Table 2.
Participants summarised by mutation status, PSA summary data, and PPV of PSA and biopsy
| Total cohort (n=962*) | MLH1 carriers (n=204) | MLH1 non-carrier controls (n=199) | MSH2 carriers (n=305) | MSH2 non-carrier controls (n=210) | MSH6 carriers (n=135) | MSH6 non-carrier controls (n=177) | |||
|---|---|---|---|---|---|---|---|---|---|
| Total PSA screenings done at baseline | 958 | 203 | 199 | 303 | 210 | 134 | 177 | ||
| Median PSA concentrations, ng/mL | 0·8 (0·6 to 1·4) | 0·9 (0·6 to 1·4) | 0·8 (0·6 to 1·4) | 0·8 (0·6 to 1·4) | 0·9 (0·6 to 1·5) | 0·8 (0·6 to 1·4) | 0·8 (0·5 to 1·4) | ||
| PSA concentration >3·0 ng/mL | 56 (6%) | 11 (5%) | 10 (5%) | 27 (9%) | 7 (3%) | 5 (4%) | 4 (2%) | ||
| Biopsies† | 35 (4%) | 6 (3%) | 5 (3%) | 18 (6%) | 3 (1%) | 5 (4%) | 2 (1%) | ||
| Benign tumour | 14 | 5 | 4 | 5 | 2 | 0 | 2 | ||
| ASAP or HGPIN | 3 | 1 | 1 | 0 | 0 | 1 | 0 | ||
| Malignant tumour—ie, prostate cancer incidence with PSA >3·0 ng/mL | 18 (1·9% [1·1 to 2·9]) | 0 | 0 | 13 (4·3% [2·3 to 7·2]) | 1 (0·5% [0·0 to 2·6]) | 4 (3·0% [0·8 to 7·4]) | 0 | ||
| Difference between carriers and non-carrier controls | NA | 0 | .. | 3·8% (1·3 to 6·2) | .. | 3·0% (0·1 to 5·8) | .. | ||
| p value | NA | .. | 0·011 | .. | 0·034 | .. | |||
| Clinically significant prostate cancer incidence with PSA >3·0 ng/mL | 14 (1·5% [0·8 to 2·4]) | 0 | 0 | 11 (3·6% [1·8 to 6·4]) | 0 | 3 (2·2%[0·5 to 6·4]) | 0 | ||
| Difference between carriers and non-carrier controls | NA | NA | .. | 3·6% (1·5 to 5·7) | .. | 2·2% [−0·3 to 4·7) | .. | ||
| p value | NA | NA | .. | 0·0037 | .. | 0·080 | .. | ||
| PPV of biopsy‡ | 51·4% (34·0 to 68·6) | 0 | 0 | 72·2% (46·5 to 90·3) | 33·3% (0·8 to 90·6) | 80·0% (28·4 to 99·5) | 0 | ||
| Difference between carriers and non-carrier controls | NA | 0 | .. | 38·9% (18·3 to 96·1) | .. | 80·0% (44·9 to 115·1) | .. | ||
| p value | NA | NA | .. | 0·25 | .. | 0·14 | .. | ||
| PPV of PSA >3·0 ng/mL requiring action§ | 32·1% (20·3 to 46·0) | 0 | 0 | 48·1% (28·7 to 68·1) | 14·3% (0·4 to 57·9) | 80·0% (28·4 to 99·5) | 0 | ||
| Difference between carriers and non-carrier controls | NA | 0 | .. | 33·9% (1·8 to 65·9) | .. | 80·0% (44·9 to 115·1) | .. | ||
| p value | NA | NA | .. | 0·20 | .. | 0·048 | .. | ||
Data are n (%), median (IQR), n with incidence and 95% CI in parentheses, or incidence with 95% CI in parentheses. ASAP=atypical small acinar proliferation. HGPIN=high-grade prostate intraepithelial neoplasia. NA=not applicable. PPV=positive predictive value.
BRCA1 and BRCA2 non-carrier controls were included in every non-carrier control group, but only counted once in the total cohort number; therefore, the sum of each genetic cohort does not equal the total.
Not including off-protocol biopsies (in participants with PSA <3·0 ng/mL).
PPV of biopsy is number of cancers diagnosed divided by the number of biopsies performed.
PPV of PSA >3ng/mL requiring action is number of cancers diagnosed divided by number of PSA readings of >3·0 ng/mL.