Supplementary Table 3 – Univariatelinear regression analysis for disease specific survival for all patients

Covariate / N / Event / Median DSS (95%CI) / Rate at 5 Years (95%CI) / Rate at 10 Years (95%CI) / P-value
324 / 70
Treatment / Upfront RC / 205 / 80 / NA ( 188.86 , NA ) / 0.822 ( 0.778 , 0.869 ) / 0.734 ( 0.673 , 0.801 ) / 0.549
Primary BCG with Delayed RC / 131 / 44 / NA ( NA , NA ) / 0.791 ( 0.73 , 0.857 ) / 0.699 ( 0.608 , 0.804 )
Gender / Male / 284 / 105 / 188.86 ( 130.22 , NA ) / 0.867 ( 0.806 , 0.932 ) / 0.776 ( 0.695 , 0.867 ) / 0.822
Female / 52 / 19 / NA ( 140.8 , NA ) / 0.826 ( 0.778 , 0.877 ) / 0.728 ( 0.661 , 0.802 )
Ethnicity / White / 295 / 110 / 188.86 ( 122.93 , NA ) / 0.806 ( 0.694 , 0.937 ) / 0.773 ( 0.651 , 0.918 ) / 0.012
Black / 13 / 6 / NA ( 188.86 , NA ) / 0.818 ( 0.77 , 0.869 ) / 0.743 ( 0.681 , 0.812 )
Hispanic / 27 / 7 / 79.53 ( 67.41 , NA ) / 0.821 ( 0.621 , 1 )
Asian / 1 / 1 / NA ( 140.8 , NA ) / 0.913 ( 0.805 , 1 ) / 0.913 ( 0.805 , 1 )
Smoking Status / Never / 109 / 42 / 30.22 ( NA , NA ) / 0.174
Active / 61 / 28 / NA ( 122.93 , NA ) / 0.761 ( 0.673 , 0.861 ) / 0.626 ( 0.511 , 0.768 )
Former / 161 / 53 / 188.86 ( NA , NA ) / 0.816 ( 0.713 , 0.933 ) / 0.74 ( 0.609 , 0.9 )
Unknown / 1 / 1 / NA ( NA , NA ) / 0.856 ( 0.798 , 0.917 ) / 0.793 ( 0.72 , 0.874 )
ASA Status / 1 / 4 / 2 / 137.19 ( NA , NA ) / 1 ( 1 , 1 ) / 1 ( 1 , 1 ) / 0.305
2 / 39 / 5 / NA ( 30.22 , NA ) / 0.667 ( 0.3 , 1 )
3 / 231 / 84 / NA ( NA , NA ) / 0.892 ( 0.797 , 0.998 ) / 0.842 ( 0.719 , 0.987 )
4 / 24 / 15 / NA ( 140.8 , NA ) / 0.819 ( 0.764 , 0.878 ) / 0.757 ( 0.69 , 0.83 )
ECOG Performance Status / 0 / 326 / 118 / NA ( 122.24 , NA ) / 0.758 ( 0.594 , 0.968 ) / 0.758 ( 0.594 , 0.968 ) / 0.003
1 / 9 / 5 / NA ( 188.86 , NA ) / 0.833 ( 0.789 , 0.879 ) / 0.743 ( 0.682 , 0.81 )
2 / 1 / 1 / 49.74 ( 24.97 , NA ) / 0.257 ( 0.052 , 1 )
BMI / <30 / 185 / 67 / NA ( NA , NA ) / 0.467
30 / 100 / 36 / NA ( 140.8 , NA ) / 0.804 ( 0.743 , 0.871 ) / 0.748 ( 0.674 , 0.829 )
TURBT Adenocarcinoma / Absent / 334 / 124 / NA ( 137.19 , NA ) / 0.855 ( 0.781 , 0.935 ) / 0.799 ( 0.71 , 0.9 ) / 0.401
Present / 2 / 0 / 188.86 ( 140.8 , NA ) / 0.821 ( 0.776 , 0.868 ) / 0.732 ( 0.671 , 0.799 )
TURBT -Glandular features / Absent / 313 / 116 / NA ( NA , NA ) / 1 ( 1 , 1 ) / 1 ( 1 , 1 ) / 0.661
Present / 23 / 8 / 188.86 ( 140.8 , NA ) / 0.825 ( 0.78 , 0.874 ) / 0.731 ( 0.667 , 0.801 )
