Associated factors for Gleason grade upgrading after radical prostatectomy and establishment of a predictive Nomogram model
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摘要:目的 分析前列腺穿刺活检Gleason分级≤4级患者根治性前列腺切除术（RP）后Gleason分级升高（GGU）的相关因素，并建立预测GGU的列线图模型。方法 回顾性分析2017年1月—2020年1月河南省人民医院收治的78例穿刺活检Gleason分级≤4级并行RP治疗的患者的临床和病理资料。根据RP后Gleason分级情况分为升高组（n=42）和非升高组（n=36），采用单因素和多因素Logistic回归分析筛选GGU的相关因素，建立预测列线图模型并进行内部验证。结果 本研究中RP后Gleason分级升高42例（53.8%），不变24例（30.8%），下降12例（15.4%）。多因素Logistic回归分析显示，RP前内分泌治疗（OR=3.888，P=0.015）、游离前列腺特异性抗原（FPSA）（OR=1.185，P=0.036）、淋巴细胞（OR=0.271，P=0.027）与GGU相关。以上述因素构建预测列线图模型并进行内部验证，该模型的曲线下面积（AUC）为0.779（95% CI为0.677~0.881），C指数为0.657，平均绝对误差为2.0%。结论 在前列腺穿刺活检Gleason分级≤4级的患者中，RP术前有内分泌治疗史、FPSA越高、淋巴细胞越低者，RP术后GGU的可能性越大。基于上述因素建立的预测列线图模型具有一定的临床应用价值。Abstract:Objective To analyze the related factors for Gleason grade upgrading (GGU) after radical prostatectomy (RP) in patients with Gleason grade ≤ 4 by biopsy, and to establish a predictive Nomogram model.Methods Clinical and pathological materials of 78 patients with Gleason grade ≤ 4 by biopsy and RP therapy in Henan Provincial People's Hospital from January 2017 to January 2020 were analyzed retrospectively. According to the Glason grade after RP, the patients was divided into elevated group (n=42) and non-elevated group (n=36). Univariate and multivariate Logistic regression analyses were used to analyze the associated factors for GGU, and the predictive Nomogram model was established on the basis of internal validation.Results After receiving RP treatment, the Gleason grade were upgraded in 42 cases (53.8%), invariant in 24 cases (30.8%) and downgraded in 12 cases (15.4%). Multivariate Logistic regression analysis showed that the endocrine therapy before RP (OR=3.888, P=0.015), free prostate specific antigen (FPSA) (OR=1.185, P=0.036) and lymphocyte (OR=0.271, P=0.027) were correlated with GGU. Based on the above factors, the predictive Nomogram model was established and verified internally, the area under the curve (AUC) of the model was 0.779 (95%CI, 0.677 to 0.881), the C-index was 0.657, and the average absolute error was 2.0%.Conclusion In patients with Gleason grade ≤ 4 by prostate biopsy, the patients with history of endocrine therapy before RP, increased FPSA and lower lymphocyte are more likely to suffer GGU after RP. The predictive Nomogram model based on the above factors has a certain clinical application value.
