Positive prostate biopsy following radiotherapy can predict metastasis-free survival in localized prostate cancer.

BACKGROUND/AIMS: To determine the impact of post-treatment biopsy results on 10-year metastasis-free survival (MFS), overall survival (OS) and cause-specific survival (CSS) in localized prostate cancer (PCa) patients treated with high-dose radiotherapy (RT). MATERIALS/METHODS: Retrospective analysis of 232 patients with T1c-T3bN0M0 PCa who underwent a prostate biopsy 24-36 months after high-dose RT. Biopsies were categorized as positive biopsy (PB) if H&E staining showed evidence of residual malignancy and negative biopsy (NB) if no malignant cells were present. Kaplan-Meier estimates of 10-year MFS, OS and CSS rates were calculated for each group and Cox proportional-hazards models were used to estimate the hazard ratios. The median follow-up was 124 months (range 26-267). RESULTS: Sixty-two of 232 (26.7%) patients had post-treatment positive biopsies (PB). A positive post-treatment biopsy was significantly associated with a lower 10-year MFS (78.4% vs. 95.4%, p = 0.001, HR: 3.9, 95% CI: 1.8-8.3). Although patients with PB had worse outcomes that those with NB, we could not show a statistically significant difference in OS (81.0% vs. 87.9%, p = 0.282, HR: 1.3, 95% CI: 0.7-2.3) or CSS (96.2% vs. 99.4% (p = 0.201, HR. 2.4, 95% CI: 0.6-9.7). After multivariate analysis, the strongest predictor of MFS was the post-treatment biopsy status (p < 0.001, HR: 5.4, 95% CI 2.26-12.85) followed by Gleason score (p = 0.002, HR: 2.24, 95% CI 1.33-3.79). CONCLUSION: A positive biopsy following RT can predict MFS in localized prostate cancer. These data highlight the relevance of achieving a local control and support the use of aggressive local therapeutic interventions for PCa.

Reduced late urinary toxicity with high-dose intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer

Background/purpose. To evaluate the impact of intensity-modulated radiotherapy (IMRT) with intra-prostate fiducial markers image-guided radiotherapy (IGRT) on the incidence of late urinary toxicity compared to 3D conformal radiotherapy (3DCRT) for patients with prostate cancer (PC). Methods and materials. We selected 733 consecutive patients with localized PC treated with dose-escalation radiotherapy between 2001 and 2014. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up 24 months. 438 patients were treated with 3DCRT and 295 with IMRT. Acute and late urinary complications were assessed using the EORTC/RTOG and CTCAEs v3.0 definition. The Cox regression model was used to compare grade ≥2 urinary toxicity between both techniques. The median follow-up was 75 months (range 24-204). Results. The median isocenter radiation dose was 78.7 Gy for 3DCRT and 80.7 Gy for IMRT/IGRT (p < 0.001). The 5-year incidence of late grade ≥2 urinary toxicity was 6.4% for IMRT and 10.8% for 3DCRT [hazard ratio (HR) 0.575, p = 0.056]. The corresponding 5-year estimates of late grade ≥2 hematuria were 2% for IMRT and 5.3% for 3DCRT (HR 0.296, p = 0.024). On multivariate analysis, the antecedent of prior transurethral resection of the prostate was also a strong predictor of a higher risk of urinary complications (HR 2.464, p = 0.002) and of hematuria (HR 5.196, p < 0.001). Conclusion. Compared with 3DCRT, high-dose IMRT/IGRT is associated with a lower rate of late urinary complications in spite of higher radiation dose (AU)

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Reduced late urinary toxicity with high-dose intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer.

BACKGROUND/PURPOSE: To evaluate the impact of intensity-modulated radiotherapy (IMRT) with intra-prostate fiducial markers image-guided radiotherapy (IGRT) on the incidence of late urinary toxicity compared to 3D conformal radiotherapy (3DCRT) for patients with prostate cancer (PC). METHODS AND MATERIALS: We selected 733 consecutive patients with localized PC treated with dose-escalation radiotherapy between 2001 and 2014. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up 24 months. 438 patients were treated with 3DCRT and 295 with IMRT. Acute and late urinary complications were assessed using the EORTC/RTOG and CTCAEs v3.0 definition. The Cox regression model was used to compare grade ≥2 urinary toxicity between both techniques. The median follow-up was 75 months (range 24-204). RESULTS: The median isocenter radiation dose was 78.7 Gy for 3DCRT and 80.7 Gy for IMRT/IGRT (p < 0.001). The 5-year incidence of late grade ≥2 urinary toxicity was 6.4% for IMRT and 10.8% for 3DCRT [hazard ratio (HR) 0.575, p = 0.056]. The corresponding 5-year estimates of late grade ≥2 hematuria were 2% for IMRT and 5.3% for 3DCRT (HR 0.296, p = 0.024). On multivariate analysis, the antecedent of prior transurethral resection of the prostate was also a strong predictor of a higher risk of urinary complications (HR 2.464, p = 0.002) and of hematuria (HR 5.196, p < 0.001). CONCLUSION: Compared with 3DCRT, high-dose IMRT/IGRT is associated with a lower rate of late urinary complications in spite of higher radiation dose.