TURBT - Micropapillary / Absent / 304 / 114 / NA ( NA , NA ) / 0.779 ( 0.607 , 0.999 ) / 0.779 ( 0.607 , 0.999 ) / 0.361
Present / 32 / 10 / NA ( 188.86 , NA ) / 0.808 ( 0.76 , 0.859 ) / 0.742 ( 0.683 , 0.805 )
TURBT -Nested Variant / Absent / 335 / 123 / NA ( 119.25 , NA ) / 0.966 ( 0.901 , 1 ) / 0.543 ( 0.235 , 1 ) / 0.273
Present / 1 / 1 / NA ( 188.86 , NA ) / 0.822 ( 0.777 , 0.869 ) / 0.733 ( 0.672 , 0.8 )
TURBT - Sarcomatoid / Absent / 327 / 118 / 122.93 ( NA , NA ) / 1 ( 1 , 1 ) / 1 ( 1 , 1 ) / < 0.0001
Present / 9 / 6 / NA ( 188.86 , NA ) / 0.838 ( 0.794 , 0.884 ) / 0.748 ( 0.687 , 0.815 )
TURBT -Signet ring / Absent / 334 / 122 / 30.22 ( 9.79 , NA ) / 0.333 ( 0.132 , 0.84 ) / 0.682
Present / 2 / 2 / NA ( 140.8 , NA ) / 0.822 ( 0.777 , 0.869 ) / 0.733 ( 0.672 , 0.8 )
TURBT - Lymphoepithelioma / Absent / 334 / 123 / 188.86 ( NA , NA ) / 1 ( 1 , 1 ) / 1 ( 1 , 1 ) / 0.36
Present / 2 / 1 / 188.86 ( 140.8 , NA ) / 0.821 ( 0.776 , 0.869 ) / 0.733 ( 0.671 , 0.799 )
TURBT- Squamous / Absent / 311 / 113 / NA ( NA , NA ) / 1 ( 1 , 1 ) / 1 ( 1 , 1 ) / 0.357
Present / 25 / 11 / 188.86 ( 140.8 , NA ) / 0.831 ( 0.786 , 0.879 ) / 0.736 ( 0.672 , 0.805 )
TURBT - Plasmacytoid / Absent / 334 / 122 / NA ( NA , NA ) / 0.699 ( 0.521 , 0.938 ) / 0.699 ( 0.521 , 0.938 ) / < 0.0001
Present / 2 / 2 / NA ( 188.86 , NA ) / 0.828 ( 0.784 , 0.874 ) / 0.739 ( 0.678 , 0.806 )
TURBT -Clear Cell / Absent / 335 / 124 / 15.13 ( 7.29 , NA ) / 0.699
Present / 1 / 0 / 188.86 ( 188.86 , NA ) / 0.822 ( 0.777 , 0.869 ) / 0.734 ( 0.673 , 0.8 )
Any intravesicalTx / Absent / 157 / 56 / NA ( NA , NA ) / 0.769
Present / 179 / 68 / NA ( NA , NA ) / 0.775 ( 0.704 , 0.853 ) / 0.75 ( 0.674 , 0.834 )
BCG with IFN / None / 315 / 116 / 188.86 ( 130.22 , NA ) / 0.861 ( 0.807 , 0.918 ) / 0.735 ( 0.654 , 0.827 ) / 0.599
Given / 19 / 7 / 188.86 ( 140.8 , NA ) / 0.825 ( 0.779 , 0.873 ) / 0.727 ( 0.662 , 0.798 )
Unknown / 1 / 0 / NA ( NA , NA ) / 0.83 ( 0.671 , 1 ) / 0.83 ( 0.671 , 1 )
Number of Induction BCG Courses / 0 / 163 / 59 / NA ( NA , NA ) / 1 ( 1 , 1 ) / 0.376
1 / 138 / 48 / NA ( NA , NA ) / 0.779 ( 0.71 , 0.855 ) / 0.755 ( 0.681 , 0.836 )
2 / 35 / 17 / 188.86 ( 128.32 , NA ) / 0.865 ( 0.802 , 0.932 ) / 0.782 ( 0.701 , 0.873 )
Received optimal BCG maintenance / No / 267 / 97 / 130.22 ( 119.25 , NA ) / 0.843 ( 0.725 , 0.98 ) / 0.581 ( 0.396 , 0.853 ) / 0.633
