Background
Multiparametric magnetic resonance imaging (mpMRI) has improved risk stratification for suspected prostate cancer in patients following prior biopsy. However, not all significant cancers are detected by mpMRI. The PICTURE study provides the ideal opportunity to investigate cancer undetected by mpMRI owing to the use of 5 mm transperineal template mapping (TTPM) biopsy.

Objective
To summarise attributes of cancers systematically undetected by mpMRI in patients with prior biopsy.

Design, setting, and participants
PICTURE was a paired-cohort confirmatory study in which men requiring repeat biopsy underwent mpMRI followed by TTPM biopsy.

Outcome measurements and statistical analysis
Attributes were compared between cancers detected and undetected by mpMRI at the patient level. Four predefined histopathological thresholds were used as the target condition for TTPM biopsy. Application of prostate-specific antigen density (PSAD) was explored.

Results and limitations
When nonsuspicious mpMRI was defined as Likert score 1–2, 2.9% of patients (3/103; 95% confidence interval [CI] 0.6–8.3%) with definition 1 disease (Gleason ≥ 4 + 3 of any length or maximum cancer core length [MCCL] ≥ 6 mm of any grade) had their cancer not detected by mpMRI. This proportion was 6.5% (11/168; 95% CI 3.3–11%) for definition 2 disease (Gleason ≥ 3 + 4 of any length or MCCL ≥ 4 mm of any grade), 4.8% (7/146; 95% CI 2.0–9.6%) for any amount of Gleason ≥ 3 + 4 cancer, and 9.3% (20/215; 95% CI 5.8–14%) for any cancer. Definition 1 cancers undetected by mpMRI had lower overall Gleason score (p = 0.02) and maximum Gleason score (p = 0.01) compared to cancers detected by mpMRI. Prostate cancers undetected by mpMRI had shorter MCCL than cancers detected by mpMRI for every cancer threshold: definition 1, 6 versus 8 mm (p = 0.02); definition 2, 5 versus 6 mm (p = 0.04); any Gleason ≥ 3 + 4, 5 versus 6 mm (p = 0.03); and any cancer, 3 versus 5 mm (p = 0.0009). A theoretical PSAD threshold of 0.15 ng/ml/ml reduced the proportion of patients with undetected disease on nonsuspicious mpMRI to 0% (0/105; 95% CI 0–3.5%) for definition 1, 0.58% (1/171; 95% CI 0.01–3.2%) for definition 2, and 0% (0/146) for any Gleason ≥ 3 + 4.

Conclusions
Few significant cancers are undetected by mpMRI in patients requiring repeat prostate biopsy. Undetected tumours are of lower overall and maximum Gleason grade and shorter cancer length compared to cancers detected by mpMRI.

Patient summary
In patients with a previous prostate biopsy, magnetic resonance imaging (MRI) overlooks few prostate cancers, and these tend to be smaller and less aggressive than cancer that is detected.