Radical cystectomy in regionally advanced bladder cancer.

The distinction pathologically of invasive tumors confined to the muscularis propria from those that penetrate the bladder wall and invade the perivesical fat or adjacent organs is a critical prognostic determinant. Nodal metastases are evident in approximately one half of patients with tumors pathologically staged as P3b or greater. Five-year survival rates after radical cystectomy with or without preoperative irradiation for stage P3b tumors range from 17% to 46%. Long-term survival is the exception when bladder cancer invades the pelvic sidewall or adjacent structures, yet cystectomy can provide palliation and accurate staging and can be considered in the context of combination therapy. Supravesical diversion can provide palliation when there is nodal disease above the bifurcation or pelvic fixation. The optimal role of adjuvant chemotherapy in the treatment of regionally advanced bladder cancer is yet to be defined. Tannock has delineated the many serious pitfalls inherent in interpreting nonrandomized trials of new therapies (see also his article elsewhere in this issue). Randomized trials are currently under way to determine if survival can be improved with adjuvant or neoadjuvant chemotherapy and the most efficacious timing of chemotherapy administration. Clinicians should generally resist the tendency to treat all patients with these regimens until it is clear that we are truly improving the outcome of therapy and the quality of life for our patients.     

Transurethral resection in regionally advanced bladder cancer.

Various treatments have proved useful for disease control in some patients with regionally advanced bladder cancer. Transurethral resection may cure some patients with invasive disease, but identifying patients with such potential early in their course is difficult. A restaging transurethral resection helps indicate whether conservative management is feasible and, if not, which operation is appropriate. In some patients, transurethral resection may enhance the response to chemotherapy. Research is needed to identify those tumor characteristics associated with good results of conservative management of regionally advanced bladder cancer.     

Radiation therapy in regionally advanced bladder cancer.

In conclusion, for patients undergoing bladder preservation, conventional external radiation therapy can no longer be recommended as a curative single modality. The usefulness of prognostic indicators, such as radiation responsiveness and tumor morphology, will have to be evaluated in light of newer treatment regimens. Patients should receive external radiation only if other therapies such as hyperfractionation, brachytherapy, intraoperative electrons, or combined chemotherapy and radiation therapy are unavailable or unable to be tolerated. Patients undergoing a planned cystectomy should receive preoperative radiation therapy until such time as neoadjuvant chemotherapy has been proved more or equally effective.     

Treatment of regionally advanced bladder cancer. An overview.

The finding of muscle-infiltrative bladder cancer is generally considered ominous, as 50% of patients who present with this condition are likely to develop distant metastases within 2 years. However, some types of infiltrative bladder cancer appear to have a less ominous prognosis. In order to assess the results of various therapies on regionally advanced bladder cancer, it is important to characterize the distinctions between the types with a poor prognosis (5-year survival rate 15% to 30%) and those with a better prognosis (5-year survival rate 50% to 85%). The former have a nodular architecture, infiltrate more deeply and in a tentacular pattern, and more often involve the bladder wall vasculature and lymphatics than does the latter type, which has papillary architecture and infiltrates on a broad front. These two types appear to respond differently to various treatments except systemic chemotherapy.     

Systemic chemotherapy in regionally advanced bladder cancer. Theoretical considerations and results.

Integrating systemic chemotherapy into the treatment of patients with invasive bladder cancer, where the majority of deaths are from systemic relapse, is crucial if survival is to be improved. However, the global recommendation of a single treatment approach for all patients is becoming outdated as several groups have found that appropriately selected patients enjoy comparable survival whether treated by transurethral resection alone or by partial or radical cystectomy. Thus, refining case selection becomes a critical area of investigation. Patients with a high risk of systemic relapse should be considered for systemic therapy early in the course of the disease, ideally as part of a clinical trial. The availability of growth factors has reduced the toxicities of the regimens currently in use. Improvements in assessing biologic potential are required, so that treatment recommendations will allow patients the maximal chance of cure and maintenance of organ function, while minimizing toxicities in patients for whom systemic approaches are unwarranted. Of interest are recent reports that G-CSF may enhance tumor sensitivity to methotrexate in vitro and increase the sensitivity of implanted urothelial tumors to chemotherapy in nude mice. Such findings suggest an expanded role for these agents. Unfortunately, simple escalation of all components of a combination regimen does not appear to be a viable strategy, as it is unlikely to significantly increase CR proportions without prohibitive toxicities. However, as more is understood about drug resistance, and in particular its development in vivo, better sequencing of the available of options should be possible. The availability of effective salvage therapies suggests that this is an appropriate therapeutic approach. In addition, a number of strategies aimed at reversing the mdr phenotype are under study. These include calcium channel blockers such as verapamil, cyclosporin, and tamoxifen. Alternatively, some groups are investigating transfecting the mdr gene into bone marrow cells to reduce the sensitivity of these cells to cytotoxic agents. These novel designs can be tested both in patients with metastatic disease and in patients with locally advanced (T3b, T4, and N+) disease, who have a high risk of metastatic failure and low CR proportions to available regimens.     