Yes / 67 / 26 / NA ( NA , NA ) / 0.817 ( 0.767 , 0.871 ) / 0.738 ( 0.674 , 0.808 )
Unknown / 2 / 1 / 137.19 ( 128.32 , NA ) / 0.838 ( 0.746 , 0.942 ) / 0.753 ( 0.615 , 0.922 )
Response / Responsive / 0 / 0 / 90.54 ( NA , NA ) / 1 ( 1 , 1 ) / < 0.0001
Refractory / 99 / 30 / 4.99 ( NA , NA )
Early Relapse / 52 / 25 / NA ( 188.86 , NA ) / 0.865 ( 0.793 , 0.943 ) / 0.734 ( 0.613 , 0.88 )
Intolerant / 11 / 3 / 130.22 ( 122.24 , NA ) / 0.878 ( 0.782 , 0.985 ) / 0.732 ( 0.591 , 0.906 )
Unknown / 2 / 2 / NA ( 126.81 , NA ) / 0.909 ( 0.754 , 1 ) / 0.758 ( 0.506 , 1 )
Late Relapse / 12 / 6
Progressed to T1HG on or post BCG / No / 284 / 102 / 128.32 ( 73.03 , NA ) / 0.733 ( 0.515 , 1 ) / 0.642 ( 0.413 , 0.996 ) / 0.369
Yes / 51 / 22 / NA ( 188.86 , NA ) / 0.825 ( 0.777 , 0.876 ) / 0.755 ( 0.695 , 0.819 )
Reresection / No / 83 / 31 / NA ( 119.25 , NA ) / 0.805 ( 0.69 , 0.938 ) / 0.528 ( 0.285 , 0.977 ) / 0
Yes / 252 / 92 / NA ( 128.32 , NA ) / 0.882 ( 0.809 , 0.963 ) / 0.783 ( 0.682 , 0.898 )
Unknown / 1 / 1 / 188.86 ( 140.8 , NA ) / 0.807 ( 0.754 , 0.863 ) / 0.726 ( 0.655 , 0.805 )
Disease at re-resection / No / 46 / 11 / 16.1 ( NA , NA ) / 0
Yes / 205 / 80 / NA ( 122.24 , NA ) / 0.881 ( 0.788 , 0.985 ) / 0.881 ( 0.788 , 0.985 )
Persistent T1HG at re-resection / No / 95 / 29 / 188.86 ( 140.8 , NA ) / 0.797 ( 0.737 , 0.861 ) / 0.707 ( 0.628 , 0.795 ) / < 0.0001
Yes / 156 / 62 / 188.86 ( 137.19 , NA ) / 0.899 ( 0.834 , 0.969 ) / 0.838 ( 0.74 , 0.948 )
Tumor at dome / No / 288 / 108 / NA ( 140.8 , NA ) / 0.757 ( 0.686 , 0.837 ) / 0.662 ( 0.566 , 0.774 ) / 0.775
Yes / 45 / 15 / NA ( 140.8 , NA ) / 0.829 ( 0.782 , 0.878 ) / 0.756 ( 0.696 , 0.821 )
Tumor at Trigone or Bladder Neck / No / 215 / 74 / NA ( 119.25 , NA ) / 0.797 ( 0.672 , 0.945 ) / 0.594 ( 0.388 , 0.91 ) / 0.247
Yes / 119 / 49 / NA ( NA , NA ) / 0.836 ( 0.782 , 0.893 ) / 0.758 ( 0.683 , 0.841 )
Extensive invasion beyond lamina propria / No / 229 / 85 / 188.86 ( 126.81 , NA ) / 0.803 ( 0.727 , 0.888 ) / 0.698 ( 0.599 , 0.813 ) / 0.013
Yes / 105 / 38 / NA ( NA , NA ) / 0.855 ( 0.806 , 0.908 ) / 0.773 ( 0.708 , 0.843 )
Muscularis Mucosa Involvement / No / 270 / 99 / 122.93 ( 119.25 , NA ) / 0.753 ( 0.665 , 0.854 ) / 0.627 ( 0.481 , 0.817 ) / 0.427
Yes / 64 / 24 / NA ( 140.8 , NA ) / 0.835 ( 0.786 , 0.886 ) / 0.741 ( 0.673 , 0.816 )
Multifocal tumor / No / 117 / 43 / 188.86 ( 122.24 , NA ) / 0.784 ( 0.682 , 0.901 ) / 0.714 ( 0.591 , 0.864 ) / 0.899
