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Extent and predictors of grade upgrading and downgrading in an Australian cohort according to the new prostate cancer grade groupings |
Kerri Beckmanna,b,*(),Michael O’Callaghanc,d,Andrew Vincentd,Penelope Cohene,Martin Borgf,David Rodera,Sue Evansg,Jeremy Millarg,Kim Morettia,d
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a Cancer Research Institute, School of Health Sciences, University of South Australia, Adelaide, Australia b School of Cancer and Pharmaceutical Sciences, King's College London, London, UK c Flinders Medical Centre, Urology Unit, Adelaide, Australia d School of Medicine, University of Adelaide, Adelaide, Australia e SA Pathology, Health SA, Adelaide, South Australia, Australia f Genesis Care, University of Adelaide, Adelaide, Australia g Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia |
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Abstract Object: To determine the extent and impact of upgrading and downgrading among men who underwent radical prostatectomy (RP) according to new grade groupings and to identify predictors of upgrading from biopsy grade Group I and II, and downgrading to grade Group I, in a community setting. Methods: Study participants included 2279 men with non-metastatic prostate cancer diagnosed 2006-2015 who underwent prostatectomy, from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. Extent of up- or down-grading was assessed by comparing biopsy and prostatectomy grade groupings. Risk of biochemical recurrence (BCR) with upgrading was assessed using multivariable competing risk regression. Binomial logistic regression was used to identify pre-treatment predictors of upgrading from grade Groups I and II, and risk group reclassification among men with low risk disease. Results: Upgrading occurred in 35% of cases, while downgrading occurred in 13% of cases. Sixty percent with grade Group I disease were upgraded following prostatectomy. Upgrading from grade Group I was associated with greater risk of BCR compared with concordant grading (Hazard ratio: 3.1, 95% confidence interval: 1.7-6.0). Older age, higher prostate-specific antigen levels (PSA), fewer biopsy cores, higher number of positive cores and more recent diagnosis predicted upgrading from grade Group I, while higher PSA and clinical stage predicted upgrading from grade Group II. No clinical risk factors for reclassification were identified. Conclusion: Biopsy sampling errors may play an important role in upgrading from grade Group I. Improved clinical assessment of grade is needed to encourage greater uptake of active surveillance.
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Received: 02 May 2018
Available online: 07 March 2019
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Corresponding Authors:
Kerri Beckmann
E-mail: kerri.beckmann@unisa.edu.au
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Characteristic | Biopsy grade grouping | p-Valuea | Grade I | Grade II | Grade III | Grade IV | Grade V | Gleason pattern | 3 + 3 | 3 + 4 | 4 + 3 | 8 | 9-10 | | N = 2272 | Total, n (%) | 762 (34) | 821 (36) | 417 (18) | 193 (9) | 79 (3) | | Clinical characteristics | Age, year (mean ± SD) | 61 ± 7 | 63 ± 6 | 64 ± 7 | 65 ± 5 | 66 ± 5 | <0.001 | PSA, ng/mL (IQR) | 7 (5-9) | 7 (5-10) | 8 (6-10) | 7 (6-11) | 8 (6-13) | <0.001 | Public patient, n (%) | 264 (35) | 243 (30) | 100 (24) | 62 (32) | 27 (34) | 0.06 | No. biopsy core (mean ± SD) | 13 ± 6 | 13 ± 6 | 14 ± 5 | 14 ± 7 | 14 ± 7 | 0.08 | Re-biopsyb rate, n (%) | 123 (16) | 73 (9) | 37 (9) | 23 (12) | 4 (5) | <0.001 | Outcomes | PCa deathsc, n (%) | 3 (0.5) | 4 (0.7) | 3 (1.1) | 6 (4.3) | 4 (9.5) | <0.001 | Other deathsc, n (%) | 17 (3) | 18 (3) | 9 (3) | 10 (7) | 2 (5) | 0.05 | Biochemical recurrenced, n (%) | 59 (10) | 105 (19) | 89 (38) | 54 (43) | 22 (56) | <0.001 |
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Cohort characteristics by biopsy grade (new grade groupings).
