HYMN: a trial comparing hyperthermia and mitomycin chemotherapy with a second BCG treatment, or other standard treatment, for bladder cancer that has come back

Current primary outcome measures as of 11/02/2013:
1. Disease-free survival. For patients without CIS at baseline and those with CIS at baseline but not at the 3-month surveillance visit, this is defined as the interval in whole days between the date of randomisation into the trial and the earliest of date of detection of recurrent disease, or date of death from any cause. For patients with CIS at baseline and at the 3-month surveillance visit, this is defined as the interval in whole days between the date of randomisation and the date of their 3-month surveillance visit. Disease recurrence is defined as the presence of urothelial cell carcinoma or positive cytology. Disease progression is defined as T2 disease or evidence extravesical disease. For those patients who do not have recurrent disease or die during the course of the trial, disease-free survival times will be censored at the last follow-up date. Patients who experience a distant upper-tract recurrence will be censored at the last available assessment. Disease-free survival will be followed-up for 2 years from the first treatment.
2. Complete-response rate at 3 months. For patients with CIS at randomisation, complete response at 3 months is defined as absence of visible tumour recurrence at cystoscopy, negative cytology and no evidence of CIS on random (4 quadrant) biopsy of the bladder.

Previous primary outcome measures until 11/02/2013:
1. Disease-free survival. Defined as the interval in whole days between the date of randomisation into the trial and the earliest of date of detection of recurrent disease, or date of death from any cause. This will also include the interval in whole days between the date proved tumour free (by cystoscopy, negative cytology and biopsy) and the earliest of date of detection of recurrent disease, or date of death from any cause in patients with CIS at randomisation. Disease recurrence is defined as the presence of urothelial cell carcinoma or positive cytology. Disease progression is defined as T2 disease or evidence extravesical disease. For those patients who do not have recurrent disease or die during the course of the trial, disease-free survival times will be censored at the last follow-up date. Patients who experience a distant upper-tract recurrence will be censored at the last available assessment. Disease-free survival will be followed-up for 2 years from the first treatment.
2. Complete-response rate at 3 months. For patients with CIS, complete response at 3 months is defined as absence of visible tumour recurrence at cystoscopy, negative cytology and no evidence of CIS on random (4 quadrant) biopsy of the bladder.

1. Progression-free survival. Defined as the interval in whole days between the date of randomisation into the trial and the earliest of date of detection of disease progression, or date of death from any cause. Disease progression is defined as stage T2 disease or greater confirmed by histopathology following TUR (>=pT2). For those patients who do not experience disease progression or die during the course of the trial, progression-free survival times will be censored at the last follow-up date. Patients who experience a distant upper-tract recurrence will be censored at the last available assessment.
2. Overall survival. Defined as the interval in whole days between the date of randomisation into the trial and date of death from any cause; patients who do not die during the course of the trial will be censored at the last follow-up date.
3. Disease-specific survival. Defined as the interval in whole days between the date of randomisation into the trial and date of death due to bladder cancer. Patients who do not die during the course of the trial will be censored at the last follow-up date. Patients who die of other causes will be censored at date of death due to other cause.
4. Recurrence-free survival. Recurrence-free survival will be measured in patients with papillary disease only. It is defined in the same way as disease-free survival, with the important distinction that CIS at the first three-month post-treatment visit will not be included as an event, but rather considered a treatment failure and will be censored. Patients who entered with CIS, became negative at first control, will be also followed up for recurrence free from first control.
5. Safety and tolerability of HM. Safety and tolerability will be reported in terms of the frequency, severity and nature of adverse events, and the treatment received.
6. Quality of life. Quality of life will be assessed at trial entry and every three months using the questionnaires European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients (EORTC QLQ-C30), EORTC-QLQ-BLS24 (a 24-item questionnaire for patients with superficial bladder cancer) and Euroqol EQ-5D.
7. Cost effectiveness. Patient costs will be calculated and cost-effectiveness assessed. The economic analysis will be based on both a principal outcome cost-per-survivor (disease-free) at 24 months; and a secondary outcome, cost-per-QALY.

All secondary outcomes will be followed-up for 2 years from first treatment.