Yes / 219 / 81 / NA ( 128.32 , NA ) / 0.81 ( 0.731 , 0.897 ) / 0.754 ( 0.662 , 0.86 )
Architecture / No / 272 / 101 / NA ( 188.86 , NA ) / 0.828 ( 0.775 , 0.885 ) / 0.723 ( 0.645 , 0.81 ) / 0.86
Yes / 63 / 23 / 188.86 ( 140.8 , NA ) / 0.83 ( 0.781 , 0.881 ) / 0.724 ( 0.652 , 0.803 )
LVI at TURBT / No / 298 / 112 / NA ( NA , NA ) / 0.786 ( 0.68 , 0.908 ) / 0.758 ( 0.646 , 0.89 ) / 0.707
Yes / 38 / 12 / 188.86 ( 140.8 , NA ) / 0.821 ( 0.774 , 0.871 ) / 0.731 ( 0.667 , 0.802 )
CIS at TURBT / No / 177 / 61 / NA ( NA , NA ) / 0.832 ( 0.705 , 0.982 ) / 0.773 ( 0.62 , 0.963 ) / 0.656
Yes / 159 / 63 / NA ( 128.32 , NA ) / 0.787 ( 0.72 , 0.861 ) / 0.741 ( 0.654 , 0.839 )
Abnormal EUA / No / 307 / 112 / 188.86 ( 188.86 , NA ) / 0.857 ( 0.8 , 0.917 ) / 0.732 ( 0.651 , 0.823 ) / 0.966
Yes / 29 / 12 / 188.86 ( 140.8 , NA ) / 0.827 ( 0.782 , 0.876 ) / 0.733 ( 0.67 , 0.803 )
Pre-Op Hydro / No / 299 / 107 / NA ( NA , NA ) / 0.764 ( 0.599 , 0.973 ) / 0.764 ( 0.599 , 0.973 ) / 0.11
Yes / 35 / 16 / NA ( 188.86 , NA ) / 0.836 ( 0.79 , 0.884 ) / 0.748 ( 0.685 , 0.817 )
Unknown / 2 / 1 / 126.81 ( 91.82 , NA ) / 0.736 ( 0.59 , 0.916 ) / 0.613 ( 0.403 , 0.933 )
Muscle in Specimen / No / 32 / 10 / 84.63 ( 55.91 , NA ) / 0.5 ( 0.125 , 1 ) / 0.745
Yes / 304 / 114 / NA ( NA , NA ) / 0.721 ( 0.563 , 0.924 ) / 0.721 ( 0.563 , 0.924 )
Prostatic Duct Involvement / No / 306 / 112 / 188.86 ( 140.8 , NA ) / 0.832 ( 0.787 , 0.881 ) / 0.736 ( 0.671 , 0.806 ) / 0.163
Yes / 29 / 12 / NA ( 188.86 , NA ) / 0.833 ( 0.788 , 0.881 ) / 0.738 ( 0.675 , 0.808 )
Size on Endoscopy / <1cm / 8 / 0 / 130.22 ( 130.22 , NA ) / 0.685 ( 0.509 , 0.92 ) / 0.685 ( 0.509 , 0.92 ) / 0.032
1-4cm / 99 / 36 / NA ( 128.32 , NA ) / 1 ( 1 , 1 ) / 1 ( 1 , 1 )
>4cm / 136 / 54 / NA ( 140.8 , NA ) / 0.904 ( 0.842 , 0.97 ) / 0.787 ( 0.687 , 0.902 )
unknown / 56 / 22 / NA ( NA , NA ) / 0.801 ( 0.731 , 0.878 ) / 0.689 ( 0.593 , 0.799 )
Number of resections / 2 or less / 139 / 48 / 122.24 ( 122.24 , NA ) / 0.664 ( 0.526 , 0.84 ) / 0.664 ( 0.526 , 0.84 ) / 0.463
> 2 / 197 / 76 / NA ( NA , NA ) / 0.794 ( 0.721 , 0.875 ) / 0.695 ( 0.596 , 0.81 )
Complete resection / No / 39 / 17 / 188.86 ( 140.8 , NA ) / 0.841 ( 0.786 , 0.899 ) / 0.759 ( 0.686 , 0.84 ) / 0.738
Yes / 287 / 105 / NA ( NA , NA ) / 0.767 ( 0.625 , 0.942 ) / 0.767 ( 0.625 , 0.942 )
