Phase III research represents potential shift in standard of care for bladder cancer

April 2, 2012, American Association for Cancer Research

Use of the Connaught strain of bacillus Calmette-Guérin, an adjuvant immunotherapy used in the treatment of non-muscle-invasive bladder cancer, significantly reduced cancer recurrence compared with the Tice strain of bacillus Calmette-Guérin, according to data presented at the AACR Annual Meeting 2012, held here March 31 - April 4.

Cyrill A. Rentsch, M.D., Ph.D., of the division of urology at the University of Basel in Switzerland, presented the phase III data, which represent the potential for a shift in the standard-of-care for non-muscle-invasive .

Bacillus Calmette-Guérin (BCG) was originally developed as a vaccine for tuberculosis but has also been the standard of care for the treatment of noninvasive bladder cancer for more than 30 years. Currently, at least eight strains of BCG are used in treating bladder cancer.

"This is the first study demonstrating that different BCG strains lead to different clinical outcomes in the treatment of bladder cancer," Rentsch said.

He and his colleagues prospectively compared the efficacy of the Connaught and Tice strains in preventing recurrences and progression of cancer. They recruited and randomly assigned 149 patients to six weekly injections of Tice or Connaught. All patients had undergone surgery to remove visible bladder tumors.

After a median follow-up of 25 months, the five-year recurrence-free survival rate for all patients was 61 percent. Patients who underwent treatment with Connaught had significantly fewer recurrences compared with patients treated with Tice. The five-year recurrence-free survival for patients treated with Connaught was 75 percent compared with 46 percent for patients treated with Tice.

"At five years, this results in a more than twofold improvement in the recurrence rate in favor of BCG Connaught," Rentsch said. "Based on its common use, we estimate that more than 20 percent of the worldwide population is at risk to receive treatment with BCG Tice, a treatment that, based on our findings, is less effective in reducing recurrences than BCG Connaught."

These results have the potential to substantially improve the course of disease in many patients with non-muscle-invasive bladder cancer, according to Rentsch.

"As an example of clinically successful immunotherapy, it is a must to further dissect and understand the specific mechanisms underlying BCG immunotherapy," Rentsch said. "The genetic differences identified between the two strains might represent a start for further studies."

Explore further: New made-in-Canada therapy for bladder cancer shows promising results

More information:

A randomized phase III study comparing the efficacy of Bacillus Calmette Guérin strain Tice versus Connaught for immunotherapy of non-muscle invasive bladder cancer

Introduction: For almost forty years now, adjuvant immunotherapy with intravesical Bacillus Calmette Guérin (BCG) is standard of care in the treatment of non-muscle invasive bladder cancer (NMIBC). The question whether the choice of the different available BCG strains used for treatment influences treatment outcome is still under debate. We report on a randomized phase III study comparing the two most commonly used strains in Europe and the USA.
Patients and Methods: This study was performed under approval of the Cantonal Ethical Committee of Bern, Switzerland, to evaluate recurrence free survival in patients treated with BCG as the primary end-point. Between 1998 and 2010 149 patients (n=149) were recruited. Patients underwent transurethral resection of all visible bladder tumors or random bladder biopsies in case of a solely positive bladder wash cytology. TaG3 and T1G3 tumors underwent a second resection to confirm non-muscle invasive disease. Two to 15 days after surgery, patients were either randomized to receive six weekly intravesical instillations with 2-8x108 CFU OncoTice ® (BCG Tice) or 6.6-19.2 x108 CFU ImmuCyst ® (BCG Connaught) dissolved in 50 ml of saline according to manufacturers recommendations. Patients were followed in 3-monthly intervals for 3yrs, then in 6-monthly intervals by cystoscopy and bladder wash cytology. Relapses were confirmed by histology after transurethral surgery. Cox regression analysis and Log rank tests served for statistical analysis.
Results: Gender, age, tumor stage and grade were well balanced between the two treatment arms (p=0.38). Median follow up was 25 months (range: 0.3-136). Side effects did not differ between the two treatment arms (p=0.42). Age and gender did not have an impact on treatment response (p=0.71). Five year recurrence-free survival for all patients was 61%. Patients treated with Connaught had significantly less recurrences than patients treated with OncoTice (p<0.002). Five year recurrence-free survival was 75% and 46% for Connaught and Tice treated patients, respectively. Median recurrence-free survival was 28 months (range: 0.6-136) for Connaught and 22 months (range: 0.3-122) for Tice treated patients. Progression-free and overall survivals were not significantly different between the two treatment arms.
Conclusions: The choice of the BCG strain impacts on treatment outcome and favors the use of BCG Connaught over Tice in the treatment of NMIBC.

