Table 1.
Patient characteristics by cohort for the 3871 individuals included in the GWAS meta-analysis
| Characteristics | All cohorts | RAPPER | RADIOGEN | GenePARE | UGhent | CCI-BT | CCI-EBRT |
|---|---|---|---|---|---|---|---|
| (n = 3871) | (n = 2010) | (n = 658) | (n = 492) | (n = 311) | (n = 252) | (n = 148) | |
| Age at treatment, median (range), y* | 68 (43–86) | 68 (48–84) | 72 (47–86) | 65 (43–85) | 65 (49–81) | 65 (45–79) | 68 (45–82) |
| NCCN risk group, No. (%) | |||||||
| Very low | 545 (14.1) | 133 (6.6) | 100 (15.2) | 172 (35.0) | 43 (13.8)† | 89 (35.3) | 8 (5.4) |
| Low | 258 (6.7) | 82 (4.1) | 23 (3.5) | 61 (12.4) | 21 (6.8) | 68 (27.0) | 3 (2.0) |
| Intermediate | 2635 (68.1) | 1566 (77.9) | 447 (67.9) | 232 (47.2) | 173 (55.6) | 95 (37.7) | 122 (82.4) |
| High or very high | 410 (10.6) | 229 (11.4) | 82 (12.5) | 27 (5.5) | 57 (18.4) | 0 | 15 (10.1) |
| Not available | 23 (0.6) | 0 | 6 (0.9) | 0 | 17 (5.5) | 0 | 0 |
| Stage at diagnosis, No. (%) | |||||||
| T1a–c, T1x | 1443 (37.3) | 709 (35.3) | 226 (34.3) | 249 (50.6) | 101 (32.5) | 119 (47.2) | 38 (25.7) |
| T2a–c, T2x | 2020 (52.2) | 1084 (53.9) | 362 (55.0) | 227 (46.1) | 126 (40.5) | 132 (52.4) | 89 (60.1) |
| T3a–c, T3x | 305 (7.9) | 182 (9.1) | 54 (2.7) | 16 (3.3) | 37 (11.9) | 0 | 16 (10.8) |
| T4 | 14 (0.4) | 0 | 7 (1.1) | 0 | 6 (1.9) | 0 | 1 (0.7) |
| Not available | 89 (2.3) | 35 (1.7) | 9 (1.4) | 0 | 41 (13.2) | 1 (0.4) | 4 (2.7) |
| Gleason at diagnosis, No. (%) | |||||||
| ≤6 | 1702 (44.0) | 605 (30.1) | 403 (61.2) | 310 (63.0) | 142 (45.7) | 212 (84.1) | 30 (20.3) |
| 7 | 1653 (42.7) | 1109 (55.2) | 176 (26.8) | 124 (25.2) | 107 (34.4) | 40 (15.9) | 97 (65.5) |
| ≥8 | 265 (6.8) | 56 (2.8) | 70 (10.6) | 58 (11.8) | 60 (19.3) | 0 | 21 (14.2) |
| Not available | 251 (6.5) | 240 (11.9) | 9 (1.4) | 0 | 2 (0.6) | 0 | 0 |
| Pretreatment PSA, median (range) | 8.9 (0–236.0) | 10.1 (0.6–33.5) | 9.7 (0.6–236.0) | 6.2 (0.6–124.0) | 6.6 (0–150.0)‡ | 6.3 (0.5–16.0) | 10.9 (1.4–80.0) |
| Radical prostatectomy, No. (%)* | |||||||
| Yes | 225 (5.8) | 0 | 128 (29.5) | 0 | 97 (31.2) | 0 | 0 |
| No | 3646 (94.2) | 2010 (100) | 530 (80.5) | 492 (100) | 214 (68.8) | 252 (100) | 148 (100) |
| Androgen-deprivation therapy, No. (%)* | |||||||
| Yes | 3047 (78.7) | 2010 (100) | 463 (70.4) | 248 (50.4) | 198 (63.7) | 55 (21.8) | 73 (49.3) |
| No | 824 (21.3) | 0 | 195 (29.6) | 244 (49.6) | 113 (36.3) | 197 (78.2) | 75 (50.7) |
| Type of radiotherapy, No. (%) | |||||||
| 3D-CRT | 895 (25.4) | 237 (11.8) | 658 (100) | 0 | 0 | 0 | 0 |
| IMRT | 2239 (57.8) | 1773 (88.2) | 0 | 7 (1.4) | 311 (100) | 0 | 148 (100) |
| Brachytherapy | 534 (13.8) | 0 | 0 | 282 (57.3) | 0 | 252 (100) | 0 |
| Brachytherapy + EBRT | 203 (5.2) | 0 | 0 | 203 (41.3) | 0 | 0 | 0 |
