial response in 15 (34%) (overall response rate 45%). Treatment was reasonably well tolerated with no major morbidity and no treatment-related deaths. After a median follow-up of 3.5 years, the 1-year and 2-year survival rates were 70 and 30% respectively. Ten patients remain recurrence-free without having received "definitive local therapy" (cystectomy and/or radiotherapy) at follow-up extending from 20 to 50 months.     

Preliminary results of concurrent cisplatin and radiation therapy in locally advanced bladder cancer.

Between March 1981 and March 1990, 15 patients with locally advanced transitional cell carcinoma of the bladder were treated concurrently with cisplatin and radiotherapy. Treatment comprised a radiation dose of 40-50 Gy in 20-25 fractions over 4-5 weeks and intravenous infusion of cisplatin with hydration during days 1-5 and 22-26. The total scheduled dose of cisplatin was 200 mg. A complete response (CR) was seen in 3 patients (2 T2 tumours and 1 T3) and the other 12 were regarded as partial responders. Two of the 12 partial responders (1 T2 tumour and 1 T4) underwent cystectomy after treatment, but 9 patients (2 T2, 6 T3 and 1 T4) underwent only transurethral resection. The remaining patient (with a T4 tumour) died from systemic disease, further treatment not being possible because of unrelated heart failure. In 3 CR patients and 9 with a partial response (PR), bladder function was preserved and they have survived for a mean of 18.3 months (range 5-47) after therapy. Although 4 patients in this group had recurrent bladder tumours and 1 died from cancer in another part of the body, 7 have survived with normal bladder function and no recurrence. It is concluded that concurrent cisplatin and radiation therapy is a safe and viable regimen and may be considered as a means of preserving the bladder in patients with locally advanced transitional cell carcinoma.     

Phase II study of carboplatin in locally advanced and metastatic transitional cell carcinoma of the urinary bladder

Twenty-five previously untreated patients with measurable locally advanced and/or metastatic transitional cell carcinoma of the urinary bladder were included in a phase II study with carboplatin. Bolus injections were administered in 2 courses every 4 weeks at an initial dose of 400 to 450 mg/m2 with the option of increasing the dose to 450 to 500 mg/m2 in individual patients during the second cycle, depending on haematological toxicity. Two patients had a complete response (CR), 13 showed no change (NC) and 9 had progression of disease (PD), including 4 early progressions. There was no delay in treatment because of myelosuppression. Thrombocytopenia led to a reduction in drug dosage. No reduction in renal function was observed. Increased dosage did not increase the response rate. This study indicated the low effectiveness of single agent carboplatin in transitional cell carcinoma of the urinary bladder.     

Quadruple primary urogenital cancers – A case report

IntroductionUrogenital cancers are not an uncommon occurrence in daily practice. Prostate cancer is the second most frequent cancer in men, kidney cancer accounts for 2.4% of all cancers and bladder cancers represent 3.1% of cancers in both men and women [1]. However, the cases of a simultaneous development of all three cancers, including one with a neuroendocrine component, are very few and far between.Presentation of caseOur case report involves a case of a patient with prostate adenocarcinoma, clear-cell renal carcinoma, papillary renal carcinoma and small-cell bladder cancer. The patient was treated as if he had separate pathologies by a multidisciplinary team: surgical and oncological, performing radical cystoprostatectomy with left perifascial nephroureterectomy, right ureterostomy and adjuvant chemotherapy, with excellent outcome even four years after the initial diagnosis.DiscussionThe distinct features of this case are the occurence of four different malignancies of the urogenital system, the family history of colon cancer, the development of small-cell carcinoma of the bladder, which is extremely rare and the good outcome, despite the quadruple malignancies and the aggresivity of the small-cell carcinoma.ConclusionMutiple primary malignancies are a relatively rare pathology, but should be considered as a possibility in patients who already had a second malignancy. Cases of patients with MPMs should be supervised by a multidisciplinary team and should be followed closely.     

