Uran was 59 seconds off the overall lead in sixth, while Roche spent three days in the leader’s jersey.
The Colombian’s teammate Hugh Carthy and Victor de la Parte (CCC Team) also retired after the crash with 80 kilometres remaining. De La Parte was 13th in GC.
Riders from Lotto Soudal, Deceuninck-Quick Step and Jumbo-Visma were also reportedly caught up in the melee.
Astana’s Miguel Angel Lopez held a 14-second lead over Primoz Roglic (Jumbo-Visma) ahead of the race’s second summit finish.
"It feels a bit numb, and you look at the demeanour of the riders as well – they’re very much pondering what’s happened to others. When an accident like that happens, and it was a big one, it alters the mood entirely of a group who are essentially a band of brothers that take this sport around the world."
- Carlton Kirby, Eurosport UK cycling commentator
"It’s such a disappointment. These were riders who could have featured in GC, it’s a massive blow for the race and the teams."
- Brian Smith, Eurosport UK cycling expert
"It's a huge blow for EF Education First, and a sad way for Nico Roche to end his race. That's only his second DNF in 22 Grand Tours - and his first in nine Vueltas."
- Felix Lowe, Eurosport UK chief cycling journalist
"Rigoberto Uran and Nicolas Roche were both inside a minute of the race lead and losing them is huge for the race. Roche has been a star of the opening week and domestic audiences would surely have been looking forward to seeing how he goes for the remainder of the tour. Hugh Carthy too is a massive loss from a UK perspective – the 25-year-old is an exciting rider to watch and would have really energised this race… as well as giving plenty of entertainingly droll interviews. We can only hope that none of their injuries are too serious."
- Tom Bennett, Eurosport UK cycling editor