Recirculant hyperthermic IntraVEsical chemotherapy (HIVEC) in intermediate-high-risk non-muscle-invasive bladder cancer.

Purpose To examine the effectiveness of hyperthermic intravesical chemotherapy (HIVEC™) with mitomycin-C (MMC) for patients with intermediate-high-risk non-muscle invasive bladder cancer (NMIBC). Materials and methods From November 2010 to April 2015, 40 patients with intermediate-high-risk NMIBC received HIVEC™ treatment with a Combat BRS system. Of these patients, 24 received neoadjuvant HIVEC™ treatment (eight weekly instillations) before a transurethral resection of the bladder (TURBT) and 16 received adjuvant HIVEC™ treatment post-TURBT (four instillations weekly + six monthly). The pathological response of each tumour was evaluated after the neoadjuvant treatment. Recurrence rates and adverse effects were evaluated in both groups. Results A total of 40 patients completed the induction therapy: 24 patients received the Neoadjuvant HIVEC™ treatment. Of these patients, 15 (62.5%) showed a complete response. Eight patients (33.3%) showed a partial response, and one patient (4.1%) showed no response at all. The 4-year cumulative incidence of recurrence was 20.8%. The adjuvant HIVEC™ treatment was given to 16 patients. The 2-year cumulative incidence of recurrence was 12.5% for this group. The incidence and severity of side effects were slightly lower in the adjuvant group than in the neoadjuvant group. However, the difference was not statistically significant (p < 0.3). Most of the side effects were low grade and had virtually no effect on the treatment plan, and 97% of patients completed all of the HIVEC™ instillations scheduled. Conclusions The recirculation of hyperthermic MMC using Combat's HIVEC™ treatment is safe and effective and is capable of achieving good success rates in both neoadjuvant and adjuvant settings. This treatment seems to be appropriate for NMIBC intermediate-high-risk patients who cannot tolerate or have contraindications for standard BCG therapy or in cases in which there are supply issues or shortages of BCG.

[Analysis of budgetary impact of moderate and high risk non muscle-invasive bladder cancer by means of neoadjuvant hyperthermia chemotherapy compared to the standard adjuvant treatment with BCG]. / Análisis del impacto presupuedtario del tratamiento mediante quimiohipertermia neoadyuvante en el cáncer vesical no muúculo invasive.

OBJECTIVES: To study the relationship between cost-effectiveness and budgetary impact the application of a neoadjuvant chemo-hyperthermia treatment on 15 patients with NMI multi-recurrent bladder cancer and/or whose risk of recurrence and progression is medium-high, compared with the standard neoadjuvant BCG treatment, has had on the Hospital Comarcal de Monforte de Lemos (Lugo). METHODS: A model was designed from an SNS perspective with a temporary horizon of three years to compare the costs of applying neoadjuvant chemo-hyperthermia on the patients of the clinical test (8 instillations weekly of 80 mg Mitomycin C recirculating at 43 C for an hour prior to carrying out a transurethral resection of the bladder tumor) with the costs of treating 15 patients with the same risk profile with the standard adjuvant treatment of BCG (control group). The effective available costs corresponding to drugs, disposables and those relative to TURBT, cold biopsy and tumor relapse were included. The costs of diagnostic tests and follow-up were discarded from the model because they did not vary between groups. RESULTS: The model built with effective and published cost data establishes a favourable difference in favour of the neoadjuvant treatment with chemo hyperthermia in terms of 3 year costs with a minimum global savings of 10,300€ and 687€ per patient, together with an improvement in the effectiveness of the treatment. These values could reach a minimum savings of 25,960€ and 1,731€ per patient, if a change in protocol is made after the neoadjuvant treatment, which uses the cold biopsy to check the results. Of the 15 patients pre-treated with chemo-hyperthermia, 11 high-risk and 4 medium-risk, 9 have responded completely (absence of residual tumor) and 6 partially (shrinking of the tumor). The number of expected relapses has been reduced from 8 to 2 and progression from 3 to 0. CONCLUSIONS: The neoadjuvant treatment with chemo hyperthermia constitutes a cost-effective therapeutic strategy.

Análisis del Impacto Presupuestario del tratamiento mediante quimiohipertermia neoadyuvante en el cáncer vesical no músculo invasivo / Analysis of Budgetary Impact of moderate and high risk non muscle-invasive bladder cancer by means of neoadjuvant hyperthermia chemotherapy compared to the standard adjuvant treatment with BCG