[Dose escalation with three dimensional conformal radiotherapy for prostate cancer: more is better?]. / Intensificación de dosis con radioterapia conformacional 3D en cancer de próstata. Mas dosis es mejor?

PURPOSE: The present study was undertaken to determine the effect of radiation dose on biochemical control and morbidity in prostate cancer patients. MATERIALS AND METHODS: Between 1995 and 2003, 360 patients with T1-T3b prostate cancer were treated in a sequential radiation dose escalation trial from 66.0 to 82.6 Gy. These patients were prospectively assigned to 1 of 3 prognostic groups according to risk factors: a) low risk patients were treated with 3DCRT alone; b) intermediate risk patients were allocated to receive neoadjuvant AD (NAD) 4-6 months prior and during 3DCRT; and c) high-risk received NAD and adjuvant AD (AAD) 2 years after 3DCRT. RTOG/EORTC toxicity score was used to analyze late complications RESULTS: Median follow-up was 48 months (12-138). The actuarial biochemical disease free survival (bDFS) at 4 years for low risk, intermediate risk and high risk patients was 88%, 68% and 79% respectively. Stratified and multivariate analysis showed that higher radiation dose (>76 Gy) (p=0.0053) and the use of AAD for high risk patients (p=0.0046) correlated significantly with an improvement of bDFS for all patients. The incidence of late grade 2 rectal and urinary bleeding were 7% and 11% respectively. CONCLUSION: The present study confirms an independent benefit of high-dose (> 76 Gy) radiation therapy and long-term AAD in high-risk prostate cancerpatients.

Intensificación de dosis con radioterapia conformacional 3D en cáncer de próstata. ¿Más dosis es mejor? / Dose escalation with three dimensional conformal radiotherapy for prostate cancer: more is better?

Objetivo: Determinar el efecto de la dosis de radiación en los resultados de control bioquímico y morbilidad en pacientes con cáncer de próstata. Material y Métodos: Entre 1995 y 2003, 360 pacientes con cáncer de próstata T1-T3b fueron tratados conRTC3D (66,0 Gy-82,6 Gy). Los pacientes fueron asignados a uno de tres grupos pronósticos: a) bajo riesgo: tratados con RTC3D exclusiva; b) riesgo intermedio tratados con deprivación androgénica (DA) neoadyuvante 4-6meses previos y durante RTC3D; y c) alto riesgo: DA previa, durante y dos años tras RTC3D. Para el análisis de toxicidad tardía se empleó la escala de RTOG/EORTC. Resultados: Con una mediana de seguimiento de 48 meses (12-138), la supervivencia libre de fracaso bioquímico (SLFB) a 4 años en pacientes de bajo riesgo fue del 88%, en los de riesgo intermedio fue del 68% y en los de alto riesgo del 79%. En el análisis estratificado del efecto de la dosis de RTC3D controlado por el uso de hormonoterapia, y en el análisis multivariante, tanto la dosis alta de irradiación (>76 Gy) (p=0,0053), como el empleo de DA durante dos años en alto riesgo (p=0,0046) se correlacionan de forma independiente con un mejor control bioquímico. La incidencia de sangrado rectal y urinario grado 2 fue del 7% y 11% respectivamente. Conclusión: Estos datos confirman que tanto la RTC3D a dosis altas como la asociación de DA en pacientes de alto riesgo contribuyen de forma independiente a mejorar de forma significativa los resultados del tratamiento de los pacientes con cáncer de próstata (AU)

Purpose: The present study was undertaken to determine the effect of radiation dose on biochemical control and morbidity in prostate cancer patients. Materials and Methods: Between 1995 and 2003, 360 patients with T1-T3b prostate cancer were treated in a sequential radiation dose escalation trial from 66.0 to 82.6 Gy. These patients were prospectively assigned to 1 of 3 prognostic groups according to risk factors: a) low risk patients were treated with 3DCRT alone; b) intermediate risk patients were allocated to receive neoadjuvant AD (NAD) 4-6 months prior and during 3DCRT; and c) highrisk received NAD and adjuvant AD (AAD) 2 years after 3DCRT. RTOG/EORTC toxicity score was used to analyze late complications. Results: Median follow-up was 48 months (12-138). The actuarial biochemical disease free survival (bDFS) at 4 years for low risk, intermediate risk and high risk patients was 88%, 68% and 79% respectively. Stratified and multivariate analysis showed that higher radiation dose (>76 Gy) (p=0.0053) and the use of AAD for high risk patients (p=0.0046) correlated significantly with an improvement of bDFS for all patients. The incidence of late grade 2 rectal and urinary bleeding were 7% and 11% respectively. Conclusion: The present study confirms an independent benefit of high-dose (> 76 Gy) radiation therapy and long-term AAD in high-risk prostate cancer patients (AU)