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Primary RP cases, n=2272 | Biopsy grade grouping | Grade I (3+3) | Grade II (3+4) | Grade III (4+3) | Grade IV (8) | Grade V (9-10) | Total | n = 762 | n = 821 | n = 417 | n = 193 | n = 79 | Grade I (3+3) | 306 (40) | 68 (8) | 4 (1) | 2 (1) | 0 | | Grade II (3+4) | 386 (51) | 522 (64) | 113 (27) | 22 (11) | 4 (5) | | Grade III (4+3) | 58 (8) | 198 (24) | 227 (54) | 74 (38) | 8 (10) | | Grade IV (8) | 8 (1) | 18 (2) | 41 (10) | 60 (31) | 10 (13) | | Grade V (9-10) | 4 (1) | 15 (2) | 32 (8) | 35 (18) | 57 (72) | | Total upgraded | 456 (60) | 231 (28) | 73 (18) | 35 (18) | 0 (0) | 795 (35) | Total downgraded | 0 (0) | 68 (8) | 117 (28) | 98 (51) | 22 (28) | 305 (13) |
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Upgrading/downgrading of grade groupings among men who underwent radical prostatectomy, n (%).
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The crude cumulative incidence of biochemical recurrence following prostatectomy for men classified who were subsequently upgraded or downgraded in final surgical pathology.
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Grade category | SHR | 95% CI | p-Value | Concordant BX- and RP-grade Group I | 1.0 | - | - | Upgraded from BX-grade Group I | 3.1 | 1.7-6.0 | <0.001 | Concordant BX- and RP-grade Group II | 3.6 | 1.9-6.9 | <0.001 | Upgraded from BX-grade Group II | 9.4 | 5.0-17.9 | <0.001 | Concordant BX- and RP-grade Group III | 11.8 | 6.1-22.6 | <0.001 |
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Risk of biochemical recurrence upgraded cases relative to concordant grade Group I.
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Factors | Grade Group I (n = 735) | Grade Group II (n = 797) | No. of upgraded/total | Adj. ORa | 95% CI | p-Value | No. of upgraded/total | Adj. ORa | 95% CI | p-Value | Age at diagnosis (year) | <55 | 80/139 | 1.2 | 0.7-1.9 | 0.45 | 22/91 | 0.8 | 0.4-1.4 | 0.35 | 55-59 | 93/166 | 1.1 | 0.7-1.8 | 0.58 | 34/126 | 0.9 | 0.6-1.6 | 0.76 | 60-64 | 104/195 | 1.0 | - | - | 56/209 | 1.0 | - | - | 65-69 | 109/162 | 1.7 | 1.1-2.7 | 0.03 | 60/232 | 0.9 | 0.6-1.4 | 0.58 | 70+ | 52/73 | 2.0 | 1.1-3.7 | 0.02 | 50/139 | 1.5 | 0.9-2.4 | 0.10 | Pre-treatment PSA ng/mL | <10 | 328/570 | 1.0 | - | - | 135/538 | 1.0 | - | - | 10-19.9 | 73/107 | 1.6 | 1.0-2.6 | 0.04 | 46/134 | 1.6 | 1.1-2.1 | 0.02 | ≥20 | 12/20 | 1.5 | 0.6-4.0 | 0.41 | 13/29 | 2.5 | 1.2-6.6 | 0.02 | Not reported | 38/58 | 1.1 | 0.5-2.1 | 0.87 | 28/96 | 1.4 | 0.8-2.3 | 0.22 | Clinical