ABSTRACT
BACKGROUND AND OBJECTIVE: To assess the medium-term tumor control in patients with localized prostate cancer (PCa) treated with vascular-targeted photodynamic (VTP) therapy with TOOKAD Soluble WST11 (VTP) and to assess the medium-term tolerability of the treatment. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: During the clinical phase II studies, 68 patients were treated with VTP under optimal treatment conditions (WST11 at 4mg/kg, light energy at 200J/cm, and a light density index ≥1) and have been included in a 3.5-yr follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-interventional visits were scheduled every 6 mo and conducted as per local standard practice in each study center. Cancer-free status was assessed by means of prostate-specific antigen kinetics, multiparametric magnetic resonance imaging and/or prostate biopsies. RESULTS AND LIMITATIONS: At the end of the 3.5-yr follow-up, overall successful focal ablation was achieved for 51 patients (75%). Cancer was identified in the untreated lobe in 17 patients (25%). In total, 34 patients (50%) were cancer-free in both the prostate lobes. In case of recurrent/persistent malignancy, the Gleason score remained consistent or changed at the maximum by one point (upgrading by 1 Gleason point to 3+4 for eight patients and 4+3 for two patients). There were 64 related adverse events (AEs): 48% were Clavien grade I, 47% were grade II, and 5% were grade III. There were no Clavien grade IV and V AEs. Limitations included small sample size and heterogeneity in the follow-up for some centers. CONCLUSIONS: VTP is a safe and efficient treatment and represents an alternative option for localized low-risk PCa management over the medium term. Precise diagnostic methods and imaging tools are thereby essential requirements to ensure safe and complete targeted therapy. PATIENT SUMMARY: In this report, we looked at the medium-term outcomes of focal photodynamic therapy for early-stage prostate cancer. We found that this form of treatment is efficient and might have the potential to become a therapeutic option for low-risk cancer. Effectiveness depends on precise diagnostic methods, such as magnetic resonance imaging and accurate biopsy.
Subject(s)
Bacteriochlorophylls/therapeutic use , Photochemotherapy/methods , Prostatic Neoplasms/therapy , Aged , Bacteriochlorophylls/administration & dosage , Biopsy , Combined Modality Therapy/methods , Follow-Up Studies , Humans , Male , Middle Aged , Molecular Targeted Therapy/methods , Multiparametric Magnetic Resonance Imaging/methods , Neoplasm Grading/methods , Photochemotherapy/adverse effects , Prostate/blood supply , Prostate/pathology , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood supply , Prostatic Neoplasms/pathology , Risk Assessment , Treatment OutcomeABSTRACT
Objetivos: Explorar la proporción de pacientes con cáncer de próstata localizado (CaP) de mayor riesgo que se convertiría en una biopsia negativa con seguridad 12 meses después de la terapia focal no térmica con terapia fotodinámica dirigida vascular de padeliporfina (TFV). Métodos: Estudio multicéntrico en un escenario de antígeno prostático específico (PSA) ≤ 20 ng/ml y patrón 3 de Gleason de volúmenes objetivo de CaP variable o patrón 4 de Gleason secundario de volumen bajo. Todos los pacientes recibieron TFV, que consistió en 4 mg/kg de padeliporfina intravenosa activada por fibras difusoras de luz en la próstata. La próstata se biopsió al inicio del estudio y a los meses 6 y 12. El PSA, los resultados funcionales informados por los pacientes y los cuestionarios de calidad de vida (CdV) se registraron al inicio y a los meses 3, 6 y 12; los eventos adversos (EA) se registraron a lo largo del estudio. Resultados: En la población con intención de tratar (n = 81), la proporción de pacientes con biopsias negativas al mes 12 fue del 74% (60/81 pacientes, IC 95%: 63,1, 83,2%). En la población por protocolo, la proporción fue del 79% (58/73 pacientes, IC 95%: 68,4, 88,0%). Los resultados del cuestionario indicaron una ligera mejoría en la función urinaria y un deterioro limitado en la función sexual. No se observó diferencia en la CdV con el tiempo. Un total de 42/81 (52%) pacientes comunicaron EA leves o moderados y 4 de 81 (4,9%) experimentaron EA graves, todos resueltos sin secuelas. No se informó fototoxicidad, evento cardiovascular, fístula o incontinencia urinaria prolongada, cáncer secundario o muerte. Conclusiones: Los resultados respaldan la eficacia, la seguridad y la CdV asociadas con el tratamiento focal de padeliporfina para el CaP localizado de riesgo bajo/intermedio
Objectives: To explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). Methods: Multicenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. Results: In the intention-to-treat population (n = 81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%, 83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%, 88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. Conclusions: Results support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa
Subject(s)
Humans , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Photosensitizing Agents/administration & dosage , Prostatic Neoplasms/drug therapy , Photochemotherapy/methods , Prostate-Specific Antigen/blood , Treatment Outcome , Follow-Up Studies , Quality of LifeABSTRACT
OBJECTIVES: To explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). METHODS: Multicenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. RESULTS: In the intention-to-treat population (n=81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%,83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%,88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. CONCLUSIONS: Results support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa.
Subject(s)
Bacteriochlorophylls/therapeutic use , Photochemotherapy/methods , Prostatic Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Humans , Latin America , Male , Middle Aged , Prostatic Neoplasms/blood supply , Quality of LifeABSTRACT
Vascular targeted photodynamic therapy (VTP) with WST11 is a novel non-thermal focal treatment for localized prostate cancer that has shown favorable and early efficacy results in previously published studies. In this work, we investigate the efficiency of automatic dosimetric treatment planning. An action model established in a previous study was used in an image-guided optimization scheme to define the personalized optimal light dose for each patient. The calculated light dose is expressed as the number of optical cylindrical fibers to be used, their positions according to an external insertion grid, and the lengths of their diffuser parts. Evaluation of the method was carried out on data collected from 17 patients enrolled in two multi-centric clinical trials. The protocol consisted of comparing the method-simulated necrosis to the result observed on day 7 MR enhanced images. The method performances showed that the final result can be estimated with an accuracy of 10%, corresponding to a margin of 3 mm. In addition, this process was compatible with clinical conditions in terms of calculation times. The overall process took less than 10 min. Different aspects of the VTP procedure were already defined and optimized. Personalized treatment planning definition remained as an issue needing further investigation. The method proposed herein completes the standardization of VTP and opens new pathways for the clinical development of the technique.
