Restaging procedures, criteria of response, and relationship between pathological response and survival

The first priorities for upfront chemotherapy in TCCB are to prove in randomized phase III trials that the addition of toxic chemotherapy to toxic standard locoregional treatment can improve survival and/or permit bladder preservation. If such proof is obtained, we will need to distinguish patients who benefit from chemotherapy from those who do not. One way to make such a distinction is to separate responders from nonresponders. The prognostic value of downstaging to P0 or noninvasive cancer is significantly different from the prognosis associated with the continued presence of invasive disease. The available data regarding clinical assessment of response still appear to indicate that only the demonstration of a lack of response (see Table 2: cIR, cSD, cPD, greater than or equal to cT2) is reliable, However, there may be some patients, who after two courses of chemotherapy, still show the presence of invasive bladder cancer together with signs of tumor cell kill and may be further downstaged to P0 during the next two courses of chemotherapy. The clinical assessment of cCR and cPR is too inaccurate to be used as a basis for decisions concerning continuation of chemotherapy or bladder preservation. The decision to leave the bladder untreated after a cCR carries the risk of jeopardizing cure. More studies on the evaluation of response of the primary tumor are needed, probably with a central role for the pathologist to evaluate not only the gross presence, minimal residual disease, or true absence of cancer but also the adequacy of site and deepness of the restaging TUR biopsy.