Supergirl ending with season 6 likely means that Crisis On Infinite Earths was the last Arrowverse crossover for the Girl of Steel. The final season of Supergirl will premiere in midseason 2021 on The CW instead of premiering earlier in 2021 like The Flash. The stars and producers of Supergirl have hit social media to confirm that season 6 will indeed be the end, and Benoist encouragingly promises "one helluva final season" - but sadly, Supergirl season 6 may not include one final team-up with the Kryptonian heroine and her super friends in the Arrowverse.
The Flash and Arrow pioneered the Arrowerse crossovers but Supergirl made them extra special. In the years before Crisis, Supergirl lived in a different dimension of the DCTV Multiverse, Earth-38, and, in Supergirl's first season, the show was even on another network, CBS. Barry Allen (Grant Gustin) crossing over to Supergirl in season 1 was a jolt of electricity that caused fervent fan demand for Kara Danvers and her world to officially become part of the Arrowverse. That happened when Supergirl moved to The CW in season 2. Kara and Barry also had a delightful musical crossover together titled "Duet", showcasing their song-and-dance chops. Excitingly, Supergirl's leap to The CW opened the door for the Girl of Steel to take a central role as part of the Arrowverse's "Trinity" with The Flash and Green Arrow (Stephen Amell).
In fact, Supergirl became increasingly important to the annual Arrowverse crossovers. The immensely powerful Kara Zor-El was a sensation among her fellow superheroes when she crossed over to The Flash, Arrow, and Legends of Tomorrow's Earth-1 to battle the alien Dominators in 2016's Invasion! event. 2017's Crisis On Earth-X was literally about stealing Supergirl's heart when Nazi doppelgangers of the heroes attacked Earth-1 and showed fans the thrilling battle between Supergirl and her double, Overgirl. Kara was also crucial to 2018's Elseworlds since her friendship is what brought Batwoman (Ruby Rose) into the Arrowverse. 2019/2020's Crisis On Infinite Earths cemented Supergirl as one of the most important heroes in the Multiverse; Kara was proclaimed as the Paragon of Hope and she became a founding member of the Justice League after Earth-38 merged with Earth-1 to become Earth-Prime. But after Crisis ended, Supergirl returned to her home of National City and she had no further on-screen interactions with her fellow heroes.
After the herculean task of producing Crisis On Infinite Earths, the Arrowverse understandably decided to scale back on crossovers, and this was well before the COVID-19 pandemic drastically altered how films and TV series will be produced going forward. With the necessary safety protocols in place, simply producing a TV series is now beset with difficult new challenges, making a massive crossover event involving multiple superheroes appearing together (with the necessary amount of crew working behind the camera supporting them) inadvisable and unlikely to occur in the near future.
Presently, the only upcoming team-up known to be in the cards will see the new Batwoman (Javicia Leslie) team up with Superman (Tyler Hoechlin), which may or may not include Supergirl in some capacity. Meanwhile, Supergirl has its 20-episode final season to mount, and there will naturally be extra precautions expected to be taken for Melissa Benoist, who will be a new mother during Supergirl season 6.
All of this means that, barring a surprise or a radical change in the world in the upcoming 2021-2022 TV season, Crisis On Infinite Earths will probably stand as Supergirl's last hurrah in terms of Arrowverse mega-crossover team-ups. It's true that Crisis was so gargantuan that it's hard to imagine an event that could go bigger, but if Supergirl does join in a team-up at some point in season 6, it will probably much more intimate, like her "Duet" with Barry was. This is sad for fans, especially considering that at this point, the Justice League that assembled at the end of Crisis hasn't even had one adventure together as a team, and it's also hard to imagine what the Arrowverse will look like without Supergirl as a shining beacon at its center.