The primary outcome of patient-reported quality of life is measured by the EORTC QLQ-C30 Physical Function scale. The scale ranges in score from 0 to 100, with higher function scores indicating better health. Scale score is calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100. Each scale requires responses for at least 50% of the items in order to be calculated.

We performed tenfold multiple imputation (MICE R package) for all missing outcomes and covariates for analyses of all patient-reported outcomes.

Patient-reported quality of life is measured by the EORTC QLQ-C30 Physical Function scale. The scale ranges in score from 0 to 100, with higher function scores indicating better health. Scale score is calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100. Each scale requires responses for at least 50% of the items in order to be calculated.

Patient-reported quality of life is measured by the EORTC QLQ-C30 Physical Function scale. The scale ranges in score from 0 to 100, with higher function scores indicating better health. Scale score is calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100. Each scale requires responses for at least 50% of the items in order to be calculated.

The evaluation of the effect of treatment choice on patient-reported urinary health, as measured by the Bladder Cancer Index (BCI). The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score is constructed from the items used to calculate the two subscale scores (function and bother). Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.

We imputed missing outcomes and covariates for TMLE analyses of this outcome. Therefore, all participants who enrolled in CISTO are included whether or not they completed that outcome. The mean and standard deviation for this outcome was calculated using only participants who completed this outcome (n = 292 and 166 for bladder-sparing therapy and radical cystectomy arms, respectively).

The evaluation of the effect of treatment choice on patient-reported urinary health, as measured by the Bladder Cancer Index (BCI). The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score is constructed from the items used to calculate the two subscale scores (function and bother). Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.

The evaluation of the effect of treatment choice on patient-reported urinary health, as measured by the Bladder Cancer Index (BCI). The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score is constructed from the items used to calculate the two subscale scores (function and bother). Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.

The evaluation of the effect of treatment choice on patient-reported sexual health, as measured by the Bladder Cancer Index (BCI). The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score is constructed from the items used to calculate two subscale scores (function and bother). Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.

We imputed missing outcomes and covariates for TMLE analyses of this outcome. Therefore, all participants who enrolled in CISTO are included whether or not they completed that outcome. The mean and standard deviation for this outcome was calculated using only participants who completed this outcome (n = 238 and 143 for bladder-sparing therapy and radical cystectomy arms, respectively).

The evaluation of the effect of treatment choice on patient-reported sexual health, as measured by the Bladder Cancer Index (BCI). The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score is constructed from the items used to calculate two subscale scores (function and bother). Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.

The evaluation of the effect of treatment choice on patient-reported sexual health, as measured by the Bladder Cancer Index (BCI). The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score is constructed from the items used to calculate two subscale scores (function and bother). Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.

The evaluation of the effect of treatment choice on patient-reported bowel health, as measured by the Bladder Cancer Index (BCI). The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score is constructed from the items used to calculate two subscale scores (function and bother). Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.

We imputed missing outcomes and covariates for TMLE analyses of this outcome. Therefore, all participants who enrolled in CISTO are included whether or not they completed that outcome. The mean and standard deviation for this outcome was calculated using only participants who completed this outcome (n = 293 and 166 for bladder-sparing therapy and radical cystectomy arms, respectively).

The evaluation of the effect of treatment choice on patient-reported bowel health, as measured by the Bladder Cancer Index (BCI). The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score is constructed from the items used to calculate two subscale scores (function and bother). Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.

The evaluation of the effect of treatment choice on patient-reported bowel health, as measured by the Bladder Cancer Index (BCI). The BCI consists of 36 items, with 4- or 5-point Likert response scales, covering 3 primary domains: urinary, bowel, and sexual. For each domain a summary score is constructed from the items used to calculate two subscale scores (function and bother). Scores are calculated by transforming item responses into a 0 to 100 scale and calculating the mean of the standardized items. Higher scores indicate better health status. To calculate a score, a minimum of 80% completed items is required.

The evaluation of the effect of treatment choice on patient-reported financial distress, as measured by the Comprehensive Score for Financial Toxicity (COST). The COST questionnaire consists of 11 items, each scored on a 5-point Likert scale from zero to four. After reversing some items as indicated in the scoring manual (by reversing the sign on the original zero to four score and adding four), all item response scores are summed into a single financial toxicity score ranging from 0 to 44, with higher scores indicating greater financial wellbeing. Each subscale requires responses for at least 50% of the items in that subscale in order to be calculated. Item nonresponse is accounted for by substituting the mean of the completed items in the subscale.

We imputed missing outcomes and covariates for TMLE analyses of this outcome. Therefore, all participants who enrolled in CISTO are included whether or not they completed that outcome. The mean and standard deviation for this outcome was calculated using only participants who completed this outcome (n = 288 and 167 for bladder-sparing therapy and radical cystectomy arms, respectively).