Capecitabine and Vinorelbine as an All-Oral Chemotherapy in HER2-Negative Locally Advanced and Metastatic Breast Cancer

BACKGROUND: The oral formulation of vinorelbine together with capecitabine allows for an all-oral combination chemotherapy which promises to raise quality of life of patients with advanced breast cancer. PATIENTS AND METHODS: Patients with HER2-negative, locally advanced, inoperable or metastatic breast cancer were included in this prospective observational trial (treatment schedule: capecitabine 500 mg/m2 twice daily, days 1-14; vinorelbine 60 mg/m2, days 1+8; repeated in 3-week cycles). RESULTS: All 32 patients (median age 50 years) were evaluable for toxicity, and 30 patients for response. Twentyfour patients received therapy as first-line treatment, and 8 patients as beyond first-line treatment. Median time to progression was 8 months, and median overall survival was 32 months. Complete response was observed in 1 patient (3%), partial response in 10 patients (33%), and disease stabilization for more than 6 months (SD > 6) in 10 patients (33%). This results in an overall response rate (ORR) of 37% and a clinical benefit rate (ORR + SD > 6) of 70%. The only grade 3/4 toxicities were neutropenia (19%) and hand-foot syndrome (9%). CONCLUSIONS: The all-oral combination of capecitabine/vinorelbine at this schedule appears to be an effective, well-tolerated regimen for treatment of advanced breast cancer, and offers a promising alternative to single-agent capecitabine and vinorelbine as well as intravenous polychemotherapy.     

The fate of the bladder in patients with metastatic bladder cancer treated with cisplatin, methotrexate and vinblastine: a Northern California Oncology Group study

We report the efficacy and toxicity of combined cisplatin, methotrexate and vinblastine for the treatment of metastatic transitional cell carcinoma of the bladder in 50 evaluable patients. Of these 50 patients 17 had not undergone cystectomy and had residual invasive bladder cancer. Of these 17 patients 11 had complete response of the bladder lesions following cisplatin, methotrexate and vinblastine for metastatic disease, including 6 of 12 treated by cisplatin, methotrexate and vinblastine alone, and 5 of 5 treated with cisplatin, methotrexate and vinblastine plus palliative or preoperative pelvic irradiation. Complete response was confirmed in 10 of the 11 patients by endoscopy and biopsy, and in 1 by cystectomy. One patient whose liver metastasis responded to cisplatin, methotrexate and vinblastine had conversion to complete response by cystectomy for persistent bladder cancer. Of these 17 patients 7 are alive, including 5 without disease, 4 to 41 months after treatment. The bladder appears to be responsive to this combination chemotherapy for invasive transitional cell carcinoma. This experience underscores the need for regular pathological re-staging of the bladder cancer in patients receiving chemotherapy.     

Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group

PURPOSE: We assess the efficacy and safety of intravesical valrubicin for the treatment of carcinoma in situ in patients with failure or recurrence after bacillus Calmette-Guerin (BCG) and who otherwise would have undergone cystectomy. Total anthracycline recovery in urine samples obtained within 24 hours of valrubicin administration was assessed in a subset of patients. MATERIALS AND METHODS: A total of 90 patients with recurrent carcinoma in situ after failed multiple prior courses of intravesical therapy, including at least 1 course of BCG, participated in this open label, noncomparative study. Each patient received 6 weekly instillations of 800 mg. intravesical valrubicin. Disease evaluations were made at baseline and 3-month intervals following treatment. Evaluations included cystoscopy with biopsy and urine cytology. Toxicity was noted throughout treatment and followup. No evidence of disease recurrence for 6 months or greater was considered a complete response. RESULTS: Of 90 patients 19 (21%) had a complete response, including 7 who remained disease-free at the last evaluation, with a median followup of 30 months. Additionally, 14 patients who did not meet the strict protocol definition of complete response had superficial Ta disease only. Median time to failure and/or last followup for complete responders was greater than 18 months. Recurrence has been noted in 79 patients to date, including only 2 with clinically advanced disease (stage T2). Of these 79 patients 44 (56%, 4 responders and 40 nonresponders) underwent radical cystectomy. Of the 41 patients with known pathological stage 6 (15%) had stage pT3 or greater at cystectomy. Four patients died of bladder cancer during the median followup of 30 months, none of whom was a complete responder or underwent cystectomy following valrubicin. The main side effects of valrubicin therapy were reversible local bladder symptoms. CONCLUSIONS: Valrubicin was effective and well tolerated in patients with carcinoma in situ of the bladder refractory to BCG therapy. Delaying cystectomy while attempting salvage therapy with valrubicin does not pose an undue risk to most patients.     

