University of British Columbia Archives

Bladder Sparing Regimens for Muscle Invasive Disease: Should We Be Doing this More?

Posted by Peter Black, MD, FACS, FRCSC | Mar 2023

Peter Black, MD, FACS, FRCSC, discusses trimodal therapy (TMT) as a bladder-sparing option for some patients with muscle-invasive bladder cancer (MIBC).

Brachytherapy: The Royal Flush of Radiation Treatment for Men with High-Risk Prostate Cancer

Posted by Mira Keyes, MD, FRCPC, FABS | Oct 2022

Mira Keyes, MD, FRCPC, a Clinical Professor at the University of British Columbia (UBC) and a radiation oncologist at the Vancouver Centre of the British Columbia Cancer Agency (BCCA), discusses the benefits of prostate brachytherapy (PB) for men with high- and very high-risk prostate cancer. Dr. Keyes explains PB has excellent long-term outcomes (with the best cure rates of all radiation therapy [RT] treatments), requires less androgen deprivation therapy (ADT), has less downstream toxicity and lower cost than alternatives, calling it a “royal flush” treatment when used as a boost with external beam radiation therapy (EPRT).

ADT and Brachytherapy: The Good, the Bad, and the Ugly

Posted by Mira Keyes, MD, FRCPC, FABS | Jun 2022

As part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society and Grand Rounds in Urology, Mira Keyes, MD, FRCPC, FABS, Clinical Professor at the University of British Columbia (UBC) and a radiation oncologist at the Vancouver Centre of the British Columbia Cancer Agency (BCCA), discusses the pros and cons of using androgen-deprivation therapy (ADT) with brachytherapy to treat prostate cancer. After briefly discussing how ADT affects the tumor microenvironment, Dr. Keyes goes over the numerous clinical trials that have investigated how to combine external beam radiation together with hormone therapy. She explains that these trials found that the combination increases overall survival ~10-13% over ADT or EBRT alone, and longer ADT has a greater impact on OS, even with high radiation therapy dose. Dr. Keyes observes that ASCO considers brachytherapy a standard of care and recommends it be combined with ADT for unfavorable intermediate-risk and high-risk disease. She then considers the findings of ASCENDE-RT, the HDR UK trial, and the TROG 0.304 RADAR trial, all of which looked at the combination of ADT and brachytherapy, and discusses several ongoing randomized controlled trials on the role of ADT with prostate brachytherapy. Dr. Keyes also discusses a systematic literature review of ADT + prostate brachytherapy which concludes that the addition of ADT to brachytherapy provides no benefit to cancer-specific survival with ADT, and no benefit to overall survival with ADT, but does provide up to a 15% benefit to biochemical progression-free survival. She also notes that some believe dose escalation (prostate brachytherapy boost) may obviate the need for ADT in some high-risk patients. Dr. Keyes looks at a different meta-analysis which found that the addition of ADT to external beam radiation therapy provided a greater oncologic benefit than a brachytherapy boost and that there was a high probability that intermediate-risk and high-risk prostate cancer treated with EBRT + ADT would have superior overall survival to high-risk patients treated with EBRT + brachytherapy boost. Dr. Keyes argues that this paper misses the fact that the benefit of brachytherapy is that if brachytherapy is used, the duration of ADT can be reduced in unfavorable intermediate-risk and high-risk patients, which has a significant positive impact on quality of life and overall survival. She notes that ADT has numerous negative effects on quality of life, including erectile dysfunction, dementia, osteoporosis, metabolic syndrome, and more. Dr. Keyes particularly focuses on the negative cardiovascular effects from ADT, noting that observational data shows excess cardiovascular morbidity and mortality in patients on ADT with pre-existing cardiovascular disease. She concludes that ADT should be avoided in low- and intermediate-risk prostate cancer patients treated with monotherapy, that ADT for only 12 months in unfavorable intermediate- and high-risk patients is supported by randomized controlled trials, that ADT can be omitted in selected unfavorable intermediate- and high-risk patients, and that shorter ADT duration will improve quality of life and may increase overall survival by decreasing cardiovascular disease morbidity.

