Brachytherapy combination improves PSA-free Survival for patients with higher-risk localized prostate cancer, trial finds

Brachytherapuy seeds placement
Brachytherapy – where seeds are placed.

April 29, 2015. Many patients with higher-risk localized prostate cancer are treated with external beam radiation or with brachytherapy (seed implants). A clinical trial conducted by Dr James Miller (right) of Vancouver, Canada has found that patients receiving permanent implant brachytherapy “seeds” plus a boost of radiation have a better chance of long-term survival than those treated with higher dose-escalated external beam radiotherapy but without the implants.

Men receiving the radioactive “seeds” were more likely to be cancer-free five to nine years later.

The aim of the trial was to measure biochemical progression–free survival (b-PFS), defined as an increase in PSA level of 2 ng/mL or more above the nadir (lowest level attained after treatment).

Dr. JAmes Morris
Professor James Morris MD, Radiation Oncologist
British Columbia Cancer Agency (BCCA)

James Morris MD of the Department of Radiation Oncology, Vancouver Cancer Centre, Canada said that the ASCENDE-RT1 trial is the first and only existing trial comparing low-dose-rate prostate brachytherapy (LDR-PB using iodine 125 seeds) for curative treatment of prostate cancer with any other method of radiation therapy delivery. Dr. Morris presented his team’s findings at a forum (ESTRO) in Barcelona, Spain on April 26.

The trial enrolled 398 men with cancer that had not spread outside the prostate gland. On the basis of standard tests, these patients were judged to be at high risk of the treatment failure called “biochemical recurrence,” symptomized by recurrence of rising PSA.

Entry requirements for the trial included:

  • Biopsy-proven prostate cancer stage T1c -T3a.
  • PSA below 40 ng ml-1.
  • Intermediate risk disease involving one or more of: bilateral palpable intra-capsular disease, Gleason score= 7, or PSA >10 and 20.
  • No evidence of nodal or distant metastasis in patients with Gleason sum 8 and/or PSA above 20
  • Patients with clinical or pathological evidence of seminal vesicle invasion (stage T3b) or involvement of adjacent pelvic organs/structures (stage T4) were excluded.

All the patients consented to 12 months of androgen deprivation treatment by means of injections of a standard castration drug aimed at reducing levels of the male hormones that stimulate prostate cancer cells to grow.

Eight months into chemical castration, all patients received 46 Gy (Gray – a measure of radiation dose) of external beam radiotherapy to the prostate and regional lymph nodes.

Following this, 198 men received low dose brachytherapy (LDR-PB) in which tiny radioactive seeds were implanted in the prostate gland while patients were under general or spinal anesthesia.

The other 200 patients were randomized to dose-escalated external beam radiation therapy and received an additional 32 Gy of external beam radiation to achieve a total prostate dose of 78 Gy.

“At five years follow up, we saw a large advantage in progression-free survival in the LDR-PB group,” Morris says. “Although, to date, overall survival and prostate cancer-specific survival do not appear to differ between the two groups, existing trends favor LDR-PB and an overall survival advantage is likely to emerge with longer follow-up.”

LDR-PB is a cost-effective treatment, the researchers say, but it does require prolonged training and experience in order to produce consistent results, and this may limit more widespread adoption. An additional problem is that, in the trial, the LDR-PB patients experienced more urinary side effects than those who received DE-EBRT.

Increased urinary side effects for the brachytherapy patients

In a separate presentation Prof Morris’s Clinical Research Fellow, Dr Sree Rodda, told the conference that the incidence of severe late urinary side effects was three times higher in patients who received LDR-PB than in those who had DE-EBRT.

“Many of these severe adverse effects were temporary and reversible, or could be ameliorated by procedures. Moreover, more than 80% of patients in the LDR-PB arm had few or no long term urinary side effects,” Rodda said.

Nonetheless, “the long-term prevalence of severe urinary toxicity in the LDR-PB patients was 8% compared to just 2% for the DE-EBRT patients. An important challenge for the future will be the reduction of these adverse effects while maintaining the advantages of LDR-PB.”

At British Columbia Canada’s five cancer centers, this treatment plan, known as LDR-PB boost, is now regarded as the standard of care for unfavorable risk localized prostate cancer.

So far, Professor Morris points out, randomized controlled trials to compare LDR-PB boost against its principal alternatives — temporary high-dose-rate brachytherapy implants (HDR-PB)3, stereotactic body radiation therapy using extreme hypofractionation, and combined surgery and post-operative radiation therapy — have not been undertaken. Such trials, Morris says, are “the ideal next step.”

Philip Poortmans, President of ESTRO, commented: “This study illustrates very nicely how the best results can be obtained by combining various treatment options instead of trying to get the most out of one single modality. Brachytherapy is an extremely efficient and safe radiation oncology modality, and this trial shows that it can have a wider field of applicability than simply in very localised and low risk tumors when combined with other techniques — in this case, androgen deprivation therapy and external beam radiation therapy.”

Sources and Links and Disclosures

Professor James Morris MD

Morris: abstract no. OC-0485: “LDR Brachytherapy is Superior to 78 Gy of EBRT for Unfavourable Risk Prostate Cancer: The Results of a Randomized Trial.”

Rodda: abstract no. PD-0047 GU and GI toxicity in ASCENDE-RT*: A Multicentre Randomized Trial of Dose-Escalated Radiation for Prostate Cancer, poster session

Protocol for the trial (which is continuing as the original patients are followed up):

Androgen Suppression Combined With Elective Nodal and Dose Escalated Radiation Therapy

The research was funded entirely by unrestricted educational grants to the BCCA from:

– Oncura Corporation (a subsidiary of GE Healthcare and the manufacturer of the radioactive seeds used in the trial).

– Sanofi-Aventis, Canada (the maker of the Suprefact and Eligard anti-androgen injections used in the trial).

This article was compiled and edited by J. Strax based on a press release by European Society for Radiotherapy and Oncology (ESTRO) and information gathered from clinicaltrials.gov and NCBI’s pubmed.gov Last modified 3.21 pm EST

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