Treatment efficacy and tolerability of intravesical Bacillus Calmette-Guerin (BCG) - RIVM strain: induction and maintenance protocol in high grade and recurrent low grade non-muscle invasive bladder cancer (NMIBC)

Abstract

BackgroundBCG-RIVM strain was used in many treatment protocols for non-muscle invasive bladder cancer only as induction courses. Cho et al. (Anticancer Res 2012) compared BCG-RIVM induction and 'standard' maintenance (Lamm et al., J Urol. 2000) to mitomycin C. They found no statistically significant differences regarding disease recurrence and progression. The purpose of our study was to determine the efficacy & tolerability of this specific BCG RIVM strain, using six-weekly, induction course and single monthly instillations as maintenance for one year, in high risk recurrent, multifocal low grade and multifocal high grade pTa/pT1, CIS transitional cell carcinoma of bladder.MethodsFrom 2003 - 2012, BCG-naive patients treated with intravesical BCG-RIVM for high-risk multifocal NMIBC were identified. Transurethral resection of bladder tumor (TURBT) and re-staging TURBT within six weeks, was done for accurate staging and complete elimination of disease. A six-weekly induction course, started 2-3 weeks after the last TURBT, followed by monthly maintenance protocol for one year. Recurrence, progression, cystectomy free survivals, cancer specific and over-all survival were determined.ResultsSixty evaluable patients - median age 63, median follow-up 3.98 years. Forty-two patients (70%) completed BCG-RIVM treatment as planned. BCG termination was necessary in 18 patients (30%). Recurrence occurred in 16 patients (26.7%) at a median follow-up of 24.2 months while progression occurred in five patients (8.3%) at a median follow-up of 33 months. Recurrence-free survival and progression-free survival rates were 73% and 92% respectively. Cystectomy was performed in seven patients (12%) with a cystectomy-free survival of 88%. There were no cancer specific deaths. Two patients died of other causes (3.3%). The overall survival rate was 97%.ConclusionsOur study is the first to show the clinical efficacy and tolerability of BCG-RIVM strain in the management of high risk NMIBC when given in a schedule of six-weekly induction with monthly maintenance for one year. Our maintenance protocol, achieved equivalent recurrence-free, progression-free, disease specific survival and overall survival to the reported literature and the more intense three-years South West Oncology Group (SWOG) protocol.

The Moreau Strain of Bacillus Calmette-Guerin (BCG) for High-Risk Non-Muscle Invasive Bladder Cancer: An Alternative during Worldwide BCG Shortage?

“…In our cohort, the 5-year RFS rate was 65%, which is in concordance with current literature with rates ranging between 59 and 69% with the other strains [16,21,25]. Similar, the 5-year PFS rate of 81% is in line with recent studies reporting rates between 72 and 84% with other strains [25,26,27,28,29].…”

“…Initially introduced in 1986, studies including this strain were basically limited to induction courses only. Recently, it has been shown that the RIVM strain for induction and maintenance leads to similar outcomes with regard to recurrence and PFS than other strains [21]. Unfortunately, the production has been on hold since the last quarter of 2014.…”

A retrospective analysis of patients treated with intravesical BCG for high-risk nonmuscle invasive bladder cancer

“…However, with subsequent instillations (as for the maintenance therapy) the immune stimulation peaks at 3 weeks and is suppressed at weeks 4 and 5. 25 In fact, we observed a recurrence rate of 22.2% and 2.94% in patients treated with monthly and SWOG maintenance protocols ( p = 0.217). Additionally, patients treated with the SWOG protocol had a progression rate of 2.94% and the monthly protocol had 11.1% ( p = 0.775).…”

Иммунотерапия Рака Мочевого Пузыря. Вакцина БЦЖ: Принципы Действия, Эффективность И Безопасность

“…Õîòÿ A. Sengiku et al [88] íå îáíàðóaeèëè ðàçíèöû â ýôôåêòèâíîñòè è áåçîïàñíîñòè âàêöèíû ÁÖAE Connaught è ÁÖAE Tokyo íà áëèçêèõ ïî êëèíè÷åñêîé õàðàêòåðèñòèêå ãðóïïàõ áîëüíûõ ÐÌÏ. Çíà÷èòåëüíîå ïðåèìóùåñòâî âàêöèíû ÁÖAE-RIVM ïðîäåìîíñòðèðîâàíî â ÊÈ, ïðîâåäåííûõ N. B. Farah et al [29], îäíàêî âûâîäû àâòîðîâ áàçèðóþòñÿ íà ðåçóëüòàòàõ, ïîëó÷åííûõ íà ìàëîì êîëè÷åñòâå íàáëþäåíèé.  äåòàëüíîì îáçîðå C. Gan et al [31] ïðîàíàëèçèðîâàíû ðàçëè÷èÿ ðàçíûõ øòàììîâ è âûñêàçàíî ïîëîaeåíèå î òîì, ÷òî òîëüêî íîâûå çíàíèÿ îá èììóíîãåíåòèêå, ñòðóêòóðå, ôóíêöèÿõ ìèêîáàêòåðèè è ïðèíöèïàõ åå âçàèìîäåéñòâèÿ ñ ìàêðîîðãàíèçìîì ìîãóò îáúÿñíèòü çíà÷èìîñòü ýòèõ ðàçëè÷èé äëÿ êëèíè÷åñêîé ïðàêòèêè, à òàêaeå èäåíòèôèöèðîâàòü áèîëîãè÷åñêèå ìàðêåðû ðåàêòîãåííîñòè è ýôôåêòèâíîñòè âàêöèíû ÁÖAE, ïðèìåíÿåìîé ïðè ÐÌÏ.…”