Tumor in Diverticulum / No / 305 / 115 / 188.86 ( 140.8 , NA ) / 0.827 ( 0.78 , 0.877 ) / 0.735 ( 0.671 , 0.806 ) / 0.833
Yes / 25 / 8 / NA ( 128.32 , NA ) / 0.857 ( 0.633 , 1 ) / 0.857 ( 0.633 , 1 )
NAC / No / 310 / 118 / NA ( 188.86 , NA ) / 0.821 ( 0.775 , 0.869 ) / 0.729 ( 0.667 , 0.798 ) / 0.726
Yes / 26 / 6 / 188.86 ( 188.86 , NA ) / 0.824 ( 0.777 , 0.873 ) / 0.729 ( 0.665 , 0.799 )
Number of Variant Histologies / 0 / 254 / 91 / NA ( 140.8 , NA ) / 0.816 ( 0.667 , 0.999 ) / 0.816 ( 0.667 , 0.999 ) / 0.132
1 / 69 / 27 / 188.86 ( 140.8 , NA ) / 0.816 ( 0.769 , 0.865 ) / 0.721 ( 0.657 , 0.792 )
2 / 11 / 4 / NA ( NA , NA ) / 0.911 ( 0.8 , 1 ) / 0.911 ( 0.8 , 1 )
3 / 2 / 2 / NA ( 188.86 , NA ) / 0.822 ( 0.778 , 0.869 ) / 0.734 ( 0.673 , 0.801 )
Any Variant Histology present / No / 254 / 91 / < 0.0001
Yes / 82 / 33 / NA ( 140.8 , NA ) / 0.826 ( 0.775 , 0.88 ) / 0.746 ( 0.682 , 0.817 )
Number of HRF / 0 / 159 / 57 / 188.86 ( 122.93 , NA ) / 0.858 ( 0.77 , 0.955 ) / 0.713 ( 0.551 , 0.923 ) / 0.021
1 / 140 / 48 / NA ( 16.1 , NA ) / 0.583 ( 0.34 , 1 ) / 0.583 ( 0.34 , 1 )
2 / 32 / 18 / 7.29 ( NA , NA )
3 / 4 / 1 / NA ( 140.8 , NA ) / 0.826 ( 0.775 , 0.88 ) / 0.746 ( 0.682 , 0.817 )
Number of HRF / 0 / 159 / 57 / 188.86 ( 122.93 , NA ) / 0.808 ( 0.719 , 0.909 ) / 0.685 ( 0.538 , 0.873 ) / 0.011
1 / 140 / 48 / NA ( 140.8 , NA ) / 0.836 ( 0.775 , 0.902 ) / 0.749 ( 0.671 , 0.835 )
2 / 36 / 19 / 188.86 ( 130.22 , NA ) / 0.865 ( 0.803 , 0.932 ) / 0.755 ( 0.649 , 0.878 )

ASA – American society of Anesthesiology classification, BMI – Body mass index, ECOG – eastern cooperative group performance status, BCG – BacillisCalmette-Guerin, IFN- Interferon, TURBT – transurethral resection of bladder tumor, LVI – Lymphovascular invasion, cis – Carcinoma in situ, EUA – exam under anesthesia, NAC- neoadjuvant chemotherapy, HRF – High Risk Features. High risk features are defined as the presence of lymphovascular invasion, variant histology (excluding neuroendocrine), and presence of tumor associated hydronephrosis and thickening or induration felt on exam under anesthesia.*Extensive involvement beyond lamina propria is a subjective outcome referring to any pathologist comment referring to significant depth of penetration beyond lamina propria. Most common terms used to describe this include extensive, significant, deep involvement or approaching but not touching muscularispropria.