Growing clinical evidence-base highlights long-term side effects and risks associated with the most popular prostate cancer treatments

There is currently no consensus as to the optimal treatment for localised prostate cancer, and urologists and radiation oncologists continue to debate the relative merits of therapies. Most men and their partners ultimately choose a therapy based on how well informed they are about the various options, their respective side effect profiles and personal lifestyle choices, and recommendation from their consultant.

Yet, for many men, this is a confusing and worrying time.  Men diagnosed with localised prostate cancer have numerous management options, including active surveillance, expectant management, androgen-deprivation (hormone) therapy, and definitive therapy with the intent to eradicate or cure the cancer.

Among patients who are offered these curative-intent treatments, the vast majority are offered either radical prostatectomy (surgery to remove the prostate) or radiation therapy. Radiation therapy, however, includes a range of treatments and dosing including external-beam based therapies that target the entire prostate region, high-dose-rate (HDR) or low-dose- rate (LDR) brachytherapy, and combinations of beam and brachytherapy, with or without hormone therapy. Choosing amongst these can be a daunting task.

However, there is a growing clinical evidence-base which suggests certain standard-practice treatment options and doses may not be as effective, and / or have significant long-term clinical side effects that clinicians and patients alike should be aware of.

Biochemical Recurrence following Radical Prostatectomy and Radical Radiotherapy

A 2018 systematic review of existing literature by Thomas van den Broeck et al^[1], on biochemical recurrence (BCR) – defined as the return of measurable PSA – found that BCR has an impact on survival, but that this effect appears to be limited to a subgroup of patients with specific clinical risk factors. Short PSA-DT (the PSA doubling time) and a high final Gleason score after Radical Prostatectomy, and a short Interval to Biochemical Failure or Recurrence (IBF) after Radical Radiotherapy and a high biopsy Gleason score are the main factors that have a negative impact on survival.

Radical Prostatectomy and Radical Radiotherapy are also widely recognised for the major possible side effects of urinary incontinence and erectile dysfunction, compared to other curative treatment options, such as brachytherapy.

Urinary Adverse Events after High- versus Low-Dose-Rate Brachytherapy with or without Radical (External-beam) Radiotherapy

A 2016 study comparing the incidence of severe urinary adverse events (UAEs) after low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy, as well as after LDR plus external beam radiation therapy (EBRT) and HDR plus EBRT^[2], found no statistically significant toxicity differences were observed between LDR and HDR. However, combination radiation therapy (either HDR plus EBRT or LDR plus EBRT) increases the risk of severe UAEs compared with HDR alone or LDR alone.

Single-dose High-Dose-Rate Brachytherapy

Most recently, a 2021 study by Shreya Armstrong et al of the Mount Vernon Cancer Centre, Northwood, UK^[3], undertook a retrospective review of treatment records of patients who received single-dose (fraction) HDR-B, concluding that long-term follow up of single dose HDR-B for localised prostate cancer has revealed higher than expected rates of biochemical and local failure and should therefore not be used as a monotherapy for intermediate- and high-risk cancer patients.

This is further backed up by a 2019 study from Leeds Teaching Hospitals NHS Trust comparing men with intermediate and high risk prostate cancer treated using LDR–EBRT and HDR–EBRT, which concluded that patients treated with HDR–EBRT were more than twice as likely to experience biochemical progression compared with LDR–EBRT^[4].

Moreover, recent advances in the development of LDR Brachytherapy, such as 4D Brachytherapy, mean that the treatment is now available as a one-stage implant technique that can normally be performed within 45 minutes. Improved dosimetry and clinical outcomes together with reduced side effects have been demonstrated over traditional two-stage approaches.

Saheed Rashid, managing director, BXTAccleyon, comments: “While the importance of men and their families researching all the treatment options available to them and discussing these with their consultant must be emphasised, there is an increasing body of evidence to suggest that, of the curative-intent treatment options, Low-Dose-Rate Brachytherapy as a mono- or combination therapy, has favourable outcomes and fewer adverse side effects.

“As a treatment, this option has been proven for over 25 years, and advancements such as 4D brachytherapy and NHS England supported toxicity barriers have further improved the patient experience.”

ENDS

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^[1] Prognostic Value of Biochemical Recurrence Following Treatment with Curative Intent for Prostate Cancer: A Systematic Review, European Urology, Volume 75, Issue 6, June 2019.

^[2] Time Course and Accumulated Risk of Severe Urinary Adverse Events After High-Versus Low-Dose-Rate Prostate Brachytherapy With or Without External Beam Radiation Therapy, Jonathan D. Tward et al, International Journal of Radiation Oncology, June 2016

^[3] Dosimetry of local failure with single dose 19 Gy high-dose-rate brachytherapy for prostate cancer, Shreya Armstrong ⇑, Yatman Tsang, Gerry Lowe, Hannah Tharmalingam, Roberto Alonzi, Peter Ostler, Robert Hughes, Peter Hoskin, Radiotherapy and Oncology 157 (2021) 93–98 

^[4] A comparison of outcomes for patients with intermediate and high risk prostate cancer treated with low dose rate and high dose rate brachytherapy in combination with external beam radiotherapy, F. Slevin et al, Clinical and Translational Radiation Oncology 20 (2020) 1–8