How to improve outcomes in Muscle Invasive Bladder Cancer
Muscle invasive bladder cancer is a complex disease that requires aggressive treatments. Due to the aggressive nature of the disease, timely diagnosis and prompt treatment is required. However, nearly 50% of bladder cancer patients die despite aggressive surgery. Prof Hein Van Poppel, Adjunct Secretary General – Education, European Association of Urology, addresses ways to improve outcomes.
In the last 30 years, we have not been able to improve the survival rates of our muscle invasive bladder cancer patients. Although we have better surgical and anesthesiological tools, and that there was a dramatic decrease in mortality of cystectomy, bladder cancer continues to kill and about 50% of patients die from the disease despite aggressive surgery. The success of cystectomy in bringing cure depends on the timely indication.
Once invasive bladder cancer cannot be controlled with BCG and once the tumor has invaded the muscular layer, a cystectomy should be proposed and conservative measures are not allowed when the patient is fit for surgery. The cure rates are indeed significantly better in organ confined disease compared to extravesical extension and lymph node invasion. (1) Moreover, unlike in prostate cancer for instance, surgery is relatively urgent since postponing surgery more than 3 months from the diagnosis of muscle invasion has a significantly worse outcome. (2)
Although bladder sparing approaches (transurethral resection, systemic chemotherapy and radiotherapy) can obtain good results in selected patients, a Cochrane database analysis of individual trials shows a benefit of radical surgery over radiation. (3) In the male bladder, extirpation means a radical cystoprostatectomy with eventually simultaneous urethrectomy when the prostatic urethra is invaded. In the female, it equals an anterior exenteration with hysterectomy, ovariectomy, anterior colpectomy and cystourethrectomy.
Obviously, a cystectomy must achieve negative surgical margins since positive surgical margins decrease the 5 year cancer specific survival from 69 to 26.4 %. Performance of minimal invasive techniques (laparoscopic and robot assisted cystectomy) are therefore not the optimal approach for advanced bladder cancer. (4) Moreover, it has become clear from multiple studies that an extended lymph node dissection should accompany the cystectomy. Probably the lymph node clearing should encompass the external and internal iliac vessels, the obturator fossa and the common iliac artery up to the ureteral crossing. (5) A super extended lymphadenectomy up to the aorta and vena cava did not provide a benefit versus the extended dissection (6).
Since the publication of the neo-adjuvant chemotherapy studies, it has become clear that this treatment strategy before cystectomy improves the 10 year survival by nearly 6% (7) and therefore it is actually mentioned in the EAU Guidelines on Muscle Invasive Bladder Cancer that neo-adjuvant cisplatin containing combination chemotherapy should be offered in muscle invasive bladder cancer irrespective of further treatment. It is obviously not recommended in patients with a poor performance status or impaired renal function. (8)
Also adjuvant chemotherapy, analysed in a meta-analysis showed a survival advantage (Advanced Bladder Cancer Analysis Collaboration) (9). A recent analysis of an international intergroup randomised phase III trial comparing immediate versus deferred chemotherapy after cystectomy in pT3, pT4 and/or N+ bladder cancer showed a significant improvement in progression free survival, most obvious in node negative patients (10). It is likely that the EAU Guidelines about adjuvant chemotherapy will need to be updated since this recent data.
The last important point is to concentrate the cystectomies in high volume centers. As shown by Barbieri et al, (11) there is a significant reduced mortality in centers that perform more than 60 cystectomies per year. Another study showed that a number of annual procedures favors high volume versus low volume centers. (12)
In conclusion, radical cystectomy with extended pelvic lymph node dissection is the treatment of choice for muscle invasive bladder cancer. Cure implies timely indication for muscle invasive bladder cancer. Cure implies timely indication in performance of cystectomy while bladder sparing and less aggressive approaches must be carefully selected. It is likely that more cisplatin based chemotherapy will ultimately make the difference and this needs a mind change in the urological community and finally surgery is best done in experienced high volume centers
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2. RF Sanchez – Ortiz, WC Huang, R Mick et al. An interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma. J Urol 2003; 169: 110-115.
3. M Shelley. Surgery versus radiotherapy for transitional cell carcinoma. Cochrane database systematic reviews 2002
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13. LS Elting, C Pettaway, BN Bekele et al. Correlation between annual volume of cystectomy, professional staffing, and outcomes: a statewide, population based study. Cancer 2005; 104: 975-984.