The evaluation of the effect of treatment choice on patient-reported financial distress, as measured by the Comprehensive Score for Financial Toxicity (COST). The COST questionnaire consists of 11 items, each scored on a 5-point Likert scale from zero to four. After reversing some items as indicated in the scoring manual (by reversing the sign on the original zero to four score and adding four), all item response scores are summed into a single financial toxicity score ranging from 0 to 44, with higher scores indicating greater financial wellbeing. Each subscale requires responses for at least 50% of the items in that subscale in order to be calculated. Item nonresponse is accounted for by substituting the mean of the completed items in the subscale.

The evaluation of the effect of treatment choice on patient-reported financial distress, as measured by the Comprehensive Score for Financial Toxicity (COST). The COST questionnaire consists of 11 items, each scored on a 5-point Likert scale from zero to four. After reversing some items as indicated in the scoring manual (by reversing the sign on the original zero to four score and adding four), all item response scores are summed into a single financial toxicity score ranging from 0 to 44, with higher scores indicating greater financial wellbeing. Each subscale requires responses for at least 50% of the items in that subscale in order to be calculated. Item nonresponse is accounted for by substituting the mean of the completed items in the subscale.

The evaluation of patient-reported anxiety, as measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Anxiety 4a. Scores range from 0 to 100, with higher scores indicating greater symptoms. Scores are normalized to a mean of 50 and standard deviation of 10.

We imputed missing outcomes and covariates for TMLE analyses of this outcome. Therefore, all participants who enrolled in CISTO are included whether or not they completed that outcome. The mean and standard deviation for this outcome was calculated using only participants who completed this outcome (n = 294 and 169 for bladder-sparing therapy and radical cystectomy arms, respectively).

The evaluation of patient-reported anxiety, as measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Anxiety 4a. Scores range from 0 to 100, with higher scores indicating greater symptoms. Scores are normalized to a mean of 50 and standard deviation of 10.

The evaluation of patient-reported anxiety, as measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Anxiety 4a. Scores range from 0 to 100, with higher scores indicating greater symptoms. Scores are normalized to a mean of 50 and standard deviation of 10.

The evaluation of patient-reported depression, as measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Depression 4a. Scores range from 0 to 100, with higher scores indicating greater symptoms. Scores are normalized to a mean of 50 and standard deviation of 10.

We imputed missing outcomes and covariates for TMLE analyses of this outcome. Therefore, all participants who enrolled in CISTO are included whether or not they completed that outcome. The mean and standard deviation for this outcome was calculated using only participants who completed this outcome (n = 294 and 169 for bladder-sparing therapy and radical cystectomy arms, respectively).

The evaluation of patient-reported depression, as measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Depression 4a. Scores range from 0 to 100, with higher scores indicating greater symptoms. Scores are normalized to a mean of 50 and standard deviation of 10.

The evaluation of patient-reported depression, as measured by the Patient Reported Outcome Measurement Information System (PROMIS) Short Form v1.0 - Depression 4a. Scores range from 0 to 100, with higher scores indicating greater symptoms. Scores are normalized to a mean of 50 and standard deviation of 10.

The evaluation of patient-reported generic quality of life as measured by the EuroQoL EQ-5D-5L (EQ-5D). Scores range from 0 to 1, with higher scores indicating better health.

We imputed missing outcomes and covariates for TMLE analyses of this outcome. Therefore, all participants who enrolled in CISTO are included whether or not they completed that outcome. The mean and standard deviation for this outcome was calculated using only participants who completed this outcome (n = 278 and 162 for bladder-sparing therapy and radical cystectomy arms, respectively).

The evaluation of patient-reported generic quality of life as measured by the EuroQoL EQ-5D-5L (EQ-5D). Scores range from 0 to 1, with higher scores indicating better health.

The evaluation of patient-reported generic quality of life as measured by the EuroQoL EQ-5D-5L (EQ-5D). Scores range from 0 to 1, with higher scores indicating better health.

The evaluation of the effect of treatment choice on recurrence-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (recurrence or death). A recurrence was defined as any subsequent episode of high-grade bladder cancer in the bladder or elsewhere in the urinary tract (penile urethra, prostatic urethra, ureters, renal pelvis), either non-muscle or muscle invasive bladder cancer (for cystectomy arm this excludes any finding at cystectomy). Censoring occurred at the last electronic health record review or death.

All participants who had an electronic health record review or death record at least 12 months after the diagnosis of recurrent high-grade non-muscle invasive bladder cancer. Survival times were calculated from the date of recurrence to the event (metastasis or death). Censoring occurred at the last electronic health record review or death.

