Dear Leigh,
I went and looked over the European guidelines, and they recommend limited lymph node dissection; in the USA there is a trend for removing extensive amounts but this approach has not been accepted in Europe at this time, and is still experimental in the US as well.
The EUA guidelines for post-op chemo in the adjuvant or metastatic setting are online, I excerpt some of it below. If you go and read the whole document, you'll be confronted with nasty sounding statistics so be sure you want to know before you look! But...since you live in the Netherlands it would be wise to understand the EORTC's point of view, and of course help you know what to ask your doctor, so have a look at the edited guidelines from 2004, I copy here:
9.4 Adjuvant chemotherapy
Several trials with combination chemotherapy appeared to show a difference in favour of chemotherapy. However, the results are controversial because of the small sample size and confusing analyses and methodology (11). Based on the desire to treat only patients who were truly at high risk, the EORTC together with several other international groups have begun a large adjuvant trial that will enlist 1,344 patients worldwide. The study will evaluate four cycles of immediate chemotherapy versus therapy at the time of relapse in high-risk patients with pT3-pT4 or node-positive disease. Three different chemotherapy regimens are permitted: MVAC, high-dose MVAC (HD-MVAC), and gemcitabine plus cisplatin (GC) (12-14).
Decisions concerning individual patients must be made after careful examination of the histological specimen and knowledge of the known relapse rates per pathological stage.
9.5 Metastatic disease
9.5.1 Chemotherapy protocols
Two prospective randomized trials have proven the superiority of MVAC (methotrexate, vinblastine, adriamycin and cisplatin) over single-agent chemotherapy (15,16).
The EORTC GU Group has compared a 2-weekly schedule of HD [high dose]-MVAC to standard MVAC (13). A statistically significant difference in terms of complete remission rate and progression-free survival in favour of HD-MVAC was observed. Although no difference in median survival was seen, an increase in 2-year survival
was observed. All the survival curves diverged in favour of the HD-MVAC treatment arm. However, this finding may have been due to the small number of patients in the tails of the curves.
Novel chemotherapeutic agents, such as gemcitabine and the taxanes, are among the most interesting therapeutic options currently available (17). In an international trial, MVAC was compared to GC (14). The overall survival rate was similar in both arms, as was time to progressive disease, time to treatment failure, and response rate. More GC patients than MVAC patients had grade 3/4 anaemia and hrombocytopenia. More MVAC patients than GC patients had grade 3/4 neutropenia, neutropenic fever, grade 3/4 mucositis and alopecia.
Quality of life was maintained during treatment in both arms. GC appeared to have a reduced toxicity profile compared to MVAC. This study was not statistically powered to reveal equivalence in terms of survival to MVAC, nor has GC been compared to HD-MVAC. Nonetheless, many clinicians have begun to use GC as another standard regimen.
The combination of gemcitabine and taxol has been shown to be highly effective in patients who have failed prior MVAC (18). When cisplatin, gemcitabine and taxol were given to untreated patients, high overall response rates were observed (19). The triplet is being compared to GC by the EORTC.
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phase III randomized trials are more reliable as they tend to stratify patients according to the number of risk factors to avoid imbalance in treatment arms.
More recently, significant interest has developed in molecular markers, such as p53, Rb and p21,to help optimize therapy and predict chemosensitivity (22).
9.5.3 Conclusions
Muscle-invasive bladder cancer can be treated with chemotherapy. Response to neo-adjuvant chemotherapy is an important prognostic factor, but this may represent patient selection factors. Whether it is best to give chemotherapy in the neo-adjuvant or adjuvant setting has not yet been clearly determined. Adjuvant studies in the literature have been less definitive than neo-adjuvant studies.
The ability to evaluate molecular prognostic markers such as p53 have led to new, adjuvant chemotherapy trials.
9.6 GUIDELINES ON CHEMOTHERAPY
• Cisplatin-containing combination chemotherapy has resulted in complete remissions in 40-70% of patients, with cures in selected cases
• MVAC and GC are both used as up-front chemotherapy for metastatic disease.
• A minimal survival benefit has been shown with neo-adjuvant chemotherapy before cystectomy or radiotherapy
• Neoadjuvant chemotherapy in combination with radiotherapy for the purpose of bladder preservation is an investigational approach
• Convincing data are not yet available on the benefits of adjuvant chemotherapy. Results of randomized adjuvant trials are pending
