Spaniard Prades (Caja Rural Seguros-RGA) triumphed atop Manayunk Wall ahead of second-placed American Travis McCabe (Holowesko-Citadel) and third-placed Marco Canola (UnitedHealthcare) of Italy.
Prades, quoted on cyclingnews.com, said: "I knew coming into the last lap that I could win this race.
"When we caught the breakaway, I had my team-mates at the front and I told them that I knew that I could do this today.
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"I needed to be in the top 10 going into the climb; I was, and I knew that I could win."
The assistance of Boels-Dolmans team-mate Karol-Ann Canuel of Canada helped American Guarnier claim her victory in a race that saw Italy's Elisa Longo Borghini (Wiggle High5) finish second and Belarus' Alena Amialiusik (Canyon-SRAM) third.
"Karol-Ann was amazing and led me up the climb," said Guarnier, the current UCI Women's WorldTour leader.
"It's a surprise win because I didn't expect to win today. I went with a kick at the end, and ooh la la, no one followed me.
"I'll defend this jersey one day at a time."
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