M-VAC versus CisCA--chemotherapy in the treatment of advanced bladder cancer.

The results of this study do not demonstrate a superiority of M-VAC chemotherapy over a modified CisCA regimen chemotherapy. M-VAC, however, proved less toxic than CisCA in terms of side effects. Neither CisCA nor M-VAC was effective as a curative treatment for patients with distant metastases. A durable complete remission of 22.5 months was seen in only 2 of the 12 patients with locally advanced tumors without distant metastases treated with M-VAC, and one of 35 months was observed in only 1 of the 6 cases with locally advanced tumors treated with CisCA chemotherapy.     

A clinical survey of advanced bladder cancer: treatment of advanced and non-resectable bladder cancer]

Sixty-three patients with advanced cancer of more than T3b and/or non-resectable bladder cancer who were treated at Kanazawa University Hospital from January 1982 to June 1990 were analyzed with regard to treatment and prognosis. Thirty-one of the 63 patients had non-resectable bladder cancer; T3b in 9, T4b in 15, M1 in 6 and N4 in 4. Twenty-four of the 31 patients received anticancer therapy consisting of systemic chemotherapy, 8 MHz-RF hyperthermia, radiation or a combination of these modalities. With this treatment 9 patients achieved partial response, 4 minor response, 7 no change and 2 progressive disease. In 2 patients evaluation was not performed. Seven of the 31 patients received no treatment. One-year and 2-year survival rates with the above types of treatment were 27.7% and 16.7%, respectively, and 33.4% and 16.7%, respectively, without anti-cancer treatment. There was no significant difference between the survival rates of the two groups. Thirty-two of the 63 patients underwent operation. In 17 patients, total cystectomy was carried out, 9 and 8 of whom received and did not received respectively various adjuvant therapies before operation. One-year and 2-year survivals in the group undergoing adjuvant therapy were 33.3% and 11.1%, respectively, and 66.7% and 66.7% respectively in the group without adjuvant therapy. Survival of the 2 groups did not differ significantly. These data indicate that anticancer treatment including chemotherapy, hyperthermia and radiation dose not enhance long-term survival.     

Recent developments in the treatment of advanced bladder cancer

Urothelial carcinoma of the bladder is a common malignancy which has historically been difficult to treat in its advanced stages. Clinically effective treatment options for locally advanced/inoperable or metastatic urothelial carcinoma (mUC) consisted of cisplatin-based chemotherapy regimens, with few other impactful therapeutic options. The past 2 years have seen a remarkable shift in the therapeutic landscape of mUC, with 5 novel immunotherapy agents receiving FDA approval for mUC, including first-line and second-line postplatinum settings. There are now many important clinical trials ongoing seeking to answer how best to use chemotherapy, immunotherapy, and targeted therapy agents in patients with mUC. Here we review the current standard of care for patients with mUC based on published data from the past 2 years, and look forward toward future research directions.     

Post-chemotherapy surgery in patients with unresectable or regionally metastatic bladder cancer

PURPOSE: We update our experience with post-chemotherapy surgery in patients with unresectable or lymph node positive bladder cancer. METHODS: Of 207 patients with unresectable or regionally metastatic bladder cancer 80 (39%) underwent post-chemotherapy surgery after treatment with a cisplatin based chemotherapy regimen. We assessed the impact of surgery on achieving a complete response to chemotherapy and on relapse-free survival. RESULTS: No viable cancer was present at post-chemotherapy surgery in 24 of the 80 cases (30%), pathologically confirming a complete response to chemotherapy. Of the 24 patients 14 (58%) survived 9 months to 5 years. Residual viable cancer was completely resected in 49 patients (61%), resulting in a complete response to chemotherapy plus surgery, and 20 (41%) survived. Post-chemotherapy surgery did not benefit those who failed to achieve a major complete or partial response to chemotherapy. Only 1 of the 12 patients (8%) who refused surgery remains alive. CONCLUSIONS: Post-chemotherapy surgical resection of residual cancer may result in disease-free survival in some patients who would otherwise die of disease. Optimal candidates include those in whom the pre-chemotherapy sites of disease are restricted to the bladder and pelvis or regional lymph nodes, and who have a major response to chemotherapy.     

