Porena 2010.

Study characteristics
Methods	Study design: randomized controlled trial Setting/country: single center in Italy Dates when study was conducted: January 2004 to December 2006
Participants	Ethnicity: NA Inclusion criteria Ages 18–75 years Primary diagnosis of high‐risk superficial bladder cancer according to EAU guidelines Participants having never been treated with other intravesical chemotherapeutic agents, and consenting to participate in the study Exclusion criteria Concomitant tumors Urinary tract infections Altered function of the liver, kidneys, bone marrow, or a combination of these; major cardiovascular diseases Life expectancy < 1 year Intravesical chemotherapy in the previous 3 months or immunotherapy in the previous 6 months Systemic chemotherapy and pelvic radiation therapy prior to TURBT, and any condition that, in the judgment of the investigators, would interfere with the person's ability to provide informed consent, comply with study instructions, place the person at increased risk, or which might confound interpretation of study results Total number of participants randomly assigned Screened: 74 Eligible: 64 Disease type: primary high‐risk disease Intervention: gemcitabine Number of all participants randomly assigned: 32 Age: mean 70.2 (SD 5.5) years Gender (men/women): 26/6 Tumor T stage and grade Ta‐T1 G3: 26; T1 G3 or CIS or G3 + CIS: 6 Tumor size (< 3 cm/≥ 3 cm): NA Number of tumors (1/> 1): NA Comparator: BCG Number of all participants randomly assigned: 32 Age: mean 68.7 (SD 10.2) years Gender (men/women): 28/4 Tumor T stage and grade Ta‐T1 G3: 28; T1 G3 or CIS or G3 + CIS: 4 Tumor size (< 3 cm/≥ 3 cm): NA Number of tumors (1/> 1): NA
Interventions	Intervention: gemcitabine Gemcitabine 2000 mg/50 mL saline 14 days after the second‐look TUR, 6 weekly instillations of gemcitabine held in bladder for 2 hours as induction therapy. If there was no recurrence, participants received maintenance therapy 3, 6, 12, 18, 24, 30, and 36 months Comparator: BCG BCG (Tice strain) 5 × 108 CFU/50 mL saline 14 days after the second‐look TUR, 6 weekly instillations of BCG held in bladder for 2 hours as induction therapy. If there was no recurrence, participants received maintenance therapy 3, 6, 12, 18, 24, 30, and 36 months Follow‐up: mean 44 months
Outcomes	Primary outcomes Recurrence and progression rates; intervals before recurrence and progression How measured: cytology, cystoscopy, and cold‐cup biopsy of any suspicious lesions Time point measured: every 3 months for the first 2 years, every 6 months for the following 3 years, and then annually Time point reported: NA Secondary outcomes Tolerability (dropped out of the study, and safety) How measured: recording of adverse events Time point measured: NA Time point reported: likely cumulative Subgroup analysis: none
Funding Sources	NA
Declarations of interest	NA
Notes	Protocol: NCT00696579 Language of publication: English
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from publication: "the randomisation code was developed using a computer random number generator to select random permuted blocks." Comment: we considered this method of random sequence generation to have low risk of bias.
Allocation concealment (selection bias)	Unclear risk	Comment: no information given.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote from publication: "All study personnel and participants were not blinded to treatment assignment."
Blinding of outcome assessment (detection bias) Subjective outcomes	High risk	Quote from publication: "All study personnel and participants were not blinded to treatment assignment."
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Comment: objective outcomes not likely affected by lack of blinding.
Incomplete outcome data (attrition bias) Time to recurrence	Low risk	Comment: no loss to follow‐up; all randomized participants were included in the analysis.
Incomplete outcome data (attrition bias) Time to progression	Low risk	Comment: no loss to follow‐up; all randomized participants were included in the analysis (no progression in both arms).
Incomplete outcome data (attrition bias) Grade III–V adverse events	Low risk	Comment: all randomized participants were included in the analysis, but no explicit description of grade III–V complications.
Incomplete outcome data (attrition bias) Grade I or II adverse events	Low risk	Comment: all randomized participants were included in the analysis, but no explicit description of grade I or II complications.
Selective reporting (reporting bias)	Low risk	Comment: the protocol (NCT00696579) and all predefined outcomes were provided.
Other bias	Low risk	Comment: not detected.

BCG: Bacillus Calmette‐Guérin; CFU: colony‐forming units; CIS: carcinoma in situ; EAU: European Association of Urology; EORTC QLQ‐C30: European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30; EORTC QLQ‐BLS 24: European Organization for the Research and Treatment of Cancer Quality of Life Superficial Bladder Cancer‐Specific 24; G: tumor grade; HR: hazard ratio; IQR: interquartile range; NMIBC: non‐muscle invasive bladder cancer; NA: not available; SD: standard deviation; TCC: transitional cell carcinoma; TUR: transurethral resection; TURBT: transurethral resection of the bladder tumor; WHO: World Health Organization.