| Literature DB >> 26943768 |
Biming He1, Rui Chen1, Xu Gao1, Shancheng Ren1, Bo Yang1, Jianguo Hou1, Linhui Wang1, Qing Yang1, Tie Zhou1, Lin Zhao1, Chuanliang Xu1, Yinghao Sun1.
Abstract
The current strategy for the histological assessment of prostate cancer (PCa) is mainly based on the Gleason score (GS). However, 30-40% of patients who undergo radical prostatectomy (RP) are misclassified at biopsy pathologically. Thus, we developed and validated nomograms for the prediction of Gleason score upgrading (GSU) in patients who underwent radical prostatectomy after extended prostate biopsy in a Chinese population. This retrospective study included a total of 411 patients who underwent radical prostatectomy at our institute after having prostate biopsies between 2011 and 2015. The final pathologic GS was upgraded in 151 (36.74%) of the cases in all patients and 92 (60.13%) cases in men with GS=6. In multivariate analyses, the primary biopsy GS, secondary biopsy GS and obesity were predictive of GSU in the patient cohort assessed. In patients with GS=6, the significant predictors of GSU included the body mass index (BMI), prostate-specific antigen density(PSAD) and percentage of positive cores. The area under the curve (AUC) of the prediction models was 0.753 for the entire patient population and 0.727 for the patients with GS=6. Both nomograms were well calibrated, and decision curve analysis demonstrated a high net benefit across a wide range of threshold probabilities. This study may be relevant for improved risk assessment and clinical decision-making in PCa patients.Entities:
Keywords: Gleason score upgrading; nomogram; prostate biopsy; prostate cancer; prostatectomy
Mesh:
Year: 2016 PMID: 26943768 PMCID: PMC4941387 DOI: 10.18632/oncotarget.7787
Source DB: PubMed Journal: Oncotarget ISSN: 1949-2553
Clinicobiologic and pathologic characteristics of involved patients
| Variable | Overall cohort | GS=6 Cohort |
|---|---|---|
| Age, Mean (SD), yr: | 67.12 (7.24) | 66.06 (7.25) |
| BMI, Mean (SD) | 24.07 (2.78) | 23.84 (2.95) |
| BMI≥24 | 215 (52.31) | 75 (49.02) |
| BMI≥28 | 26 (6.33) | 10 (6.54) |
| PSA, Median (IQR), ng/ml | 10.84 (12.85) | 9.7 (9.16) |
| PV, Median (IQR), ml: | 32.76 (22.23) | 36.4 (27.04) |
| PSAD, Median (IQR), ng/ml per gram | 0.33 (0.44) | 0.29 (0.33) |
| clinical stage | ||
| t1c | 80 (19.46) | 37 (24.18) |
| t2a | 65 (15.82) | 25 (16.34) |
| t2b | 166 (40.39) | 67 (43.79) |
| t2c | 67 (16.30) | 21 (13.73) |
| t3 | 22 (5.35) | 1 (0.65) |
| t4 | 11 (2.68) | 2 (1.31) |
| Biopsy specimens features: | ||
| Biopsy cores, Median (IQR) | 12 (1.00) | 12 (2.00) |
| Postive cores, Median (IQR) | 4 (4.00) | 2 (3.00) |
| % of positive cores, Median (IQR), % | 31 (33.33) | 20 (23.33) |
| Biopsy gleason score, No (%) | ||
| 6 | 153 (37.23) | 153 (100) |
| 3+4 | 84 (20.44) | - |
| 4+3 | 52 (12.65) | - |
| 8 | 70 (17.03) | - |
| 9 | 41 (9.98) | - |
| 10 | 11 (2.68) | - |
| RP specimens features: | ||
| RP Gleason score, No (%) | ||
| 6 | 81 (19.71) | 61 (39.87) |
| 3+4 | 158 (38.44) | 65 (42.48) |
| 4+3 | 60 (14.60) | 17 (11.11) |
| 8 | 51 (12.41) | 6 (3.92) |
| 9 | 55 (13.38) | 4 (2.61) |
| 10 | 6 (1.46) | - |
