STATION 1: UROLOGICAL ONCOLOGY 1 Table 10 ~ Probabilities of recurrence and progression {after 1 year and 5 years} (95% Cl) Recurrence score % Probability % Probability recurrence at 1 year recurrence at 5 years oO 15 31 1-4 24 46 5-9 38 62 10-17 61 78 Progression score ° 02 08 2-6 Z 6 7-13 § 7 14-23, 7 45 Prior disease recurrence rate and number of tumours are the most important prognostic factors for disease recurrence. Stage and grade are the most important factors for disease progression and disease-specific survival. ‘Age and grade are the most important factors for overall survival. as progress to invasive disease in over 50% if not treated. Progression to muscle invasive disease will occur for patients in < 5 % of GipTa, 10% multi-focal G1pT1, 30% G3pT1, 50% of CIS and 50-80% or G3 + CIS disease. MANAGEMENT MITOMYCIN-C ‘Administered as an intra-vesical chemotherapy agent (given 40mg in 40mL of saline over an hour). MMC is an anti-tumour antibiotic causing DNA cross-linking in bladder tumour cells. [1] Systemic toxicity is rare however if irritative LUTS and genito-palmar rash occur then halt treatment. Given as single instillation (S!) within hours (otherwise tumour cells implant and are covered by extra-cellular matrix) after TURBT to destroy circulating tmanue calle and ahlate racidual tumour celle at resection site.NON-MUSCLE INVASIVE BLADI Sylvester et al. (2004) [12] + published meta-analysis of 7 RCTs of TURBT + MMC vs. TURBT alone + single MMC dose within 24 hours of TURBT: RR reduction of recurrence 39%, AR risk reduction of 12% + NNTis 7 (to prevent a recurrence within 5 years) i.e, reduces rate of recurrence but not progression The most recent review suggested S! MMC only benefited those with EORTC score < 5 and recurrence rate of 1 or less per year. For intermediate-risk patients, adjuvant MMC instillations may have an impact on recurrence, however there is no clear defined schedule for duration and frequency for this to be given. HIVEC Trial, is currently comparing hyperthermia + MMC vs, MMC alone, in patients with intermediate risk disease. BCG THERAPY Bacillus Calmette-Guerin (live attenuated mycobacterium bovis) Available strains include Connaught, OncoTice and RIVM with comparable efficacies. “ Mechanism of action poorly understood ~ attaches to urothelium via fibronectin receptor, internalised within the cell, acting as immune stimulant by up-regulating cytokine production (IL-6 and IL-8) within bladder wall and mediating macrophage chemotaxis. Administered via catheter which is removed, patient asked to retain for 2 hours and then void whilst sitting down to avoid contamination and wash hands with bleach. indications Comparable efficacy with MMC for low- and intermediate- risk groups and therefore not recommended first line due to added toxicity risk. In high-risk superficial disease it is recommended. Meta-analysis by Sylvester et al. (2002) of 24 trials and 4800 patients found 27% RR reduction (4% ARR) progression to muscle-invasive disease with maintenance BCG, 2.5 year follow up. [13] Maintenance BCG only (i.e. not induction BCG) will reduce the risk of diseaseMUSCLE-INVASIVE BLADDER CANCER 31 WHO Performance Status Performance status is a score that estimates the ability of the Patient to perform certain activities of daily living without assistance from others, Important factor for determining suitability of treatment as well as. for selection criteria for clinical trials. Table 13 ~ WHO (and ECOG) Performance status [17) Performance Description Status 0 able to carry out all normal activity without restriction 1 restricted in strenuous activity but ambulatory and able to carry out light work 2 ambulatory and capable of al self-care but unable to carry out any work activities; up and about more than 50% of waking hours 3 symptomatic and in a chair or in bed for greater than 50% of the day but not bedridden 4 completely disabled; cannot carry out any self-care; totally confined to bed or chair, Cardio-Pulmonary Exercise Test (CPEX or CPET) CPEX carried ott as outpatient procedure. Patient sits on bicycleAvalks on treadmill and is connected to a 12 lead ECG, blood pressure cuff and pulse oximeter, Three ventilatory variables are measured: + oxygen consumption + carbon dioxide excretion + minute ventilation The exercise resistance is gradually increased over 10-15 minutes. CPEX is a functional assessment of cardiopulmonary reserve and is becoming routine in the preoperative assessment of patients undergoing major surgery (e.g. cystectomy). Anaerobic threshold is the point at which aerobic metabolism is no longer adequate and anaerobic supplementation begins (note that aerobic Pee ae LEE EDSTATION 1; UROLOGICAL ONCO! alization Embolization of the renal artery can be undertaken hours before RN. This procedure can reduce blood loss, allow ligation of the renal vein first and facilitate dissection due to tissue oedema. “Post-infarction syndrome" is the most common complication pain, nausea, fever. ACTIVE SURVEILLANCE AS defined as the initial monitoring of tumour size by serial abdominal imaging (US, CT, MRI) with delayed intervention reserved for tumours showing clinical progression. Watchful waiting implies that patient co-morbidities preclude any future treatment and therefore tumours do not require follow-up imaging. Largest series of AS found growth of renal tumours was low and metastatic progression 1-2%. [39] Overall, both short- and intermediate- term oncological outcomes indicate that in selected frail / co-morbid patients, AS is initially appropriate to monitor small renal masses. Lower long-term cancer-specific mortality for patients undergoing surgery. CRYOSURGERY (CS) For tumours < 4cm in size Usually performed under GA, the kidney can be accessed CT-guided (percutaneous), loin incision (open) or laparoscopically +/- concurrent renal biopsy. Involves direct insertion of freezing probes into tumour and two separate freeze / thaw cycles resulting in the formation of an “ice-ball”. ‘Complication rates are comparable for percutaneous vs. laparoscopic techniques. Complications of cryotherapy include: + infection, pain and bleeding requiring transfusion + need for further treatment + pneumothorax requiring insertion of chest drain « iniurv to liver spleen. nancreas. bowel. maior vessels