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. 2021 Jul 30;11:716741. doi: 10.3389/fonc.2021.716741

Table 3.

Risk predictors of all-cause mortality by the time-to-SPM and site of SPM.

Survival function from the first primary RCC diagnosis Survival function from the SPM diagnosis
Unadjusted sHR (95%CI) P-value Adjusted (s) sHR (95%CI) P-value Unadjusted sHR (95%CI) P-value Adjusted sHR (95%CI) P-value
Time to SPM *§
 >120 months 1 reference 1 reference 1 reference 1 reference
 6<time≤12 months 5.74 (3.87-8.49) <0.001 27.56 (18.27-41.56) <0.001 0.60 (0.40-0.89) 0.011 0.86 (0.57-1.29) 0.470
 12<time≤24 months 5.32 (3.60-7.85) <0.001 25.20 (16.77-37.86) <0.001 0.65 (0.44-0.97) 0.033 0.94 (0.63-1.41) 0.767
 24<time≤36 months 4.89 (3.30-7.24) <0.001 18.65 (12.39-28.06) <0.001 0.72 (0.48-1.08) 0.112 0.99 (0.66-1.49) 0.962
 36<time≤48 months 3.54 (2.38-5.28) <0.001 12.16 (8.04-18.38) <0.001 0.65 (0.44-0.98) 0.040 0.92 (0.61-1.39) 0.696
 48<time≤60 months 3.48 (2.33-5.20) <0.001 9.90 (6.55-14.96) <0.001 0.79 (0.52-1.18) 0.253 1.05 (0.69-1.59) 0.821
 60<time≤72 months 2.96 (1.96-4.45) <0.001 7.34 (4.82-11.16) <0.001 0.82 (0.54-1.24) 0.338 1.05 (0.69-1.60) 0.820
 72<time≤84 months 2.66 (1.76-4.04) <0.001 5.03 (3.28-7.70) <0.001 0.94 (0.61-1.43) 0.757 1.11 (0.73-1.71) 0.625
 84<time≤96 months 2.30 (1.50-3.53) <0.001 3.99 (2.59-6.17) <0.001 0.97 (0.63-1.49) 0.880 1.06 (0.69-1.65) 0.784
 96<time≤108 months 1.78 (1.12-2.84) 0.015 2.81 (1.75-4.52) <0.001 0.97 (0.60-1.55) 0.898 1.18 (0.73-1.90) 0.493
 108<time≤120 months 1.34 (0.80-2.26) 0.269 2.01 (1.18-3.40) 0.010 0.85 (0.50-1.45) 0.559 0.93 (0.54-1.60) 0.786
Types of SPM *#
 Ipsilateral kidney 1 reference 1 reference 1 reference 1 reference
 Contralateral kidney 2.34 (1.23-4.45) 0.009 1.43 (0.74-2.76) 0.286 1.63 (0.86-3.10) 0.133 1.53 (0.79-2.95) 0.206
 Brain 15.68 (7.97-30.85) <0.001 26.36 (12.05-57.65) <0.001 21.06 (10.68-41.52) <0.001 31.40 (14.24-69.23) <0.001
 Cecum/Small Intestine 4.81 (2.40-9.63) <0.001 1.56 (0.76-3.21) 0.223 3.67 (1.83-7.36) <0.001 1.95 (0.95-3.99) 0.068
 Colon/Rectum 5.07 (2.67-9.63) <0.001 2.24 (1.16-4.31) 0.016 3.84 (2.02-7.30) <0.001 2.45 (1.27-4.72) 0.008
 Esophagus/Stomach 10.23 (5.30-19.74) <0.001 3.46 (1.76-6.79) <0.001 9.37 (4.86-18.07) <0.001 3.28 (1.67-6.44) 0.001
 Female Breast 2.12 (1.10-4.07) 0.024 1.51 (0.77-2.98) 0.234 1.64 (0.85-3.16) 0.136 1.54 (0.78-3.03) 0.214
 Gallbladder/bile duct 13.16 (6.53-26.53) <0.001 4.95 (2.40-10.20) <0.001 11.69 (5.80-23.55) <0.001 6.12 (2.97-12.60) <0.001
 Liver 9.30 (4.82-17.95) <0.001 5.18 (2.64-10.17) <0.001 10.01 (5.19-19.32) <0.001 5.94 (3.03-11.66) <0.001
 Lung/Bronchus 9.85 (5.26-18.44) <0.001 3.03 (1.59-5.78) 0.001 8.60 (4.59-16.09) <0.001 3.03 (1.59-5.78) 0.001
 Pancreas 12.11 (6.35-23.09) <0.001 4.46 (2.29-8.68) <0.001 15.06 (7.89-28.72) <0.001 5.85 (3.00-11.42) <0.001
 Prostate 1.74 (0.92-3.29) 0.087 0.43 (0.22-0.83) 0.011 1.21 (0.64-2.28) 0.556 0.49 (0.26-0.95) 0.035
 Thyroid 1.20 (0.57-2.52) 0.635 0.76 (0.36-1.61) 0.468 0.80 (0.38-1.68) 0.552 0.84 (0.40-1.80) 0.658
 Urinary Bladder 3.63 (1.90-6.94) <0.001 3.65 (1.84-7.26) <0.001 2.52 (1.32-4.82) 0.005 3.91 (1.96-7.79) <0.001
 Uteri/Ovary 3.46 (1.73-6.91) <0.001 2.03 (0.99-4.16) 0.053 2.96 (1.48-5.92) 0.002 2.15 (1.05-4.40) 0.036
Types of SPM **
 All site of SPM
 (None-SPM as a reference) ¶
1.40 (1.33-1.46) <0.001 1.26 (1.20-1.32) <0.001
 All site of SPM
 (None-SPM as a reference) θ
1.34 (1.28-1.42) <0.001 1.23 (1.17-1.30) <0.001

SPM, second primary malignancy; CI, confidence interval; sHR, Sub-distribution hazard ratio; AJCC, American Joint Committee on Cancer system; RCC, renal cell carcinoma.

* All SPM in solid malignancy (n= 5008) exclude acute/chronic leukemia/myeloma, melanoma of the skin, NHL/Hodgkin, miscellaneous.

§ Multivariate analysis with all other covariables (age of first primary RCC [for OS from first primary RCC diagnosis analysis] or the age of SPM [for OS from SPM diagnosis analysis], respectively], sex, race, marital status, population, region, family income, tumor grade, histological type of first primary RCC, tumor size of first primary RCC, tumor TNM stage of RCC and SPM, and treatment of RCC and SPM, and types of SPM).

# Multivariate analysis with all other covariables (age of first primary RCC [for OS from first primary RCC diagnosis analysis] or the age of SPM [for OS from SPM diagnosis analysis], respectively], sex, race, marital status, population, region, family income, tumor grade, histological type of first primary RCC, tumor size of first primary RCC, tumor TNM stage of RCC and SPM, and treatment of RCC and SPM, and time-to-SPM).

** Multivariate analysis with all other covariables (age of first primary RCC, sex, race, marital status, population, region, family income, tumor grade, histological type of first primary RCC, tumor TNM stage, and tumor size of first primary RCC) based the data of all cohort including the patient with none-SPM and SPM.

¶ Univariate and multivariate Cox proportional risk regression before propensity score matching.

θ Univariate and multivariate Cox proportional risk regression analysis after 1: 5 propensity score matching.