What is the optimal regimen for BCG intravesical therapy? Are six weekly instillations necessary?

Objective: For more than 20 years, BCG intravesical therapy schedule has in cluded 6 weekly instillations. Very few studies have, however, analyzed the rationale of this regimen. We previously demonstrated that intravesical BC G induced an increased peripheral immune response against mycobacterial ant igens as compared to pretreatment values. In the present work, we have stud ied the weekly evolution of this immune response induced by intravesical BC G instillations. Materials and Methods: The evolution of the lymphoproliferative response of peripheral blood mononuclear cells against BCG culture filtrate (CF), tube rculin (PPD) a nd BCG extract (EXT) was tested before, every week during th e BCG instillations and at 3 and 6 months follow-up in 9 patients with supe rficial bladder cancer treated with 6 weekly BCG instillations. Lymphoproli feration was measured by means of a tritiated thymidine incorporation test. Results: A significant increase in the lymphoproliferative response against PPD, CF and EXT was observed in 9, 8 and 7 of the 9 patients, respectively , as compared to pre-BCG values. The maximal lymphoproliferation was achiev ed after 4 instillations in 4/5 patients initially reactive against mycobac terial antigens whereas 2 of 4 initially nonreactive patients required 6 in stillations. At 6 months' follow-up, lymphoproliferation against BCG and th e other mycobacterial antigens returned to pre-BCG values in all patients. In 3 patients who received additional instillations because of tumor recurr ence within 1 year of follow-up, the maximum immune response was observed a lready after 2 instillations. Conclusion: in most patients, the maximal peripheral immune response is alr eady observed after 4 weekly instillations. However, patients not previousl y immunized against mycobacterial antigens may require 6 weekly instillatio ns to achieve a maximum stimulation level. Our data support the need to fur ther evaluate the role of this status before starting BCG instillations. It could be of interest to study whether 6 BCG instillations are really neces sary in patients previously immune against mycobacterial antigens. Copyrigh t (C) 2000 S. Karger AG, Basel.