6. Common treatment schedules
Various chemotherapy and BCG schedules have been described, with contradictory evidence in support of each. The following schedules, however, are most commonly used and it is recommended to follow local guidelines.
Chemotherapy (MMC): A single immediate, postoperative instillation or immediate postoperative instillation followed by six weekly instillations and then, if cystoscopy is negative, monthly instillations for a period of one year [21].
BCG: Administration should start no sooner than two weeks after TURBT and consists of six weekly instillations (induction course) followed by three weekly instillations (maintenance) at 3, 6, 12, 18, 24, 30 and 36 months, provided that cystoscopy and cytology are negative [22]. Maintenance in intermediate-risk patients stops after 12 months [14].
6.1 Device-assisted intravesical chemotherapy
The most commonly used devices are electromotive drug administration (EMDA), radiofrequency induced thermochemotherapeutic effect (RITE) and conductive hyperthermic chemotherapy (HIVEC). The RITE technology has been developed to induce hyperthermia using microwave radiation. With the EMDA technology, an electrical charge is generated between a cutaneous electrode and a catheter electrode to increase the transport of drug molecules into tissue. With HIVEC, the drug is heated externally and then delivered to the bladder. Overall, the evidence base for device-assisted intravesical chemotherapy is growing and the results of further studies are awaited.
6.2 Treatment after failure of intravesical therapy
Several categories of BCG failure have been proposed. NMIBC may not respond at all (BCG refractory) or may relapse after initial response (BCG relapsing). Please refer to the EAU Guidelines on NMIBC [14].
6.3 Alternatives to MMC and BCG
At present, the standard of care for low-risk patients is one immediate instillation of intravesical chemotherapy after TURBT [14]. For intermediate-risk patients in general, chemotherapy is a reasonable first-line option in the majority of patients with one year of full-dose BCG treatment as an alternative option [14]. For high-risk patients, full-dose BCG instillation for one to three years is standard, but immediate RC should be discussed. In BCG-unresponsive patients, RC is recommended [14].
Several trials investigating immune checkpoint inhibitors, targeted therapies, gene therapy, vaccines and alternative and combination chemotherapy regimens are running [23]. At present, however, alternative treatment options remain investigational, and their use is not recommended outside well-designed clinical trials.