A study by the Mayo Clinic group. This study examined the acute CTCAE reported by 55 patients (PRO-CTCAE) with high-risk or unfavorable intermediate-risk prostate cancer treated by PBT, and the acute CTCAE reported by investigators (IR-CTCAE) at baseline, during RT and post-RT. 11 PRO-CTCAE questions assessed gastrointestinal (GI), genitourinary (GU), or erectile function side effects. This study found that IR-CTCAE underestimated diarrhea compared to PRO-CTCAE at the end of treatment (EOT), with a 28% rate of underestimation (11% by ≥ 2 toxicity grades). Similarly, urinary tract pain was underestimated in 45% of cases (17% by ≥ 2 grades) at EOT. The degree of interference with daily activities was consistently overestimated by investigators at all time points (45%-85%). Similarly, erectile dysfunction showed a 36-56% rate of discordance by ≥ 2 toxicity grades. This study presented a low agreement between IR-CTCAE and PRO-CTCAE in the setting of proton therapy for prostate cancer, and the authors recommended using PROs continuously.