Results of chemotherapy, new organ-preservation strategies comparable to cystectomy

By Dr. Maria De SantisThe final day of the congress featured a series of closing presentations. One of the most prominent lectures was on bladder-sparing treatment for localised disease. Here is an overview.

Radical cystectomy and lymphadenectomy is the gold standard for the treatment of muscle-invasive urothelial cancer (UC). Neither transurethral resection of the bladder (TURB) nor radiation alone provides adequate local control for unselected patients.

Recent organ-preservation strategies combining TURB, chemotherapy, and radiation (trimodality treatment) have shown local control and progression results comparable to cystectomy series. In very selected patients, invasive bladder cancers can be cured by TURB alone4 or neoadjuvant chemotherapy and TURB.

As a matter of principle, operable (neoadjuvant approach), as well as unresectable primary tumours are expected to respond to systemic chemotherapy. However, chemotherapy alone rarely produces durable complete responses of the bladder primary tumours. Downstaging with 2-3 cycles of MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) or CMV (cisplatin, methotrexate, and vinblastine) might be one benefit. Pathological complete responses of bladder primary tumours were reached in 12-50% of patients after MVAC and in 12-22% of patients after gemcitabine/cisplatin (GC). In more contemporary series with GC followed by radical cystectomy, the pT0 rates were disappointingly low, which may have been related to a lack of dose density and inappropriate delay of surgery.

Patients who refused cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer had a 64% rate of relapses in the bladder with an additional mortality of 30%.

Such patients might jeopardise their survival due to the lack of definitive treatment of the primary bladder tumour, by developing new invasive tumours in the bladder.

“Response to chemotherapy may be confounded by patient selection. However, it is a prognostic factor for treatment outcome and eventual survival…”

For bladder preservation strategies, response is evaluated by cystoscopy/re-TURB plus eventual CT-imaging, followed by close surveillance. This approach is prone to an immanent staging error and might put the patient at risk for local recurrence and/ or consecutive metastatic disease.

Response to chemotherapy may be confounded by patient selection. However, it is a prognostic factor for treatment outcome and eventual survival. Patientrelated factors combined with molecular markers (p53, p21, mdm-2, bcl-2) and gene profiling might

help to identify those who will respond well to chemotherapy and to further select patients for bladder preservation strategies. Prospective translational research programs should be incorporated in clinical trials to validate their role.

In the palliative setting, unresectable tumours or bladder primary tumours in advanced or metastasised patients, chemotherapy can promote local control in a substantial number of patients and a survival benefit.

For very selected patients with localised disease, a bladder conserving strategy with TURB and systemic cisplatin-based chemotherapy, preferably with MVAC, has been shown to allow long term survival with intact bladder6. Of note, this approach cannot be recommended for routine use.