Long term results failed to show a significant benefit with LTAD compared to STAD in patients treated with HDRT. The subgroup of patients with high-risk PCa treated with LTAD had a non-significant improvement in bDFS, MFS and OS compared with STAD. The relatively small simple size, a low number of events and an effective salvage treatment could be responsible for the lack of a statistical significance. The trial is registered at ClinicalTrials.gov, number NCT02175212.

Clinical trials have reported conflicting findings on the role of D plus ADT in p with mCSPC according to extent of disease. We have retrospectively analyzed the impact of extent of disease on progression-free survival (PFS) and overall survival (OS) in p with mCSPC treated with D plus ADT or ADT alone in clinical practice. Between 2015 and 2019, 160 p with mCSPC were treated at centers of the Catalan Institute of Oncology (Catalunya, Spain). For the present study, we have classified these p according to extent of disease. Those with ≥five bone metastases and/or visceral metastases were defined as "high-volume" (HV; n=87), and all other p were defined as "low-volume" (LV; n=73). One hundred p (60 HV; 40 LV) received D plus ADT and 60 p (27 HV; 33 LV) received ADT alone. Median age was 69.5 years; 79% of p were ECOG PS 0-1; 81% had Gleason 8-10. Bone, lymph node, and visceral metastases were present in 87%, 66%, and 15% of p, respectively. p receiving ADT alone were older with poorer ECOG PS than p receiving D plus ADT. 95 p (59%) progressed to castration-resistant prostate cancer, 74% of whom were then treated with abiraterone or enzalutamide and 24% with D or cabazitaxel. Median PFS was 18.9 months (m) in the 100 p treated with D plus ADT and 13.4 m in the 60 p treated with ADT alone (P=0.01). Among LV p, PFS was longer in those receiving D plus ADT than those receiving ADT alone (29.6 m vs 15.0 m; P=0.002). In contrast, in HV p, no differences in PFS according to treatment were observed. Although OS was slightly longer in p treated with D plus ADT (39.2 m vs 35.7 m, p=0.26), the difference was not significant either in HV p (P=0.41) or LV p (P=0.11). Multivariate analyses identified advanced age, PS 2, HV, and ADT alone as markers of shorter PFS and only PS 2 as a marker of shorter OS. Despite the limitations inherent in a retrospective, non-randomized study, our findings suggest a benefit in PFS for D plus ADT in LV p but not in HV p. A longer follow-up and marginal structural modeling are warranted to determine the impact on OS in both HV and LV p.

A relationship between inflammatory markers and cancer progression has been suggested. Several studies in different types of tumors have found that NLR and PLR are associated with prognosis. A high NLR was linked to shorter OS in p with metastatic castration-resistant prostate cancer. However, the role of NLR and PLR in mCSPC has not been explored. We have examined the potential prognostic impact of NLR and PLR in p with mCSPC treated with D plus ADT. We retrospectively analyzed 100 p with mCSPC treated with D plus ADT from 2015 to 2019 at centers of the Catalan Institute of Oncology (Catalunya, Spain). For the present study, we have classified these p according to extent of disease. Those with ≥five bone metastases and/or visceral metastases were defined as "high-volume" (HV; n=60), and all other p were defined as "low-volume" (LV; n=40). We explored the association of pretreatment NLR and PLR with OS in all p and in the HV and LV subgroups. Pretreatment NLR and PLR were successfully determined in 95 p. 67 p (70%) had low NLR (<3) and 28 p (30%) had high NLR (≥3), while 53 p (56%) had low PLR (<130) and 42 (44%) had high PLR (≥130). No significant differences in OS were observed according to NLR. p with high PLR showed a non-significant trend towards longer OS than those with low PLR (not reached [NR] vs 36.7 months; P=0.09). The multivariate analysis identified NLR (HR 0.34; 95% CI 0.1-1.2; P=0.09) and PLR (HR 0.32; 95% CI 0.12-0.90; P=0.03) as independent markers of OS. In the subgroup of LV p, there were no differences in OS according to PLR, but in HV p, there was a trend towards longer OS among p with high PLR (P=0.08). In contrast with previous studies, we have found that both high PLR and high NLR may have an effect on longer OS in mCSPC p treated with D plus ADT. Results were confirmed in the subgroup of HV p but not in that of LV p.