Cyclic interferon gamma treatment of patients with metastatic renal carcinoma

The treatment of metastatic renal carcinoma is still unsatisfactory because of the lack of effective systemic therapy. In 14 patients with metastatic renal carcinoma an attempt was made to influence the course of the disease by administration of recombinant human interferon (rHu-IFN) gamma; 9 patients were evaluated after treatment. There was partial remission in 3 patients, stable disease in 2 and tumour progression in 4. The cyclic application of rHu-IFN at a dose of 0.25 mg/day for 8 days, with treatment-free intervals of 3 to 4 weeks, was tolerated well. Side effects consisted mainly of fever and leucocytopenia. From this small series it seems that cyclic IFN gamma treatment might be helpful in some cases of metastatic renal carcinoma.     

Systemic therapy issues: Immunotherapy in nonmetastatic urothelial cancer

Non–muscle-invasive bladder cancer is one of the most common malignancies. Patients with intermediate-risk or high-risk disease can be treated with intravesical Bacillus Calmette-Guerin, a vaccine against tuberculosis. However, many of these patients will experience tumor recurrence, despite appropriate treatment. 1 The standard of care in these patients is radical cystectomy (RC) with urinary diversion. 2 Patients diagnosed with muscle-invasive bladder cancer (MIBC) have traditionally faced 2 main treatment options: RC and urinary diversion, as in Bacillus Calmette-Guerin-unresponsive Non–muscle-invasive bladder cancer, or alternatively, trimodal therapy comprising maximal transurethral resection of bladder tumor plus chemoradiation. 3 For patients with MIBC and clinical (c)T2–T4a, neoadjuvant chemotherapy (NAC) preceding RC is supported by Level 1 evidence with a modest 5-year overall survival benefit of 5% with cisplatin-based regimens. 4–9 A number of factors preclude MIBC patients from standard treatment options. For example, patients with serious comorbidities might be unable to tolerate general anesthesia, while others might be unwilling to adapt to the lifestyle changes after RC. 10-12 Likewise, patients with extensive carcinoma in situ or poor bladder function might not be optimal candidates for trimodal therapy or be prepared for the ongoing risk that salvage RC might be ultimately required. Reasons for the underuse of NAC range from the fear of delaying potentially curative surgery in nonresponders to patient ineligibility to cisplatin-based NAC. 13,14 Despite best efforts, in both surgical and bladder-sparing approaches, the 5-year overall survival in treated patients with MIBC is only 35% to 50%. 3,15 Strategies to improve overall prognosis as well as to reduce the indications of RC are desperately needed. Trial results have demonstrated the unprecedented ability of immune-checkpoint inhibitors to induce durable remissions in some patients with metastatic urothelial carcinoma. 16-20 Furthermore, immune-checkpoint inhibitors have shown to be better tolerated than traditional chemotherapy. 16 These successful results have spearheaded the research on these agents in earlier curative settings, with the shared goal of improving overall outcomes, and potentially avoid surgery in patients who show complete response (pT0). Strategies to enhance the immune response by combining immunotherapy with immune sensitizers such as chemotherapy, immunotherapy, targeted therapy or radiation are on the rise.     

Brain metastases from transitional cell carcinoma of the bladder

We present our experience with 4 patients with transitional cell carcinoma of the bladder and brain metastases. In all 4 cases a solitary intracranial metastasis occurred. In 3 patients this represented the first site of recurrent disease following systemic chemotherapy. Aggressive therapy of the brain metastases was instituted in 3 patients, including external beam radiation and in 2 cases surgical resection. Although all patients died only 3 died as a result of metastatic transitional cell carcinoma, including 2 who died as a direct result of intracranial disease. A review of the literature suggests an increasing incidence of brain metastases from transitional cell carcinoma of the bladder with the advent of more aggressive therapy for bladder cancer, which includes radical surgery for high stage disease and combination chemotherapy. Aggressive intervention for solitary brain metastases from transitional cell carcinoma can relieve neurological dysfunction and may prolong survival.