| PSM, No (%) | 103 (25.06) | 27 (17.65) |
| SVI, No (%) | 48 (11.68) | 4 (2.61) |
| EMI, No (%) | 89 (21.65) | 19 (12.42) |
| LMP, No (%) | 11 (2.68) | - |
| Nerve, No (%) | 117 (28.47) | 25 (16.34) |
PV=prostate volume; PSM=positive surgerical margin; SVI=seminal vesicle invasion; EMI=extraprostic invasion; LMP=lymph node positive;
Paired comparison of biospy and radical prostatectomy Gleason scores in patients with prostate cancer (n=411)
| Biopsy Gleason Score | RP Gleason Score | Total | |||||
|---|---|---|---|---|---|---|---|
| 6 | 3+4 | 4+3 | 8 | 9 | 10 | ||
| 6 | 61 (14.84%) | 65 (15.82%) | 17 (4.14%) | 6 (1.46%) | 4 (0.97%) | - | 153 (37.23%) |
| 3+4 | 10 (2.43%) | 51 (12.41%) | 13 (3.16%) | 6 (1.46%) | 4 (0.97%) | - | 84 (20.44%) |
| 4+3 | 3 (0.73%) | 21 (5.11%) | 9 (2.19%) | 14 (3.41%) | 5 (1.21%) | - | 52 (12.65%) |
| 8 | 4 (0.97%) | 15 (3.65%) | 14 (3.41%) | 21 (5.11%) | 13 (3.16%) | 3 (0.73%) | 70 (17.03%) |
| 9 | 2 (0.49%) | 6 (1.46%) | 6 (1.46%) | 2 (0.49) | 24 (5.84%) | 1 (0.24%) | 41 (9.98%) |
| 10 | 1 (0.24%) | - | 1 (0.24%) | 2 (0.49) | 5 (1.21%) | 2 (0.49) | 11 (2.68%) |
| Total | 81 (19.71%) | 158 (38.44%) | 60 (14.60%) | 51 (12.41%) | 55 (13.38%) | 6 (1.46%) | 411 (100%) |
RP=radical prostatectomy
The results of the univariate logistic regression model of predictors for GSU and GSU from GS=6
| Predictors | Predicting any GSU | AUC | Predicting GSU form GS=6 | AUC | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| OR | 95%CI | P | beta-coefficent | OR | 95%CI | P | beta-coefficent | |||
| Primary GS | 0.66 | - | ||||||||
| 3 | 1.00 (Reference) | |||||||||
| 4 | 0.35 | 0.22-0.02 | <0.001 | −1.06 | ||||||
| 5 | 0.07 | 0.02-0.29 | <0.001 | −2.71 | ||||||
| Secondary GS | 0.70 | - | ||||||||
| 3 | 1.00 (Reference) | |||||||||
| 4 | 0.27 | 0.17-0.42 | <0.001 | −1.31 | ||||||
| 5 | 0 | 0.00-0.00 | 0.997 | −21.34 | ||||||
| non-obesity (BMI<28) | 1.00 (Reference) | |||||||||
| Obesity (BMI>28) | 1.43 | 0.95-2.17 | 0.089 | 0.36 | 0.54 | 2.06 | 0.99-4.28 | 0.052 | 0.72 | 0.58 |
| Age (ys) | 0.51 | 0.53 | ||||||||
| <60 | 1.00 (Reference) | 1.00 (Reference) | ||||||||
| 60-70 | 1.23 | 0.68-2.22 | 0.683 | 0.21 | 1.60 | 0.67-3.80 | 0.287 | 0.47 | ||
| >70 | 1.00 | 0.54-1.86 | 0.991 | −0.64 | 1.43 | 0.56-3.61 | 0.456 | 0.35 | ||
| DRE | 0.91 | 0.58-1.43 | 0.682 | −0.10 | 0.51 | 0.96 | 0.43-2.13 | 0.922 | −0.40 | |
| BMI | 0.99 | 0.97-1.01 | 0.534 | −0.01 | 0.55 | 1.08 | 0.97-1.20 | 0.170 | 0.08 | 0.57 |
| PSA level (ng/ml) | 1.00 | 0.99-1.02 | 0.657 | 1.00 | 0.54 | 1.05 | 1.01-1.09 | 0.013 | 0.05 | 0.65 |
| PSAD | 1.05 | 0.76-1.46 | 0.765 | 0.76 | 0.55 | 11.11 | 2.50-49.38 | 0.002 | 2.41 | 0.67 |
| N of cores taken | 0.75 | 0.36-1.55 | 0.432 | −0.29 | 0.52 | |||||
| <12 | 1.00 (Reference) | 1.00 (Reference) | ||||||||
| ≥12 | 1.31 | 0.84-2.06 | 0.238 | 0.27 | 1.31 | 0.84-2.06 | 0.238 | 0.27 | ||
| N positive cores (n) | 1.02 | 0.96-1.09 | 0.494 | 0.02 | 1.24 | 1.05-1.47 | 0.012 | 0.22 | 0.66 | |
| % positive cores | 1.21 | 0.58-2.53 | 0.606 | 0.19 | 11.38 | 1.63-79.70 | 0.014 | 2.43 | 0.68 | |
| Clinical stage | 0.54 | 0.56 | ||||||||
| T1c | 1.00 (Reference) | 1.00 (Reference) | ||||||||
| T2a | 1.20 | 0.62-2.38 | 0.598 | 0.18 | 2.43 | 0.75-7.96 | 0.141 | 0.89 | ||