The evaluation of the effect of treatment choice on recurrence-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (recurrence or death). A recurrence was defined as any subsequent episode of high-grade bladder cancer in the bladder or elsewhere in the urinary tract (penile urethra, prostatic urethra, ureters, renal pelvis), either non-muscle or muscle invasive bladder cancer (for cystectomy arm this excludes any finding at cystectomy). Censoring occurred at the last electronic health record review or death.

The evaluation of the effect of treatment choice on recurrence-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (recurrence or death). A recurrence was defined as any subsequent episode of high-grade bladder cancer in the bladder or elsewhere in the urinary tract (penile urethra, prostatic urethra, ureters, renal pelvis), either non-muscle or muscle invasive bladder cancer (for cystectomy arm this excludes any finding at cystectomy). Censoring occurred at the last electronic health record review or death.

The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A metastasis was defined as metastasis to distant lymph/nodes organs (pathologic or radiologic diagnosis of M+ disease) (for cystectomy arm this includes findings at cystectomy). Censoring occurred at the last electronic health record review or death.

All participants who had an electronic health record review or death record at least 12 months after the diagnosis of recurrent high-grade non-muscle invasive bladder cancer. Survival times were calculated from the date of recurrence to the event (metastasis or death). Censoring occurred at the last electronic health record review or death.

The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A metastasis was defined as metastasis to distant lymph/nodes organs (pathologic or radiologic diagnosis of M+ disease) (for cystectomy arm this includes findings at cystectomy). Censoring occurred at the last electronic health record review or death.

The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A metastasis was defined as metastasis to distant lymph/nodes organs (pathologic or radiologic diagnosis of M+ disease) (for cystectomy arm this includes findings at cystectomy). Censoring occurred at the last electronic health record review or death.

The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A progression was defined as any subsequent episode of muscle-invasive (T2-T4) disease in the bladder or elsewhere in the urinary tract AND/OR locoregional (true pelvic/common iliac) nodal disease (N+) AND/OR distant metastasis (M+) (for cystectomy arm this includes findings at cystectomy). Censoring occurred at the last electronic health record review or death.

All participants who had an electronic health record review or death record at least 12 months after the diagnosis of recurrent high-grade non-muscle invasive bladder cancer. Survival times were calculated from the date of recurrence to the event (progression or death). Censoring occurred at the last electronic health record review or death.

The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A progression was defined as any subsequent episode of muscle-invasive (T2-T4) disease in the bladder or elsewhere in the urinary tract AND/OR locoregional (true pelvic/common iliac) nodal disease (N+) AND/OR distant metastasis (M+) (for cystectomy arm this includes findings at cystectomy). Censoring occurred at the last electronic health record review or death.

The evaluation of the effect of treatment choice on metastasis-free survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (metastatis or death). A progression was defined as any subsequent episode of muscle-invasive (T2-T4) disease in the bladder or elsewhere in the urinary tract AND/OR locoregional (true pelvic/common iliac) nodal disease (N+) AND/OR distant metastasis (M+) (for cystectomy arm this includes findings at cystectomy). Censoring occurred at the last electronic health record review or death.

The evaluation of the effect of treatment choice on bladder cancer-specific survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death from bladder cancer). Censoring occurred at the last electronic health record review or date of death from bladder cancer.

All participants who had an electronic health record review or death record at least 12 months after the diagnosis of recurrent high-grade non-muscle invasive bladder cancer. Survival times were calculated from the date of recurrence to the event (death from bladder cancer). Censoring occurred at the last electronic health record review or death from bladder cancer.

The evaluation of the effect of treatment choice on bladder cancer-specific survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death from bladder cancer). Censoring occurred at the last electronic health record review or date of death from bladder cancer.

The evaluation of the effect of treatment choice on bladder cancer-specific survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death from bladder cancer). Censoring occurred at the last electronic health record review or date of death from bladder cancer.

The evaluation of the effect of treatment choice on overall survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death). Censoring occurred at the last electronic health record review or date of death.

All participants who had an electronic health record review or submitted a survey at least 12 months after the diagnosis of recurrent high-grade non-muscle invasive bladder cancer or had a death record at any time were included. Participants who did not have an electronic health record review or submit a survey at least 12 months after the diagnosis of recurrent high-grade non-muscle invasive bladder cancer and did not have a death record at any time were excluded.

The evaluation of the effect of treatment choice on overall survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death). Censoring occurred at the last electronic health record review or date of death.

The evaluation of the effect of treatment choice on overall survival. Survival times were calculated from the date of diagnosis of recurrent high-grade non-muscle invasive bladder cancer to the event (death). Censoring occurred at the last electronic health record review or date of death.