Erislandy Lara has shattered Michael Zerafa's dream of winning a world title for his ailing sister with the Cuban-American emphatically retaining his WBA middleweight crown in Las Vegas.

Fighting on the blockbuster Tim Tszyu-Sebastian Fundora card, Zerafa's night ended in the second round after he was sent tumbling to the canvas at T-Mobile Arena.

The Victorian had dedicated the fight to older sister Michelle, who had surprised Zerafa by being ringside despite undergoing treatment for breast cancer.

Lara held the strap since 2021 but hadn't fought since May 2022 but the 40-year-old southpaw showed he still had the slick moves that had made him a champion.

Zerafa, 32, had also been out of the ring for 16 months but enlisted four-division Filipino superstar Nonito Donaire as his trainer for the campaign and he arrived in the fight capital looking in the best shape of his career.

Both fighters felt their way through the opening round but Lara (30-4, 18KO) upped the stakes after coming out for the second.

He unsettled Zerafa (31-5, 19KO) with a straight left and, sensing his opening, unleashed on his rival with a devastating right-left combination with Zerafa unable to continue.

A heavily dazed Zerafa waved his arms in defeat as TV footage captured his sister praying for her brother to be OK.

Zerafa was with medical staff and unable to speak with media post-fight while Lara said he had proved doubters wrong, with a question mark over his age and time out of the ring.

Lara said he knew from the first round he had Zerafa's measure.

"I've always said that I only need one or two rounds to size up my opponent and I knew I had him from the very first round," the Florida-based boxer said.

"That left hand shot was just a matter of time.

"Rust, what rust? I've worked my f***ing a*** off in training because I know that all of these fighters are coming for my title.

"By staying ready you don't have to get ready."

The crushing defeat leaves Zerafa's career at a crossroad.

He is involved in court action after an an ugly split with his trainer Sam Labruna and is unlikely to get another shot on the main stage.