Pain-Free TRUS B: A phase 3 double-blind placebo-controlled randomized trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasound-guided prostate biopsy (ANZUP 1501).

To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasound guided prostate biopsies (TRUSB) improved pain and other aspects of the experience.

Multicentre, placebo-controlled, double-blind, randomised phase 3 trial involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3mL of methoxyflurane, or 3mL of 0.9% saline plus one drop of methoxyflurane to preserve blinding. Primary outcome was the pain score (0 to 10) reported by the participant after fifteen minutes. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events.

Pain scores 15 minutes after TRUSB were 2.51 (SE 0.22) in those assigned methoxyflurane versus 2.82 (SE 0.22) for placebo (difference 0.31, 95% CI -0.75 to 0.14; p=0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03, p=0.035, adj p=0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08, p=0.021, adj p=0.053), and willingness to undergo repeat biopsies (OR 1.67, 95% CI 1.12-2.49, p=0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21 to 2.07, p<0.001, adj p<0.001) and dizziness (difference +1.78, 95% CI 1.31 to 2.24, p<0.001, adj p<0.001) than placebo. There was no significant difference in the number of ≥ grade three adverse events.

We found no evidence that methoxyflurane improved pain scores at 15 minutes, however improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

BJU international. 2021 Jul 17 [Epub ahead of print]

Dickon Hayne, Jeremy Grummet, David Espinoza, Steve P McCombie, Venu Chalasani, Kate S Ford, Mark Frydenberg, Peter Gilling, Barbara Gordon, Cynthia Hawks, Alex Konstantatos, Andrew J Martin, Anthony Nixon, Colin O'Brien, Manish I Patel, Shomik Sengupta, Shekib Shahbaz, Shalini Subramaniam, Scott Williams, Henry H Woo, Martin R Stockler, Ian D Davis, Nick Buchan, Australian, New Zealand Urogenital, Prostate Cancer Trials Group (ANZUP)

UWA Medical School, University of Western Australia, Perth, Australia., Alfred Health, Central Clinical School, Monash University, Melbourne, Australia., NHMRC Clinical Trials Centre, Sydney, Australia., Sydney Adventist Hospital, Sydney, Australia., Cabrini Institute, Cabrini Health, Melbourne, Australia., Tauranga Urology Research, Tauranga, New Zealand., Canterbury Urology Research Trust, Christchurch, New Zealand., Cardinal Points Research, Whangarei, New Zealand., Consumer Advisory Panel, Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Sydney, Australia., Discipline of Surgery, University of Sydney, Westmead Hospital, Sydney, Australia., Eastern Health Clinical School, Monash University, Melbourne, Australia., Monash Health, Casey Hospital, Melbourne, Australia., Peter MacCallum Cancer Centre, Melbourne, Australia.