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Keywords:
- prostate cancer /
- aspiration biopsy /
- Gleason grade /
- radical prostatectomy /
- Nomogram
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表 1 前列腺穿刺活检和根治性切除术后病理分级变化情况[n(%)]
穿刺活检Gleason分级 RP后病理分级 合计 1级 2级 3级 4级 5级 1级 3(23.08) 2(15.38) 2(15.38) 3(23.08) 3(23.08) 13 2级 1(4.55) 10(45.45) 4(18.18) 2(9.09) 5(22.73) 22 3级 1(6.67) 4(26.67) 2(13.33) 1(6.67) 7(46.67) 15 4级 0 2(7.14) 4(14.29) 9(32.14) 13(46.43) 28 合计 5 18 12 15 28 78 
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表 2 升高组与非升高组临床资料比较(x±s)[M(Q1, Q3)][n(%)]
指标 升高组(n=42) 非升高组(n=36) 年龄/岁 69.07±6.07 69.70±7.84 BMI/(kg/m2) 25.26±2.64 24.67±3.52 TPSA/(ng/mL) 24.03(15.06, 77.31) 14.69(11.56, 29.27)* FPSA/(ng/mL) 2.15(1.49, 8.85) 1.60(0.94, 3.08)** FPSA/TPSA 0.11(0.08, 0.14) 0.10(0.07, 0.14) PSAD 0.80(0.30, 2.06) 0.42(0.21, 0.86)* 白细胞/(×109/L) 5.44(4.74, 6.39) 5.97(5.12, 7.87) 中性粒细胞/(×109/L) 3.22(2.61, 4.56) 3.45(2.88, 4.82) 淋巴细胞/(×109/L) 1.53(1.32, 1.84) 1.85(1.74, 2.14)** 单核细胞/(×109/L) 0.33(0.27, 0.50) 0.36(0.27, 0.52) 血小板/(×109/L) 202.88±41.85 223.97±70.47 NLR 1.98(1.72, 3.24) 1.88(1.52, 2.85) PLR 130.46(100.78, 150.00) 114.88(98.19, 148.33) LMR 4.33(2.82, 6.40) 4.50(3.47, 6.75) 白蛋白/(g/L) 40.77±3.52 41.01±4.25 ALP/(U/L) 66.93±14.86 65.06±14.35 PT/s 12.20±0.74 12.13±0.78 PTA/% 117.00(106.00, 113.00) 120.50(111.50, 132.50) APTT/s 37.10(35.70, 39.40) 35.90(34.00, 39.00) TT/s 16.40(15.70, 17.20) 16.70(16.20, 17.20) 纤维蛋白原/(g/L) 2.94(2.47, 3.52) 3.16(2.57, 3.52) D-二聚体/(g/L) 0.34(0.24, 0.42) 0.33(0.24, 0.53) 血小板分布宽度/fL 12.45(11.00, 13.40) 11.60(10.50, 13.45) 前列腺体积/mL 36.38(23.95, 50.80) 39.60(28.23, 60.31) 穿刺活检至RP间隔时间/d 39.50(31.00, 43.00) 36.00(24.00, 47.50) 阳性针数/针 5.00(3.00, 9.00) 4.00(2.00, 6.00) 高血压病史 有 15(57.69) 11(42.31) 无 27(51.92) 25(48.08) 糖尿病病史 有 7(63.64) 4(36.36) 无 35(52.23) 32(47.76) 家族患癌史 有 8(61.54) 5(38.46) 无 34(52.31) 31(47.69) 吸烟史 有 21(60.00) 14(40.00) 无 21(48.84) 22(51.16) 饮酒史 有 23(57.50) 17(42.50) 无 19(50.00) 19(50.00) RP前内分泌治疗 有 22(75.86) 7(24.14)** 无 20(40.82) 29(59.18)** BMI: 体质量指数; TPSA: 总前列腺特异性抗原; FPSA: 游离前列腺特异性抗原; PSAD: PSA密度; NLR: 中性粒细胞与淋巴细胞比值; PLR: 血小板与淋巴细胞比值; LMR: 淋巴细胞与单核细胞比值; ALP: 碱性磷酸酶; PT: 凝血酶原时间; PTA: 凝血酶原活动度; APTT: 活化部分凝血酶原时间; TT: 凝血酶时间; RP: 根治性前列腺切除术。与升高组比较, * P＜0.05, * * P＜0.01。