Related Stories

New made-in-Canada therapy for bladder cancer shows promising results

May 24, 2011
Clinical trials for a new bladder cancer therapy show promising interim results. Lead researcher Alvaro Morales says that the breakthrough using the drug Urocidin follows thirty years of his research in this important area.

Sonic Hedgehog variations linked to recurrence, survival and response to therapy of bladder cancer

December 9, 2009
Genetic variations in the Sonic Hedgehog pathway increase the likelihood of recurrence, reduce survival time and limit response to therapy for people with non-muscle invasive bladder cancer, scientists from The University ...

Genetic variants predict recurrence of bladder cancer, patient survival

April 20, 2009
Scientists at The University of Texas M. D. Anderson Cancer Center have discovered genetic variations in the inflammation pathway that reduce the likelihood of recurrence and increase survival of patients with non-muscle ...

Chemotherapy plus radiation prevents bladder cancer recurrences

October 25, 2010
Adding chemotherapy to radiation therapy for muscle invasive bladder cancer allows 67 percent of people to be free of disease in their bladders two years after treatment. This compares to 54 percent of people who receive ...

Nearly all patients with high-grade bladder cancer do not receive guideline-recommended care

July 11, 2011
A study at UCLA's Jonsson Comprehensive Cancer Center found that nearly all patients with high-grade, non-invasive bladder cancer are not receiving the guideline-recommended care that would best protect them from recurrence, ...

New treatment to reduce the relapse rate in bladder cancer patients

January 31, 2011
( -- A major bladder cancer trial, funded by Cancer Research UK, has shown that adding two commonly used chemotherapy drugs to traditional radiotherapy can reduce the chance of a patient's tumour coming back by ...

Recommended for you

In zebrafish, a way to find new cancer therapies, targeting tumor modulators

September 21, 2018
The lab of Leonard Zon, MD, at Boston Children's Hospital has long been interested in making blood stem cells in quantity for therapeutic purposes. Looking for a way to test for their presence in zebrafish, their go-to research ...

What can salad dressing tell us about cancer? Think oil and vinegar

September 20, 2018
Researchers led by St. Jude Children's Research Hospital scientists have identified another way the process that causes oil to form droplets in water may contribute to solid tumors, such as prostate and breast cancer. The ...

Novel biomarker found in ovarian cancer patients can predict response to therapy

September 20, 2018
Despite months of aggressive treatment involving surgery and chemotherapy, about 85 percent of women with high-grade wide-spread ovarian cancer will have a recurrence of their disease. This leads to further treatment, but ...

Testing fluorescent tracers used to help surgeons determine edges of breast cancer tumors

September 20, 2018
A team of researchers with members from institutions in The Netherlands and China has conducted a test of fluorescent tracers meant to aid surgeons performing tumor removal in breast cancer patients. In their paper published ...

Cancer immunotherapy might benefit from previously overlooked immune players

September 20, 2018
Cancer immunotherapy—efforts to boost a patient's own immune system, allowing it to better fight cancer cells on its own—has shown great promise for some previously intractable cancers. Yet immunotherapy doesn't work ...

New way to target advanced breast cancers

September 20, 2018
A cytokine signature found in certain kinds of breast cancer cells can not only serve as a diagnostic tool for HER2-negative cancers but also offer an effective treatment target.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.