External beam radiotherapy (EBRT) for prostate cancer can be performed with a high dose of 86 Gy; however, one-tenth or more of the patients will develop recurrence. Prostate cancer is mainly multifocal, but a dominant intraprostatic lesion (DIL) is often the site of local recurrence after EBRT. We undertook a systematic review and meta-analysis to clarify whether functional imaging might identify the DIL and whether a RT boost to the DIL might be increased to an ultrahigh dose level of ≥ 90 Gy without increased toxicity. Of 62 selected studies, 13 reported the size of the DIL. The mean of the median DIL volumes was 2.4 cm3 (95% confidence interval, 0.9–4.4 cm3). Eighteen diagnostic studies with 1205 patients evaluated the diagnostic accuracy using multiparametric magnetic resonance imaging for intraprostatic cancer lesions. Evaluating 14,654 prostate segments, the diagnostic accuracy was 77%. Eleven therapeutic studies with 988 patients reported a RT boost for the DIL. The summary boost dose for the DIL was a mean of 89 Gy in 5 studies using intensity modulated RT (calculated as the equivalent dose in 2-Gy fractions) and a mean of 141 Gy in 4 studies using a combination of EBRT and brachytherapy (P = .018, t test). In 1 therapeutic study, 239 patients had a 98% 10-year disease-free survival rate. Many of our therapeutic studies used a boost dose to the DIL of > 90 Gy. The reported boost for DIL is effective and safe.