Dismissal of ASCENDE-RT LDR boost findings restricts life-enhancing treatment opportunities for inte

Recent questioning - even dismissal - of the ground-breaking ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) trial data highlight a blinkered view of prostate cancer treatment options. Yet both trial and on-the-ground evidence provide an opportunity to challenge clinical practice, expand treatment options and improve health outcomes for intermediate- and high-risk prostate cancer patients and cannot be ignored.

The first randomized, controlled trial to compare the use of a dose-escalated external beam radiation therapy (DE-EBRT) versus low-dose-rate prostate brachytherapy (LDR-PB) boost in combination with external beam radiotherapy in men with intermediate and high-risk prostate cancer, ASCENDE-RT provides level-one evidence that LDR-PB offers significantly improved biochemical progression free survival.

Despite this, sceptics are choosing to highlight the study’s toxicity level data. Specifically that “Cumulative 5-year grade 3 urologic toxicity was found to be significantly higher in the LDR-B group compared to the DE-EBRT group (19% vs 5%, p < 0.001). The prevalence of late grade 3 or higher toxicity was noted to be higher in the LDR-B group (8%) compared to the DE-EBRT group (~2%).” Yet <80% of patients in the LDR group reported no or minimal GU side effects.

Equally, others dismiss the data saying surgery gives an equivalent result, but with no evidence to support the claim!

However, according to brachytherapy specialist consultants, both assertions are fundamentally flawed. Dr. James Morris asserts that increased GU toxicity is likely related to irregular dose planning and obsolete imaging technology, which have changed substantially. Toxicity levels, if monitored using todays’ procedures, would be much lower. Moreover, morbidity levels today are being managed more effectively than they were at the start of the ASCENDE-RT study 10 years ago, through a new clinical protocol being used by treatment centres where the LDR-B boost has changed from 115Gy to 110Gy and the prostate and seminal vesicles are treated instead of the whole pelvis.

Likewise, he argues, comparative results for surgery simply don’t compare: After LDR-PB boost, the 10 year biochemical progress free survival is around 80% using the surgical threshold of >0.2 ng/mL. Yet the 5 year rate* after surgery for Gleason 4+3 =7 is 65.1%.

A recent multi-institutional comparative analysis**, as published in the European Urology Journal (May 2017), supports the ASCENDE-RT findings. This significant study sought to establish optimal treatment for patients and considered over 25,000 people globally. Within this, the outcomes of 487 patients with Gleason 9-10 treated between 2000 – 2013 with EBRT, EBRT & brachytherapy (BT), and Radical Prostatectomy (RP) were compared. As with ASCENDE-RT, this study found that five-year and 10-year distant metastasis-free survival rates were significantly higher with EBRT + BT (94.6% and 89.8%) than with EBRT (78.7% and 66.7%, p = 0.0005) or RP (79.1% and 61.5%, p < 0.0001). Indicating that even for the highest risk patients, brachytherapy boost is the most effective treatment option.

Dr. Morris says: “ASCENDE-RT provides irrefutable, level-one evidence that an LDR-PB boost in combination with external beam radiation therapy is superior to a DE-EBRT. Patients receiving a DE-EBRT boost are twice as likely to experience biochemical failure compared to LDR-PB boost. ASCENDE-RT shows that at 9 years biochemical progression free survival in the LDR-PB arm was 83% compared to 62% in DE-EBRT boost subjects.”

The study also highlights a significant difference in PSA values in subjects treated with an LDR-PB boost. Nadir PSA is an important post-treatment metric, with low PSA values considered the best indicator of long-term biochemical progression-free survival. In non-relapsed LDR-PB subjects with at least 4 years’ follow-up, 54% of patients had undetectable PSA levels, compared to just 8% in DE-EBRT subjects. Median PSA levels were 0.01 ng/mL and 0.25 ng/mL respectively.

The findings of the ASCENDE-RT trial are reinforced by those from brachytherapy treatment centres such as Belfast Hospital in Northern Ireland. Dr. Darren Mitchell, Consultant Clinical Oncologist at the Belfast Health and Social Care Trust first carried out the combination therapy in Northern Ireland in 2009.

He says: “Treatment options have significantly evolved in recent years, in particular brachyt