| Total BED§, median (range)* | 123 (52–292) | 120 (107–123) | 123 (57–127) | 192 (52–269) | 136 (124–136) | 158 (80–292) | 121 (112–134) |
| No. (%) with grade 2 or worse toxicity | |||||||
| Increased urinary frequency‖ | 436 (11.5) | 219 (10.9) | 60 (9.1) | 113 (24.6) | 8 (2.6)¶ | NA# | 15 (10.1) |
| Decreased urinary stream** | 345 (9.9) | 159 (7.9) | 27 (4.1) | 125 (27.2) | NA†† | NA# | 12 (8.1) |
| Hematuria‡‡ | 333 (9.2) | 182 (9.1) | 66 (10.0) | 62 (12.6) | 17 (5.5)¶ | NA§§ | 6 (4.1) |
| Rectal bleeding‖‖ | 423 (12.5) | 273 (13.6) | 79 (12.0) | NA¶¶ | 6 (1.9)¶ | 40 (15.9) | 25 (16.9) |
Age at treatment, radical prostatectomy, androgen-deprivation therapy, and total BED were included as covariates in the GWAS meta-analysis. BED = biological effective dose; CCI-BT = Cross Cancer Institute–Brachytherapy; CC-EBRT = Cross Cancer Institute–External Beam Radiotherapy; 3D-CRT = three-dimensional conformal radiotherapy; EBRT = external beam radiotherapy (either 3D-CRT or IMRT); GenePARE = Genetic Predictors of Adverse Radiotherapy Effects; GWAS = genome-wide association study; IMRT = intensity-modulated radiotherapy; NCCN = National Comprehensive Cancer Network; PSA = prostate specific antigen; RAPPER = Radiogenomics: Assessment of Polymorphisms for Predicting the Effects of Radiotherapy; UGhent = University of Ghent.
NCCN risk group in the UGhent cohort was defined using preradiotherapy PSA rather than PSA at diagnosis.
PSA measurement is pre-radiotherapy but postprostatectomy in patients who received prior prostatectomy.
Total BED was calculated using an α to β ratio of 3 following Ho et al. (27).
Increased urinary frequency was evaluable in 3782 participants with available baseline and follow-up data (2010 in RAPPER, 658 in RADIOGEN, 459 in GenePARE, 303 in UGhent, and 148 in CCI-EBRT).
Follow-up in UGhent was from 18 months to 30 months as opposed to 6 months to 5 years in all other studies.
Increased urinary frequency and decreased urinary stream were not analyzed in CCI-BT because assessments were not conducted at regular intervals.
Decreased urinary stream was evaluable in 3470 participants with available baseline and follow-up data (2010 in RAPPER, 658 in RADIOGEN, 459 in GenePARE, and 148 in CCI-EBRT).
Decreased urinary stream was not assessed in UGhent.
Hematuria was evaluable in 3619 participants with available baseline and follow-up data (2010 in RAPPER, 658 in RADIOGEN, 492 in GenePARE, 311 in UGhent, and 148 in CCI-EBRT).
Hematuria was not assessed in CCI-BT.
Rectal bleeding was evaluable in 3379 participants with available baseline and follow-up data (2010 in RAPPER, 658 in RADIOGEN, 311 in UGhent, 252 in CCI-BT, and 148 in CCI-EBRT).
Rectal bleeding was assigned a single grade in GenePARE using information across all follow-up assessments, so this outcome was not available for analysis.