OBJETIVO: Estudiar la relación de coste-efectividad e impacto presupuestario de una pauta de quimiohipertermia (QHT) neoadyuvante en pacientes con cáncer vesical no musculo invasivo (NMI) comparándolo con un tratamiento estándar de BCG y aplicando valores de recidiva y progresión basadas en tablas de riesgo internacionalmente aceptadas. MÉTODOS: Para ello, se diseñó un modelo desde la perspectiva de un sistema público de salud tras un seguimiento de 3 años para comparar los costes de aplicar quimiohipertermia neoadyuvante a los pacientes del ensayo clínico (8 instilaciones semanales de 80 mg Mitomicina C recirculando a 43 ºC durante 1 hora previas a la realización de una resección transuretral del tumor vesical) con los costes de tratar a 15 pacientes con el mismo perfil de riesgo con el tratamiento estándar adyuvante de BCG (grupo control). Se incluyeron los costes reales disponibles correspondientes a fármacos y desechables y los publicados relativos a la resección transuretral (RTU) de vejiga, biopsia fría y riesgo de recidiva tumoral. Se descartaron del modelo los costes de pruebas diagnósticas y de seguimiento por no variar entre ambos grupos. RESULTADOS: El modelo construido con datos de costes reales y publicados establece una diferencia favorable para el tratamiento neoadyuvante con quimiohipertermia en términos de coste a 3 años con un ahorro mínimo global de 10.300€ y de 687€ por paciente, todo ello con una mejora de la efectividad del tratamiento. Estos valores pueden pasar a 25.960€ de ahorro mínimo y 1.731€ de ahorro por paciente, si se asume un cambio de protocolo después de la neoadyuvancia que utilice la biopsia fría para comprobar el resultado. De los 15 pacientes pretratados con quimiohipertermia, 11 de riesgo alto y 4 de riesgo medio, 9 han respondido de forma completa (ausencia de tumor residual) y 6 de forma parcial (reducción del tumor). El número de recurrencias esperadas se ha reducido de 8 a 2 y de progresiones de 3 a 0. CONCLUSIONES: El tratamiento neoadyuvante con quimiohipertermia constituye una estrategia terapéutica coste-efectiva

OBJECTIVES: To study the relationship between cost-effectiveness and budgetary impact the application of a neoadjuvant chemo-hyperthermia treatment on 15 patients with NMI multi-recurrent bladder cancer and/or whose risk of recurrence and progression is medium-high, compared with the standard neoadjuvant BCG treatment, has had on the Hospital Comarcal de Monforte de Lemos (Lugo). METHODS: A model was designed from an SNS perspective with a temporary horizon of three years to compare the costs of applying neoadjuvant chemohyperthermia on the patients of the clinical test (8 instillations weekly of 80 mg Mitomycin C recirculating at 43° C for an hour prior to carrying out a transurethral resection of the bladder tumor) with the costs of treating 15 patients with the same risk profile with the standard adjuvant treatment of BCG (control group). The effective available costs corresponding to drugs, disposables and those relative to TURBT, cold biopsy and tumor relapse were included. The costs of diagnostic tests and followup were discarded from the model because they did not vary between groups. RESULTS: The model built with effective and published cost data establishes a favourable difference in favour of the neoadjuvant treatment with chemo hyperthermia in terms of 3 year costs with a minimum global savings of 10,300€ and 687€ per patient, together with an improvement in the effectiveness of the treatment. These values could reach a minimum savings of 25,960€ and 1,731€ per patient, if a change in protocol is made after the neoadjuvant treatment, which uses the cold biopsy to check the results. Of the 15 patients pre-treated with chemo-hyperthermia, 11 high-risk and 4 medium-risk, 9 have responded completely (absence of residual tumor) and 6 partially (shrinking of the tumor). The number of expected relapses has been reduced from 8 to 2 and progression from 3 to 0. CONCLUSIONS: The neoadjuvant treatment with chemo hyperthermia constitutes a cost-effective therapeutic strategy

A clinical trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) for treating intermediate and high-risk non-muscle invasive bladder cancer.

PURPOSE: Ths paper reports a pilot/feasibility trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) prior to transurethral resection of bladder tumour (TURBT) for non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A pilot/feasibility clinical trial was performed and 15 patients with intermediate to high-risk NMIBC received HIVEC prior to TURBT. HIVEC consisting of eight weekly instillations of intravesical MMC (80 mg in 50 mL) delivered with the novel Combat BRS® system at a temperature of 43 °C for 60 min. Treatment-related adverse effects were measured and patients were followed for 2 years for disease recurrence. RESULTS: A total of 119 HIVEC treatments occurred. Grade 1 adverse events consisted of irritative bladder symptoms (33%), bladder spasms (27%), pain (27%), haematuria (20%) and urinary tract infection (UTI; 14%). Grade 2 adverse events were bladder calcification (7%) and reduced bladder capacity (7%). No grade 3 or higher toxicity was observed. At TURBT, eight patients (53%) were complete responders (pT0) while seven (47%) were partial responders. With a median follow-up of 29 months, the 3-year cumulative incidence of recurrence was 15%. CONCLUSIONS: The Combat BRS® system achieved target bladder temperatures and delivered HIVEC with a favourable side-effect profile. Our pilot trial also provides preliminary evidence of treatment efficacy.