Dr. Lerner debated against BCG therapy in this particular case. T1G3 with CIS has a worse prognosis than a T1G3 tumor without CIS.1 It is also important to consider that these patients can be upstaged at a re-TUR. If they are shown to be upstaged, their survival is even worse.1 According to Dr. Lerner the correct and optimal treatment, in this case, should be early radical cystectomy.
Another important point to consider is that patients with T1G3 tumors that undergo delayed radical cystectomy compared to early radical cystectomy have worse cancer-specific survival (Figure 1). According to Dr. Lerner, our ultimate goal should be to intervene with definitive radical cystectomy prior to pathologic development of muscle invasion.
Early radical cystectomy should be performed in disease presenting as T1 progressing from Ta or Tis cancer, lymphovascular invasion (LVI)2 (due to its high risk of clinical under staging) and in primary T1G3 with the following features:
- Large volume/multifocal disease
- Multifocal CIS
- Persistent T1G3 on re-resection
Other strong indicators for cystectomy include unfavorable variant histology (Micropapillary, small cell carcinoma, squamous cell carcinoma, adenocarcinoma, and nested variant).
In a large meta-analysis of 73 studies with over 15,000 patients,3 including 98% T1HG tumors the following factors were shown to be predictors of undergoing early radical cystectomy:
- Depth of invasion
- LVI
- CIS
- Tumors size > 3 cm
- Older age
- Large tumor size
- High-grade tumor
- Poorly accessible tumor location
- Diffuse disease
- CIS
- LVI
- Prostatic urethral involvement
- Patients who recur with G3/high grade
The EAU guidelines recommend early cystectomy in:
- Multiple recurrent high-grade tumors
- T1G3 with or without CIS
- High-grade tumor + CIS
- Recurrent tumor after BCG
- Multiple large and / or recurrent T1G3
- CIS at the urethra
- Variant histology
- LVI
Dr. Lerner concluded his talk providing some important take-home messages.
- The T1 sub staging is an important concept, as infiltration of the muscularis mucosa may be associated with a higher risk of progression.
- First radical cystectomy should be performed for large tumors, extensive CIS, LVI, and variant histology.
- If there is no high-risk features and no T1 disease on re-resection, the treatment should be with BCG induction + 3 years of maintenance.
- Lastly, a recurrent T1HG tumor after BCG should be treated with radical cystectomy
Presented by: Seth Lerner, MD, Professor of Urology, Beth and Dave Swalm Chair in Urologic Oncology, Baylor College of Medicine, Houston, Texas
Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New York, USA, Twitter: @GoldbergHanan at the 39th Congress of the Société Internationale d'Urologie, SIU 2019, #SIUWorld #SIU2019, October 17-20, 2019, Athens, Greece
References:
1. Gupta A, Lotan Y, Bastian PJ, et al. Outcomes of patients with clinical T1 grade 3 urothelial cell bladder carcinoma treated with radical cystectomy. Urology 2008; 71(2): 302-7.
2. Tilki D, Shariat SF, Lotan Y, et al. Lymphovascular invasion is independently associated with bladder cancer recurrence and survival in patients with final stage T1 disease and negative lymph nodes after radical cystectomy. BJU international 2013; 111(8): 1215-21.
3. Martin-Doyle W, Leow JJ, Orsola A, Chang SL, Bellmunt J. Improving selection criteria for early cystectomy in high-grade t1 bladder cancer: a meta-analysis of 15,215 patients. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2015; 33(6): 643-50.