Intravesical Therapy
Post op chemo decreases recurrence by 11%. (9) Low risk patients should not get BCG or induction intravesical chemo. (10)
EPIRUBICIN and MITOMYCIN C
A single dose of intravesical epirubicin or mitomycin for 1-2 hrs within 24 hours of TURBT reduces recurrence but no progression or overall mortality. Three separate meta-analyses have reported that a single postoperative instillation of chemotherapy significantly decreases tumor recurrence between 10-15% compared to TURBT alone. The number needed to treat is about 8.5. (1,2,3)
GEMCITABINE
Intravesical gemcitabine has a side effect profile similar to placebo and a recent multicenter RCT showed a 12% reduction in recurrence of low grade NMIBC. (4) Another RCT showed 25% reduction in recurrence. (8) In fact, a meta-analysis comparing to BCG found that intravesical gemcitabine had lower dysuria and hematuria and no statistical differences in risk of recurrence, progression, incidence of fever, and any adverse events compared to BCG. (7) Intravesical gemcitabine was associated with a trend toward better DFS with significantly lower toxicity when compared with BCG. (13)
SALINE
Post TURBT normal saline irrigation has shown some possible benefit with a 6% non-statistically significant reduction in recurrence in a RCT (5) and shown benefit in nonrandomized studies. (6)
BCG
Low risk BCa patients do not get BCG. (9) High risk bladder cancer have 80% recurrence rate and 50% progression rate. A 3 year induction/maintenance protocol shown in SWOG 8507 and EORTC 30911 decreases metastasis and mortality. SWOG 8507 showed early BCG failure (3mo) could be salvaged in 64% of patients with a 2nd induction BCG. A meta-analysis compared to intravesical gemcitabine showed no difference in progression and recurrence and decreased hematuria and dysuria with the gemcitabine regimen. (7) While BCG does reduce progression and recurrence, a meta analysis found progression is reduced only if maintenance therapy is used. (11) A large 2013 study found there was no difference between 1/3 dose and full dose and no difference between 1 year and 3 years therapy. (14)
BCG SEPSIS
One case report of BCG sepsis 5years after BCG occurred in a renal transplant patient. (12)
DOCETAXEL
Intravesical docetaxel has been used. A 2020 retrospective analysis of patients with recurrence after BCG found encouraging results with using docetaxel and gemcitabine. (15)
MULTIAGENT
A 2020 report of a phase 1 trial had encouraging results for cabaziataxel, gemcitabine, cisplatin for BCG unresponsive or recurrent/relapsing UCC in bladder. (16)
A single dose of intravesical epirubicin or mitomycin for 1-2 hrs within 24 hours of TURBT reduces recurrence but no progression or overall mortality. Three separate meta-analyses have reported that a single postoperative instillation of chemotherapy significantly decreases tumor recurrence between 10-15% compared to TURBT alone. The number needed to treat is about 8.5. (1,2,3)
GEMCITABINE
Intravesical gemcitabine has a side effect profile similar to placebo and a recent multicenter RCT showed a 12% reduction in recurrence of low grade NMIBC. (4) Another RCT showed 25% reduction in recurrence. (8) In fact, a meta-analysis comparing to BCG found that intravesical gemcitabine had lower dysuria and hematuria and no statistical differences in risk of recurrence, progression, incidence of fever, and any adverse events compared to BCG. (7) Intravesical gemcitabine was associated with a trend toward better DFS with significantly lower toxicity when compared with BCG. (13)
SALINE
Post TURBT normal saline irrigation has shown some possible benefit with a 6% non-statistically significant reduction in recurrence in a RCT (5) and shown benefit in nonrandomized studies. (6)
BCG
Low risk BCa patients do not get BCG. (9) High risk bladder cancer have 80% recurrence rate and 50% progression rate. A 3 year induction/maintenance protocol shown in SWOG 8507 and EORTC 30911 decreases metastasis and mortality. SWOG 8507 showed early BCG failure (3mo) could be salvaged in 64% of patients with a 2nd induction BCG. A meta-analysis compared to intravesical gemcitabine showed no difference in progression and recurrence and decreased hematuria and dysuria with the gemcitabine regimen. (7) While BCG does reduce progression and recurrence, a meta analysis found progression is reduced only if maintenance therapy is used. (11) A large 2013 study found there was no difference between 1/3 dose and full dose and no difference between 1 year and 3 years therapy. (14)
BCG SEPSIS
One case report of BCG sepsis 5years after BCG occurred in a renal transplant patient. (12)
DOCETAXEL
Intravesical docetaxel has been used. A 2020 retrospective analysis of patients with recurrence after BCG found encouraging results with using docetaxel and gemcitabine. (15)
MULTIAGENT
A 2020 report of a phase 1 trial had encouraging results for cabaziataxel, gemcitabine, cisplatin for BCG unresponsive or recurrent/relapsing UCC in bladder. (16)
- Abern MR, Owusu RA, Anderson MR et al: Perioperative intravesical chemotherapy in non-muscle- invasive bladder cancer: a systematic review and meta-analysis. J Natl Compr Canc Netw 2013;11:477.