espanolOBJETIVO: El objetivo de este estudio es describir la experiencia inicial en nuestro centro de las primeras 94 Biopsias de Prostata dirigidas (BD) con fusion de imagen ecografia/Resonancia magnetica (US/RMmp) y comparar la tasa de deteccion de CaP con las biopsias sistematicas. MATERIAL Y METODOS: Se realizo un estudio retrospectivo, descriptivo y comparativo de los primeros 94 pacientes sometidos a BD por fusion de imagen US/RMmp en nuestro centro desde febrero de 2017 hasta marzo de 2018. Todos los pacientes fueron sometidos a un protocolo de 6-12 cilindros de biopsias sistematicas (BS) (menos 9) y de 2-6 cilindros dirigidos a las lesiones diana visualizadas en la RMmp. Se utilizo el equipo Hitachi/HiVision Preirus con software RVS (Real-time virtual sonography) y un transductor biplanar para la fusion de imagen. Se definio como CaP clinicamente significativo un GS ≥ 3+4 en, al menos, 1 de los cilindros realizados. RESULTADOS: La proporcion de deteccion de CaP fue mayor en las BD que en las BS (p=0,035) y el numero de cilindros realizados para su diagnostico fue menor en las BD comparado con las BS (p CONCLUSIONES: Comparado con las BS, las BD por fusion de imagen US/RMmp presentaron una mayor tasa de deteccion de CaP y una tendencia a una mayor identificacion de CaPcS con una necesidad menor de cilindros realizados. EnglishOBJECTIVE: To describe the initial experience in our center on targeted prostate biopsies (TB) using Magnetic Resonance imaging/ultrasonography (MRI/US) fusion and to compare PCa detection with systematic biopsies (SB). PATIENTS AND METHODS: A retrospective, descriptive and comparative study was conducted on the first 94 men who underwent TB using MRU/US fusion in our center since February 2017 to March 2018. All patients underwent a protocol of 6-12 cores of systematic biopsies (SB) (except 9) and 2-6 targeted cores on the MRI index lesion. The Hitachi/HiVision Preirus equipment was used with RVS software (Real-time virtual sonography) and a biplane transducer for the fusion imaging procedure. Clinically significant PCa (csPCa) was defined as: at least one core with a Gleason score of 3+4. RESULTS: The proportion of patients diagnosed with PCa was higher in TB compared with SB (p=0.035) and the mean of core performed for diagnosis was lower in TB compared with SB (p CONCLUSIONS: The MRI/US fusion targeted biopsies (TB) showed a higher detection rate of PCa, with less cores taken for diagnosis and a tendency to better identification of csCaP compared to SB.

Introducción y objetivoEl síndrome de retirada de abiraterona (SRA) se caracteriza por un descenso transitorio de PSA tras la discontinuación del tratamiento con acetato de abiraterona (AA) en los pacientes diagnosticados de cáncer de próstata resistente a castración metastásico (CPRCm). El objetivo de nuestro estudio es identificar posibles factores predictivos al diagnóstico que puedan influir en el SRA.Materiales y métodosSe realizó un estudio retrospectivo de los pacientes que recibieron tratamiento con AA en el Institut Català d’Oncologia - L’Hospitalet entre 2015 y 2017, obteniendo una muestra de 70 pacientes.ResultadosPresentaron SRA 11 pacientes. La edad media al diagnóstico fue 65,73 años y la edad media de presentación 74,18 años. El número de ciclo de tratamiento fue el noveno. La mediana de PSA al diagnóstico fue de 30,5ng/ml; la mediana de PSA en el SRA, 33,24ng/ml; y la mediana de PSA antes de iniciar otro tratamiento, 15,78ng/ml. La media de seguimiento tras SRA fue de 8,2 meses. Los factores predictivos del SRA serían PSA elevado (p=0,002), ISUP≥4 (p=0,002) y estadio IV al diagnóstico (p<0,001). El estadio T presenta un riesgo elevado, pero sin significación estadística. Se obtuvo una ABC ROC de 0,84, con un IC 95% entre 0,77 y 0,92 (p<0,001).ConclusionesLa incidencia del SRA no es despreciable, describiendo respuestas prolongadas tras la retirada del AA, incluso la posibilidad de una mejoría en la supervivencia global. Estos resultados podrían suponer un cambio en el esquema de tratamiento del CPRCm.