A Biochemical Definition of Cure Following Brachytherapy of Prostate Cancer

Posted by Juanita M. Crook, MD, FRCPC | Apr 2022

As part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society (ABS) and Grand Rounds in Urology, Juanita M. Crook, MD, FRCPC, Professor of Radiation Oncology at the University of British Columbia in Kelowna, discusses the development of a biochemical definition of cure following low-dose-rate (LDR) prostate brachytherapy. She begins with some background, explaining that the interpretation of post-radiation PSA values has been challenging. She relates that the 1996 ASTRO consensus conference defined biochemical failure as 3 consecutive rises after the nadir with failure backdated to midway between the nadir and the first rise, while the 2005 Phoenix consensus conference defined biochemical failure as 2 ng/ml > nadir, a definition still widely used today. Dr. Crook emphasizes that neither definition was meant to be a trigger for intervention, and neither attempted to define cure. She then discusses research on the importance of PSA nadir in LDR brachytherapy which showed that if PSA at 4 years was less than 0.2 to 0.4 ng/ml, patients tended to do well, but if it was greater than 1.0, the majority were going to fail. Dr. Crook considers another study on long-term PSA stability after LDR brachytherapy which found that 86% of patients had stable PSA at a median followup of 89 months. She also briefly notes that a study of intermediate-risk patients undergoing external beam radiation therapy (EBRT) + high-dose-rate brachytherapy boost found similar results to the studies of LDR brachytherapy regarding the importance of PSA nadir. Dr. Crook then goes into detail about a study she and her colleagues conducted to define a biochemical definition of cure following LDR brachytherapy by identifying a PSA threshold value at an intermediate follow-up time that is associated with long-term (10-15 year) freedom from prostate cancer. She explains that by using prospectively-collected data sets combined from 7 institutions, she and her colleagues were able to determine that patients with a PSA ≤ 0.2 ng/ml by 4-5 years have a 99% probability of being free of clinical failure at 10-15 years. Dr. Crook concludes that PSA ≤ 0.2 ng/ml should be adopted as biochemical definition of cure for comparison with surgical series, but highlights that those patients not achieving this threshold PSA should not be considered as having “failed” but should continue to be monitored with the understanding that they are at higher risk of subsequent clinical failure.

Brachytherapy for Prostate Cancer

Posted by Mira Keyes, MD, FRCPC, FABS | Feb 2022

As part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society and Grand Rounds in Urology, Mira Keyes, MD, FRCPC, FABS, Clinical Professor at the University of British Columbia (UBC) and a radiation oncologist at the Vancouver Centre of the British Columbia Cancer Agency (BCCA), gives an overview of brachytherapy for prostate cancer (PCa), making a case against its declining use based on its efficacy. She begins by introducing the American Brachytherapy society, which was founded in 1978 to provide insight, rationale, and research into the use of brachytherapy in the treatment of both malignant and benign conditions. Dr. Keyes then describes how brachytherapy was performed with radium tubes when it was invented in 1901, and was then subsequently done with needles beginning in 1915. She concludes her short history by marking 1983 as the beginning of the modern era of prostate brachytherapy, thanks to advances in imaging capabilities. Dr. Keyes discusses data showing that brachytherapy is associated with better survival in patients with local to advanced cervical cancer. She then goes over the processes for high dose rate and low dose rate brachytherapy for PCa, focusing on the quick recovery, high cure rates, and minimal to no incontinence or sexual dysfunction as benefits for both treatments. Dr. Keyes shows data on brachytherapy utilization for PCa depicting its decline since 2003 due to robotic prostatectomy use, PSA screening changes, active surveillance low-risk treatment recommendation changes, and higher reimbursement for IMRT and robotic surgery. She also discusses data showing that 10% of US cancer care spending is on prostate cancer, with the highest procedure cost per patient going to robotic surgery. Dr. Keyes compares the use of brachytherapy in the US to that of Canada, stating that Canada’s increasing use is due to a reimbursement system that incentivizes brachytherapy, and the education of the public, residents, general practitioners, and urologists. She concludes that the benefits of brachytherapy support its use for localized PCa in the US.