BCG Therapy Significantly Reduced Recurrence and Progression in High Risk Non-Muscle-Invasive Bladder Cancer

Introduction

The rate of recurrence of non-muscle-invasive bladder cancer (NMIBC) has been reduced with intravesical Bacillus Calmette Guerin (BCG) therapy. However, ambiguity on whether BCG therapy prevents or delays progression to metastases or decreases cancer-specific mortality (CSM) still exists. There are conflicting reports on the effect of BCG therapy on the progression or CSM in patients at high risk of NMIBC.

Aim

To evaluate the long-term effect of BCG on recurrence, progression and CSM in patients at a high risk of developing NMIBC.

Patient Profile

• Cases with high risk NMIBC
• High risk NMIBC was defined as all non-muscle-invasive T1 and all G3 tumors eg T1G1-G3, TaG3 and primary and secondary carcinoma in situ (CIS)
• All the patients underwent transurethral resection (TUR-BT)
• Treatment options were TUR-BT only or with adjuvant intravesical chemo or immunotherapy
• Second resection was recommended only when tumor size was >3 cm

Method

Study Design

Prospective study

Treatment Strategy

• Out of 140 cases, 82 (59%) received BCG as induction course of 6 weekly instillations
• Maintenance treatment either monthly or 3 weekly instillations every 3 months was recommended but not given as a single standard
• cystoscopy and cytology performed every 3 months during the 1^st year and every 6 months for 2^nd year and thereafter annually for 3 years

Endpoints

• recurrence defined as diagnosis of any new tumor in the bladder after initial staging and grading by TUR-BT
• progression defined as growth of initial tumor into muscular layer of the bladder or beyond, local and distant metastasis or death from bladder cancer
• Cancer-specific death defined as death from bladder cancer

Results

• Out of 140 patients, 1 was excluded due to inconsistent information on survival
• 78% were staged as T1, 14% as Ta and 8% as primary CIS
• 63% had G3 tumors
• 64% had tumors of size>3 cm
• Median follow up was 100 months
• The rate of recurrence after 15 years clinical follow up in BCG group and non-BCG group is shown in figure 1.

• The % patients with progression to T2NM in BCG group and non-BCG group is shown in figure 2.

• CSM rates in BCG group and non-BCG group is shown in figure 3.

• Overall death rates in BCG group and non-BCG group is shown in figure 4.

• BCG treatment significantly reduced the rates for recurrence (HR 0.40; p<0.0001) and progression (HR 0.52; p=0.038) but not for CSM

Conclusion

• Bacillus Calmette Guerin (BCG) therapy reduced the rate of recurrence in patients at high risk non-muscle invasive bladder cancer (NMIBC), irrespective of grade and stage of tumors
• BCG therapy significantly reduced progression in papillary tumors without concomitant carcinoma in situ
• The long term effect of BCG treatment makes it suitable as the first line adjuvant treatment in patients with high risk NMIBC
• The effect of BCG treatment on cancer-specific mortality is yet to be clarified

World J Urol. 2018 Jun 15. Doi: 10.1007/s00345-018-2375-7.