A new study on Prostate Cancer (PCa) Overall Survival (OS) Outcomes conducted by the Yale School of Medicine, as published by the European Association of Urology, has indicated that low dose rate brachytherapy (LDR-B) boost is associated with better overall survival for men with unfavourable PCa when compared to dose-escalated external-beam radiotherapy (DE-EBRT), despite a decrease in its utilisation. Saheed Rashid, Managing Director, BXT-Accelyon, examines the latest scientific evidence.

Prostate cancer (PCa) remained the second leading cause of cancer death among men in 2015[i]. This is largely attributable to patients with unfavourable PCa (ie. intermediate- and high-risk disease), which is associated with 10-yr survival as low as 25% without treatment[ii].

While the current default position for low risk cancer is active surveillance, when it comes to prostate cancer treatment, the vast majority of younger patients now receive radical prostatectomy – and in 75% of cases this is now via robotic surgery in the UK; with older patients receiving dose escalating External Beam Radiotherapy (DE-EBM).

Yet, as a recent study published in the New England Journal of Medicine[iii] revealed, radical prostatectomy has the greatest impairment of sexual function and urinary continence when compared with other treatment options, including active monitoring and radical radiotherapy with hormones.

Multiple prospective trials of men with unfavourable PCa have shown that the combination of radiation therapy and androgen suppression (AS) improves overall survival (OS) when compared to either treatment alone[iv]. However, these studies did not use dose-escalated external-beam radiation therapy (DE-EBRT), nor brachytherapy – a treatment that has been used to escalate radiation doses beyond those that can be delivered routinely with EBRT.

Until recently, there has been only limited data comparing DE-EBRT and brachytherapy among men with unfavourable PCa.

ASCENDE-RT & Yale School of Medicine Study
A recent ASCENDE-RT study from Canada, comparing AS and whole-pelvis EBRT with either an EBRT boost or a low-dose rate brachytherapy (LDR-B) boost for men with intermediate- and high-risk PCa, demonstrated a 50% decrease in biochemical relapse with the use of LDR-B in conjunction with hormones and whole pelvis radiotherapy when compared to using DE-EBRT with the same treatments in patients randomly assigned to the two forms of treatment.

There was no difference in 7-yr OS, but there was a trend favouring LDR-B boost (85.7% vs 81.5%)[v]. However, at median follow-up of 6.5 yr, ASCENDE-RT had not reached median survival, and if a difference exists, the results may not be available for many years. Therefore, the latest Yale School of Medicine study has analysed the National Cancer Data Base (NCDB) to compare survival outcomes between men treated between 2004 and 2012 with AS and EBRT followed by either EBRT alone or LDR-B boost in a large national cohort.

The study identified 25,038 patients treated with AS and definitive radiation, of whom 20,522 (82%) were treated with DE-EBRT and 4,516 (18%) with EBRT followed by LDR-B boost. During the course of the study, between 2004 and 2012 the proportion of patients receiving LDR-B boost decreased from 29% to 14%, while patients receiving DE-EBRT increased from 71% to 86%.

The study’s findings suggest that men with unfavourable-risk PCa who were selected to undergo LDR-B boost survived longer[vi], stating “LDR-B boost is probably the ideal treatment option for men with unfavourable PCa”. These findings complement results from large randomised trials, supporting the efficacy of LDR-B boost and suggesting that improvements in biochemical control may translate to better OS with additional follow-up.

Despite improved outcomes for LDR-B boost, the patterns of care analysis suggest a decrease in LDR-B boost utilisation between 2004 and 2012, confirming a previous report that showed declines in the use of combined EBRT and brachytherapy boost between 2004 and 2009[vii].

Past investigators have proposed multiple reasons for the decline, including an increase in the number of prostatectomies[viii], increases in reimbursement for other radiation treatments including intensity-modulated radiation[ix], a decrease in brachytherapy training[x], and perception of brachytherapy as a procedure with excessive liability risk[xi].

When analysis of the Yale study affirms that the “optimal treatment [for PCa patients] to prevent the otherwise inevitable progression to castrate-resistant disease and the ensuing cascade of extremely costly palliative interventions, is of paramount concern[xii],” it begs the question: How, when the evidence is overwhelmingly pointing towards the more positive biochemical and survival outcomes brachytherapy offers, can we overcome medical bias towards less favourable treatment options?

[i] SiegelRL,MillerKD,JemalA.Cancerstatistics,2015.CACancerJClin 2015;65:5–29.

[ii] Lu-Yao GL, Albertsen PC, Moore DF, et al. Outcomes of localized prostate cancer following conservative management. JAMA 2009;302:1202–9.

[iii] http://www.nejm.org/doi/full/10.1056/NEJMoa1606221

[iv] See references included: http://www.europeanurology.com/article/S0302-2838(17)30515-8/fulltext

[v] Morris WJ, Tyldesley S, Pai HH, et al. ASCENDE-RT*: a multicenter, randomized trial of dose-escalated external beam radiation thera- py (EBRT-B) versus low-dose-rate brachytherapy (LDR-B) for men with unfavorable-risk localized prostate cancer. J Clin Oncol 2015;33(Suppl 7):3.

[vi] http://www.europeanurology.com/article/S0302-2838(17)30515-8/fulltext

[vii] Martin JM, Handorf EA, Kutikov A, et al. The rise and fall of prostate brachytherapy: use of brachytherapy for the treatment of localized prostate cancer in the National Cancer Data Base. Cancer 2014;120:2114–21.

[viii] Martin JM, Handorf EA, Kutikov A, et al. The rise and fall of prostate brachytherapy: use of brachytherapy for the treatment of localized prostate cancer in the National Cancer Data Base. Cancer 2014;120:2114–21.

[ix] Mitchell JM. Urologists’ use of intensity-modulated radiation ther- apy for prostate cancer. N Engl J Med 2013;369:1629–37.

[x] Compton JJ, Gaspar LE, Shrieve DC, et al. Resident-reported brachy- therapy experience in ACGME-accredited radiation oncology train- ing programs. Brachytherapy 2013;12:622–7.

[xi] Petereit DG, Frank SJ, Viswanathan AN, et al. Brachytherapy: where has it gone? J Clin Oncol 2015;33:980–2.

[xii] http://www.europeanurology.com/article/S0302-2838(17)30589-4/pdf