- Sylvester RJ, Oosterlinck W and van der Meijden AP: A single immediate postoperative instillation of chemotherapy decreases the risk of recurre26nce in patients with stage Ta T1 bladder cancer: a metaanalysis of published results of randomized clinical trials. J Urol 2004;171:2186.
- Perlis N, Zlotta AR, Beyene J et al: Immediate post-transurethral resection of bladder tumor intravesical chemotherapy prevents non-muscle-invasive bladder cancer recurrences: an updated meta-analysis on 2548 patients and quality-of-evidence review. Eur Urol 2013;64:421.
- Messing, Edward M., et al. "Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non–Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial." Jama 319.18 (2018): 1880-1888.
- Whelan, P., et al. "Preliminary results of a MRC randomised controlled trial of post-operative irrigation of superficial bladder cancer." Brit J Cancer 85 (2001): 1-1.
- Sylvester, Richard J., et al. "Systematic review and individual patient data meta-analysis of randomized trials comparing a single immediate instillation of chemotherapy after transurethral resection with transurethral resection alone in patients with stage pTa–pT1 urothelial carcinoma of the bladder: which patients benefit from the instillation?." European urology 69.2 (2016): 231-244.
- Ye, Ziqi, et al. "The efficacy and safety of intravesical gemcitabine vs Bacille calmette-guérin for adjuvant treatment of non-muscle invasive bladder cancer: a meta-analysis." OncoTargets and therapy 11 (2018): 4641.
- Bosschieter, Judith, et al. "An immediate, single intravesical instillation of mitomycin C is of benefit in patients with non–muscle-invasive bladder cancer irrespective of prognostic risk groups." Urologic Oncology: Seminars and Original Investigations. Elsevier, 2018.
- NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer. Accessed 10/26/18
- AUA Guidelines: NMIBC. Accessed 10/26/18
- Sylvester, Richard J., ADRIAN PM van der MEIJDEN, and Donald L. Lamm. "Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials." The Journal of urology 168.5 (2002): 1964-1970.
- Ziegler, Jennifer, et al. “Disseminated Mycobacterium Bovis Infection Post‐kidney Transplant Following Remote Intravesical BCG Therapy for Bladder Cancer.” Transplant Infectious Disease, vol. 20, no. 5, 2018.
- Prasanna, Thiru, et al. “Intravesical Gemcitabine versus Intravesical Bacillus Calmette–Guérin for the Treatment of Non-Muscle Invasive Bladder Cancer: An Evaluation of Efficacy and Toxicity.” Frontiers in Oncology, vol. 7, 2017.
- Oddens, Jorg, et al. "Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guerin in intermediate-and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance." European urology 63.3 (2013): 462-472.
- Steinberg, Ryan L., et al. "Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy for Nonmuscle Invasive Bladder Cancer." The Journal of Urology 203.5 (2020): 902-909.
- DeCastro*, G. Joel, et al. "MP43-14 A PHASE 1 TRIAL OF INTRAVESICAL CABAZITAXEL, GEMCITABINE, AND CISPLATIN (CGC) FOR THE TREATMENT OF NON-MUSCLE INVASIVE BCG UNRESPONSIVE UROTHELIAL CARCINOMA OF THE BLADDER." The Journal of Urology 201.Supplement 4 (2019): e623-e623.