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表 3 升高组与非升高组病理资料比较[n(%)]
指标 升高组(n=42) 非升高组(n=36) 穿刺主要评分 ≤3分 22(55.00) 18(45.00) >3分 20(52.63) 18(47.37) 穿刺次要评分 ≤3分 19(73.08) 7(26.92)* >3分 23(44.23) 29(55.77)* 穿刺总评分 ≤6分 10(76.92) 3(23.08) 7分 19(51.35) 18(48.65) 8分 13(46.43) 15(53.57) 穿刺Gleason分级 1级 10(76.92) 3(23.08) 2级 11(50.00) 11(50.00) 3级 8(53.33) 7(46.67) 4级 13(46.43) 15(53.57) 淋巴结转移 有 5(11.90) 1(2.78) 无 37(88.10) 35(97.22) 精囊侵犯 是 12(28.57) 5(13.89) 否 30(71.43) 31(86.11) 输精管侵犯 是 9(21.43) 0** 否 33(78.57) 36(100.00)** 神经侵犯 是 34(80.95) 20(55.56)* 否 8(19.05) 16(44.44)* 切缘阳性 是 24(57.14) 8(22.22)** 否 18(42.86) 28(77.78)** 与升高组比较, * P＜0.05, * * P＜0.01。
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表 4 影响GGU的单因素Logistic回归分析
指标 P OR 95%CI 年龄 0.690 0.987 0.925~1.053 BMI 0.396 1.066 0.920~1.236 TPSA 0.131 1.007 0.998~1.016 FPSA 0.016 1.206 1.035~1.406 FPSA/TPSA 0.849 0.516 0.001~474.361 PSAD 0.078 1.384 0.964~1.988 白细胞 0.368 0.418 0.063~2.778 中性粒细胞 0.512 2.532 0.157~40.811 淋巴细胞 0.018 0.284 0.100~0.805 单核细胞 0.995 1.008 0.113~8.990 血小板 0.111 0.993 0.985~1.002 NLR 0.439 1.174 0.782~1.763 PLR 0.269 1.006 0.995~1.017 LMR 0.212 0.887 0.734~1.071 白蛋白 0.776 0.983 0.875~1.105 碱性磷酸酶 0.570 1.009 0.978~1.041 PT 0.662 1.141 0.631~2.065 PTA 0.458 0.993 0.974~1.012 ATPP 0.552 1.040 0.915~1.181 TT 0.167 0.761 0.517~1.121 纤维蛋白原 0.898 0.970 0.610~1.543 D-二聚体 0.205 0.235 0.025~2.208 血小板分布宽度 0.256 1.109 0.928~1.325 前列腺体积 0.706 0.996 0.974~1.018 穿刺活检至RP间隔时间 0.640 1.005 0.985~1.024 阳性针数 0.092 1.132 0.980~1.307 高血压病史 0.630 1.263 0.489~3.263 糖尿病病史 0.485 1.600 0.428~5.982 家族患癌史 0.544 1.459 0.431~4.935 吸烟史 0.326 1.571 0.670~3.876 饮酒史 0.507 1.353 0.554~3.304 RP前内分泌治疗 0.004 4.557 1.637~12.684 穿刺主要评分 0.834 0.909 0.373~2.216 穿刺次要评分 0.019 0.292 0.105~0.814 穿刺总评分 0.075 0.569 0.306~1.058 穿刺Gleason分级 0.144 0.736 0.489~1.110 淋巴结转移 0.166 4.730 0.526~42.524 精囊侵犯 0.124 2.480 0.779~7.893 神经侵犯 0.018 3.400 1.235~9.359 切缘阳性 0.002 4.667 1.725~12.627 BMI: 体质量指数; TPSA: 总前列腺特异性抗原; FPSA: 游离前列腺特异性抗原; PSAD: PSA密度; NLR: 中性粒细胞与淋巴细胞比值; PLR: 血小板与淋巴细胞比值; LMR: 淋巴细胞与单核细胞比值; ALP: 碱性磷酸酶; PT: 凝血酶原时间; PTA: 凝血酶原活动度; APTT: 活化部分凝血酶原时间; TT: 凝血酶时间; RP: 根治性前列腺切除术。
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