Combined modality treatment with bladder preservation for muscle invasive bladder cancer

ObjectiveTo evaluate the 5-year results of the following trimodal therapy for treatment of some selected cases of muscle invasive bladder cancer.Materials and MethodsIn this prospective study, we included 104 patients with transitional cell carcinoma (TCC) (T2 and T3a, N0, M0) who were amenable to complete transurethral resection. All patients received adjuvant chemo-radiotherapy (CRT) in the form of gemcitabine and cisplatin and conventional radiotherapy after the maximum resection of their tumors. Two weeks later, all cases had radiologic and cystoscopic evaluation. The patients who showed no evidence of the bladder tumors [complete response (CR)] went on to complete the CRT, while those with recurrent invasive tumors did not receive any more CRT and were assigned to have salvage cystectomy. Thereafter, all patients were subjected to a regular follow-up.ResultsThis trimodal therapy was well tolerated in most of cases with no severe acute toxicities. Complete response was achieved in 78.8% of cases after the initial CRT, and tumor grade was found to be the most significant risk factor to predict this response (P = 0.004). With a median follow-up of 71 months for patients with initial CR, 16.2% of cases showed muscle invasive recurrences, and multifocality was the only significant risk factor for their development (P = 0.003). Meanwhile, superficial recurrences were detected in 8.1% of cases with initial CR and were successfully treated with transurethral resection and intravesical bacillus Calmette-Guerin (BCG). On the other hand, we reported distant metastasis in 24.3% of patients with initial CR, and tumor grade, stage and multifocality were the most significant risk factors for this complication (P = 0.002, 0.031, 0.006). No cases of contracted bladder or late gastrointestinal complications were demonstrated in this series. The 5-year overall survival rate for patients with initial CR was 67.6%, and for all the patients in this study it was 59.4%.ConclusionsThis trimodal therapy can be considered as a treatment option for patients with localized muscle invasive TCC. The best candidates for such therapy are those with solitary T2, low grade tumors that are amenable to complete transurethral resection.     

Systemic cisplatin-based chemotherapy in the treatment of advanced bladder cancer

Twenty one patients with advanced bladder cancer (metastases and/or loco-regional recurrences) were treated by cisplatin-based chemotherapy (cisplatin, adriamycin, cyclo-phosphamide (8 patients), cisplatin, methotrexate (8 patients) and cisplatin and radiotherapy (5 patients). The results with pure chemotherapy were, on the whole, disappointing, with a remission rate of 25% and a response rate of 50%. Only the combination of cisplatin-based chemotherapy and radiotherapy gave spectacular results with 50% complete response, but even then at the price of a high morbidity rate.     

Management of advanced bladder cancer in the elderly.

Patients over the age of 70 years will become an increasingly important component of uro-oncologic practice. Although few published studies have specifically addressed this population, it is clear that the elderly can expect outcomes similar to younger patients in the management of advanced bladder cancer provided care is taken in planning. Of particular importance is an understanding of the pathophysiology of aging, of the possible implications of the causative factors for bladder cancer, and of the potential impact of advanced age on the biology of urothelial malignancy. Future studies should specifically address the problems of older patients with this malignancy to ensure the optimal possible outcome and definition of the most appropriate balance of toxicity and efficacy.     

New approaches in the treatment of metastatic transitional-cell cancer of the bladder

Summary In recent years, chemotherapy of metastatic transitional-cell carcinoma of the bladder has advanced from the use of individual therapeutic agents, which has effected only rare responses, to the development of multi-agent regimens., which have greatly improved both partial and complete response rates, resulting in improved local care, palliation, and; perhaps, survival. However, because of the limited duration of response, frequent recurrences, and the significant proportion of patients with refractory disease, there have been only modest overall gains in long-term disease-free survival. These shortcomings have prompted investigation of alternative approaches to current combination chemotherapy regimens, including the use of hematopoietic growth factors and novel single-agent, multi-agent, and gene therapy protocols.     

应用联合脏器切除术治疗进展期胃癌的临床分析

目的：总结联合脏器切除术治疗进展期胃癌的经验。方法：对1994年8月至2001年11月施行联合脏器切除的137例进展期胃癌的临床资料进行回顾性分析。结果：联合肝切除11例，脾切除25例，横结肠切除13例，胆囊切除15例，副肾上腺切除4例，脾、胰体尾切除38例，胰十二指肠切除13例，其他手术18例。手术死亡率为0。随访1年、3年和5年生存率分别为60.2％、26.3％和16．6％。结论：严格选择手术适应证，联合切除受累脏器可提高胃癌的根治性和患者的生存率。