Do prognostic parameters of remission versus relapse after Bacillus Calmette-Guérin (BCG) immunotherapy exist?. analysis of a quarter century of literature.

OBJECTIVE: To review prognostic factors identified in clinical trials for remission versus relapse after intravesical adjuvant Bacillus Calmette-Guérin (BCG) immunotherapy for superficial bladder cancer (Ta, T1, and carcinoma in situ).

MATERIALS AND METHODS: Information was retrieved by a MEDLINE search of the English literature. Indexing terms comprised bladder cancer, bladder neoplasm, BCG vaccine, superficial bladder cancer, immunotherapy, intravesical therapy, prognostic marker, and Bacillus Calmette-Guérin. Fifty clinical studies were assessed for the strength of their results on the therapeutic response to BCG instillation. Emphasis was placed on clinical trials that assessed tumor and/or host characteristics, immunological reactions, recurrence rates, progression rates and disease-specific survival after BCG.

RESULTS: The predictive value of host factors is extremely controversial, but marked adverse reactions to BCG instillation appear to be associated with a better tumor response. Traditional pathological tumor characteristics, molecular markers (p53) and immunological status (PPD skin test) do not appear to have prognostic value in this setting. There is increasing evidence that immunologic markers are predictive of the BCG response, but most of them have not yet been assessed in large prospective studies. Histologic/cytologic response criteria are the critical determinant of post-BCG outcome.

CONCLUSIONS: After a quarter century of clinical research, no independent prognostic factor for the bladder tumor response to BCG has yet been identified. Sophisticated individual therapeutic approaches (SITA) appear to be the most promising. Nomograms based on host, tumor and immunological characteristics may help with clinical decision-making and with rationalized BCG schedule design.