INTRODUCTION AND OBJECTIVE:Abiraterone withdrawal syndrome (AWS) is characterized by a transient decrease in the PSA after abiraterone acetate (AA) treatment discontinuation in patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC). The aim of our study is to identify the possible predictive factors of AWS at diagnosis. MATERIALS AND METHODS:We performed a retrospective study of 70 patients treated with AA at the Institut Català d'Oncologia - L'Hospitalet between 2015 and 2017. RESULTS:11 patients presented AWS. The mean age at diagnosis was 65.73 years and the mean age of presentation was 74.18 years. Patients were in the ninth treatment cycle. The median PSA was: 30.5ng/ml at diagnosis, 33.24ng/ml in the AWS, and 15.78ng/ml before starting another treatment. The median follow-up period after AWS was 8.2 months. The predictive factors of AWS would be: high PSA (p=.002), ISUP≥4 (p=.002) and stage IV at diagnosis (p<.001). Patients with a T stage present high risk, but without statistical significance. An AUC of 0.84 was obtained, with a 95% CI between 0.77 and 0.92 (p<.001). CONCLUSIONS:The incidence of AWS is not negligible, describing prolonged responses after AA withdrawal, including the possibility of increased overall survival. These results could entail new treatment schemes for mCRPC.

We compared biochemical control and quality of life with intermittent (6 months) versus continuous (36 months) androgen deprivation therapy (ADT) in a non-inferiority randomized phase 3 trial in patients with biochemical failure (BF) after external beam radical radiotherapy (EBRT).

Dose escalation in prostate cancer showed an increase in toxicity in several normofractionation trials. The low alpha beta ratio of prostate cancer seems to make appropriate dose escalation with extreme hypofractionation. To compare toxicity and Quality of Life (QoL) of two regimens (SBRT alone 85 GyEqD2 or SBRT as a boost 87GyEqD2) of hypofractionated stereotactic body radiation therapy (SBRT) with intensity modulated arc therapy (IMAT). Two prospective phase I-II SBRT studies in prostate cancer, approved by our institutional review and ethics board were used. Hormonal-therapy was prescribed according to risk classification. Image Guided RT with Cone Beam CT was mandatory. Dose SBRT was delivered at a prescribed planning target volume (PTV) 35 Gy in five fractions in 5 alternative days (Trial 1)or 9 Gy after 60 Gy 2 Gy per fraction in 30 days (Trial 2), using with RapidArc IMAT, with 6 MV FFF photons. CTCAE v4.0 morbidity scores were used to assess toxicities. Health-related quality of life questionnaire, such as EPIC, was administered centrally by telephone interview before treatment and during follow-up (at 3, 6 and 12 months). Comparison of dosimetric parameters by t-student test, toxicities by Wilcoxon rank sum test and QoL values by confidence intervals were done between the two groups of patients. Forty patients have been recruited. Mean age was 70.2 years. Twenty-two patients were included in trial 1 and 18 in trial 2. According to D'Amico risk classification for trial 1), 3/22 patients were low-risk and 19/22 were intermediate risk, for trial 2) 18 patients were high risk. All patients completed the treatment as programmed with good tolerance. Median follow-up was 15 months (3-41). Prostate, urethral, bladder and rectal volumes are not statistically different between groups. No toxicity greater than grade 2 was observed. Acute GU and GI grade 2 toxicities were higher in trial 1 for week after treatment 40.9% vs 27.8 % and 36.4% vs 11.1%. At the 1st month GI Grade 2 toxicity was also higher for trial 1, 36.4% vs trial 2, 13.6%. No significant differences were found in GU or GI toxicities during follow-up between groups. EPIC urinary, EPIC incontinence and EPIC obstructive QoL values were significantly better at 6 and 12 moths for trial 1 vs trial 2. No differences were seen in EPIC bowel values. Considering a median follow-up period of 15 months, dose escalation to 85 (EqD2)Gy or to 87 (EqD2)Gy showed a different early toxicity profile, time factor with longer overall treatment time in the higher dose (trial 2) may modulate this fact. Low dose showed significantly better QoL urinary function. Longer follow-up is needed to validate these results.