T stage | ≤T2a | 179/318 | 1.0 | - | - | 60/247 | 1.0 | - | - | T2b/c | 144/225 | 1.0 | 0.7-1.5 | 0.99 | 97/324 | 1.4 | 1.0-2.9 | 0.08 | T3 | - | - | - | - | 13/23 | 5.1 | 2.0-12.9 | 0.001 | Not reported | 115/192 | 1.0 | 0.7-1.6 | 0.81 | 52/203 | 1.1 | 0.7-1.7 | 0.74 | Peri-neural invasion | No evidence | 302/503 | 1.0 | - | - | 128/483 | 1.0 | - | - | Yes | 48/79 | 1.0 | 0.6-1.7 | 0.94 | 71/248 | 1.2 | 0.8-1.6 | 0.51 | Not reported | 96/153 | 1.4 | 0.9-2.1 | 0.11 | 23/66 | 1.7 | 0.9-3.0 | 0.09 | Biopsy procedure | TRUS | 425/707 | 1.0 | - | - | 211/247 | 1.0 | - | - | Trans-perineal | 13/28 | 0.8 | 0.5-1.4 | 0.40 | 11/32 | 1.2 | 0.7-1.9 | 0.52 | No. of biopsy cores | ≤6 | 59/97 | 1.0 | - | - | 16/55 | 1.0 | - | - | 7-11 | 110/204 | 0.7 | 0.4-1.3 | 0.24 | 66/225 | 1.2 | 0.6-2.3 | 0.68 | 12-14 | 174/270 | 0.8 | 0.4-1.3 | 0.30 | 82/304 | 1.0 | 0.5-2.1 | 0.95 | 15-18 | 62/99 | 0.5 | 0.3-1.0 | 0.06 | 31/122 | 1.0 | 0.4-2.2 | 0.95 | ≥19 | 33/65 | 0.3 | 0.1-0.6 | 0.005 | 27/91 | 1.1 | 0.4-2.7 | 0.91 | No. of positive cores | ≤2 | 163/309 | 1.0 | - | - | 35/136 | 1.0 | - | - | 3-4 | 125/201 | 1.6 | 1.1-2.4 | 0.02 | 65/230 | 1.1 | 0.7-1.8 | 0.71 | 5-7 | 106/168 | 1.5 | 1.0-2.3 | 0.07 | 77/267 | 1.1 | 0.7-1.8 | 0.69 | ≥8 | 44/59 | 2.3 | 1.2-4.7 | 0.02 | 24/164 | 0.9 | 0.5-1.6 | 0.68 | Diagnosis year (continuous) | - | 1.2 | 1.1-1.3 | 0.001 | - | 1.0 | 0.9-1.0 | 0.43 |
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Factors predicting risk of upgrading from biopsy grade Group I and grade Group II.
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Factors (Low risk disease only n = 409) | No. reclassified/total | Adj. ORa | 95% CI | p-Value | Age at diagnosis (cont.) | 60/409 | 1.0 | 1.0-1.1 | 0.80 | Year diagnosis (cont.) | - | 1.0 | 0.9-1.1 | 0.54 | Pre-treatment PSA ng/mL (cont.) | - | 1.1 | 1.0-1.3 | 0.11 | Grade Group | - I | 25/260 | 1.0 | - | - | - II | 35/149 | 2.9 | 1.6-5.3 | | Clinical stage | - T1c | 18/156 | 1.0 | - | - | - T2 | 42/253 | 1.5 | 0.8-2.9 | 0.22 | No. cores taken (cont) | - | 1.0 | 1.0-1.1 | 0.58 | Percent positive cores | - <10 | 8/91 | 1.0 | - | - | - 10 to <15 | 13/81 | 1.7 | 0.7-4.6 | 0.26 | - 15 to <20 | 22/100 | 2.1 | 1.0-5.2 | 0.11 | - 20 to <25 | 12/64 | 1.8 | 0.6-4.8 | 0.27 | - 25 or more | 5/73 | 0.5 | 0.1-1.5 | 0.20 |
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Factors associated with upgrading leading to reclassification of risk category among men with low risk prostate cancer at biopsy.
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