The surface has denuded, with replacement by a brisk underlying inflammatory process
The stroma is cellular due to numerous fairly discrete epithlelioid granulomas with touton giant cells (arrow); lymphocytes and eosinophils are also numerous
A mere remnant of the surface urothelium is seen along the top left. Underlying it is an inflammatory process with epithelioid granulomas and lymphocytes
Giant cells, foamy macrophages and lymphocytes comprise the inflammatory reaction
The stroma contains reactive fibroblasts and plasma cells and lymphocytes.
Of the estimated 68,000 new cases of bladder cancer in the USA in 2008, the majority are in situ or non-muscle-invasive tumors, over half of which can be effectively treatable by bacillus Calmette-Guérin (BCG). Patients with carcinoma in situ (CIS) treated with intravesical BCG plus interferon have a 60% to 70% chance of a complete and durable response if they were never treated with BCG.
BCG is an immunotherapy in which the response is driven both in the bladder and in peripheral circulation, with the production of IL-2, IFN-γ, IL-12 and IL-18 among other cytokines. The net effect of chemokine signals is an escalating recruitment of monocytic and granulocytic leukocytes into the bladder with each successive weekly BCG instillation.
In general, maintenance BCG of at least 2 cycles beyond the 6-week induction course is required to demonstrate an improvement in recurrence-free survival over induction alone.
A large study compared weekly BCG induction for 6 weeks (+) or (-) 3 weekly instillations at the 3rd and 6th month, and then every 6 months for up to 3 years (Lamm). Estimated median recurrence-free survival showed 35.7 months in the induction-only arm and 76.8 months in the maintenance arm. Overall 5-year survival was 78% in the induction-only arm and 83% in the maintenance arm.
Overall, approximately 30% to 40% of patients do not respond to BCG therapy and are considered "refractile". There are no predictors of which patients are more likely to fail this treatment. What constitutes BCG therapy failure is a matter of debate. By strict definition, any tumor recurrence of tumor after BCG therapy can be termed a BCG failure but not all failures under this definition have a similar prognosis. One good definition is that disease is defined as BCG refractory if there is persistent disease despite 6 months of initial BCG therapy (that may include either maintenance or re-treatment at 3 months secondary to persistent or recurrent disease). This category includes any progression in stage or grade by 3 months after the first cycle of BCG (Martin).
Grossman HB, et al. Bacillus calmette-guérin failures and beyond: contemporary management of non-muscle-invasive bladder cancer. Rev Urol. 2008 Fall;10(4):281-9.
Lamm DL, Blumenstein BA, Crissman JD, et al. Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol. 2000;163(4):1124-1129.
Martin FM, Kama AM. Definition and management of patients with bladder cancer who fail BCG therapy. Expert Review of Anticancer Therapy 9.6 (June 2009): p815(6).