| T2b | 0.89 | 0.52-1.55 | 0.692 | −0.11 | 0.71 | 0.31-1.61 | 0.407 | −0.35 | ||
| T2c | 0.83 | 0.42-1.62 | 0.580 | −0.19 | 0.67 | 0.23-1.98 | 0.468 | −0.40 | ||
| T3 | 0.59 | 0.24-1.44 | 0.249 | −0.52 | 1.22 | 0.01-14.70 | 0.877 | 0.20 | ||
| PV (ml) | 0.50 | 0.56 | ||||||||
| <30 | 1.00 (Reference) | 1.00 (Reference) | ||||||||
| 30-45 | 0.65 | 0.40-1.06 | 0.085 | 0.40 | 0.60 | 0.26-1.36 | 0.222 | −0.51 | ||
| >45 | 1.02 | 0.63-1.66 | 0.938 | 0.02 | 0.70 | 0.32-1.52 | 0.361 | −0.36 | ||
| Surgical technique | 0.51 | 0.53 | ||||||||
| ORP | 1.00 (Reference) | 1.00 (Reference) | ||||||||
| LRP | 0.90 | 0.52-1.55 | 0.702 | −0.11 | 0.69 | 0.29-1.64 | 0.401 | −0.37 | ||
| RALP | 1.08 | 0.67-1.76 | 0.750 | 0.08 | 1.07 | 0.50-2.30 | 0.867 | 0.07 | ||
P <0.05 is statistically significant.
The results of the multiple logistic regression model of predictors for GSU and GSU from GS=6
| Predictors | Predicting any GSU | Predictors | Predicting GSU form GS=6 | ||||||
|---|---|---|---|---|---|---|---|---|---|
| OR | 95%CI | P | beta-coefficent | OR | 95%CI | P | beta-coefficent | ||
| Primary GS | Obesity (BMI>28) | 2.02 | 0.93-4.40 | 0.077 | 0.70 | ||||
| 3 | 1.00 (Reference) | ||||||||
| 4 | 0.53 | 0.32-0.87 | 0.012 | −0.64 | |||||
| 5 | 0.14 | 0.03-0.62 | 0.010 | −1.98 | PSAD | 9.66 | 2.16-43.17 | 0.003 | 2.27 |
| Secondary GS | |||||||||
| 3 | 1.00 (Reference) | ||||||||
| 4 | 0.30 | 0.19-0.48 | 0.000 | −1.21 | % positive cores | 10.96 | 1.54-78.09 | 0.017 | 2.39 |
| 5 | 0.00 | 0.00-0.00 | 0.998 | −20.66 | |||||
| Obesity (BMI>28) | 1.72 | 1.08-2.74 | 0.023 | 0.54 | Constant | 0.003 | −1.18 | ||
| AUC | 0.753 (0.706-0.800) | AUC | 0.727 (0.647-0.808) | ||||||
Figure 1Receiver operating characteristic (ROC) curves of the prediction models and single predictors in predicting GSU in
A. all men and B. men with GS=6.
Figure 2Calibration curves of prediction models in
A. the overall patient population and B. the cohort of GSU from GS=6 across all probabilities of GSU.
Figure 3Decision analysis demonstrated ahigh net benefit across a wide range of threshold probabilities in
A. the overall patient population (model 1) and B. the cohort of men with GS=6(model 2). (A): Black: biopsy none; Grey: biopsy all; Dotted black: the primary GSat biopsy; Dotted red: the secondary GSat biopsy; Dotted green: obesity; Dotted Blue: Model 1. (B): Black: biopsy none; Grey: biopsy all; Dotted black: obesity; Dotted red:PSAD;Dotted green: percentage of positive cores; Dotted Blue: Model 2.
Figure 4The nomogram of GSU prediction in
A. the overall patient population and B. the patients with GS=6. Instructions for physicians: To obtain the nomogram-predicted probability of GSU, locate the patient values at each axis. Draw a vertical line to the “Points” axis to determine how many points are attributed for each variable value. Sum the points for all variables. Locate the sum on the “Total Points” line to assess the individual probability of cancer on prostate biopsy on the “Risk” line. Primary GS: the primary GSat biopsy; Secondary GS: the secondary GSat biopsy; PSAD: prostate-specific antigen density; % positive cores: percentage of positive cores.