To report toxicity of pelvic VMAT with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with high-risk or very high risk prostate cancer. Eighty-three consecutive patients (pts), diagnosed with high risk or locally advanced prostate cancer, were treated between June 2011 and May 2015 with SIB-VMAT. All of them also received androgen suppression. On the planning-CT CTV1 (prostate), CTV2 (CTV1 plus seminal vesicles) and CTV3 (CTV2 plus pelvic nodes) were delineated. CTVs were expanded to generate the planning target volumes (PTV). The VMAT plans were designed to deliver 67,5 Gy in 27 fractions (2.5 Gy/fr) to the prostate, 59,4 Gy (2,2Gy/fr) while delivering simultaneously 48.6 Gy in 27 fractions(1.8 Gy/fr) to the pelvic lymph nodes. In pts with N1, dose was increased to 59.4 Gy at 2.2 Gy given simultaneously, and HDR brachytherapy 9 Gy/1 fr was done in unfavorable dosimetry for integrated boost to the prostate. Toxicity was scored by CTCAEv4.0. Univariate and multivariate analysis were performed looking for correlations among patient characteristics, dose values and toxicity. Median age of patients (pts) was 70 years old. Gleason score was >=8 in 70% of pts. The median follow-up was 30 months (from 6 to 50 months). All received the prescribed external radiation dose in 27 fractions. Sixty-two patients received 67.5 Gy to the CTV1 plus margin at 2.5 Gy per fraction. Brachytherapy boost was performed in 21 pts delivering 9 Gy in one fraction over 59.4 Gy at 2.2 to the CTV2 plus margin. Four pts died (one for a second tumor and the other three for prostate cancer progression). The most common acute event was urinary frequency/urgency (90%). Acute urinary toxicity was scored as 1 in 70% of pts. Rectal acute toxicity grade 2 (G2) with mucosal discharge was present in 40% of pts. No late toxicity exceeding G2 was rectal toxicity G2 or less was 25%. Urinary toxicity G2 or less was 40%. G2 acute or late bowel toxicity was seen in 8% and 4% respectively. G2 acute or late bowel toxicity was not associated with bowel volume receiving V30, V40, V50, or V60Gy. Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. Pelvic VMAT with SIB or sequential HDR brachytherapy to the prostate were well tolerated in this series, with acceptable rates of acute and subacute toxicity. SIB-VMAT combines pelvic radiation therapy and hypofractionation to the primary site and offers an accelerated approach to treating high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression.

1) To evaluate the feasibility and toxicity of two regimens of hypofractionated stereotactic body radiation therapy (SBRT). 2) To obtain patients (pts) self-reported quality of life (QOL) measures in two cohorts of SBRT and to compare with a LDR-Brachytherapy for intermediate risk prostate cancer and HDR brachytherapy boost after 60Gy of external radiation EBRT for high risk pts. Two prospective phase I-II studies were approved by our institutional review and ethics board. Inclusion criteria were: Trial1) T1-2N0M0, Gleason Score 6–7, PSA ≤ 20 ng/mL, and IPSS 0–7. Trial 2) T3aN0M0, Gleason score 8 or less (N+risk<25%) and IPSS 12 or less. Hormonal-therapy was prescribed according to risk classification. Image Guided RT with Cone Beam CT was mandatory. Dose SBRT was delivered at a prescribed planning target volume (PTV) 35 Gy in 5 fractions in 5 alternative days or 9 Gy after 60 Gy 2 Gy per fraction in 30 days, using with volumetric modulated arc therapy (VMAT), with 6 MV FFF photons. CTCAE v4.0 morbidity scores were used to assess toxicities. Health-related quality of life questionnaires, such as EPIC and SF-36, were administered centrally by telephone interview before treatment and during follow-up (at 3, 6 and 12 months). Comparison of QLQ values was done between Trial 1 pts and a cohort of 280 LDR brachytherapy pts and external radiation combined plus HDR brachytherapy 9 Gy boost in 88 pts vs Trial 2 pts. Twenty-nine pts have been recruited. Mean age was 70.6 years. Eighteen pts were included in trial 1 and 11 in trial 2. According to D'Amico risk classification for trial 1), 3/18 pts were low-risk and 15/18 were intermediate risk, for trial 2) 11 pts were high risk. All pts completed the treatment as programmed with good tolerance. No toxicity greater than grade 2 was observed. Acute GU and rectal toxicities were seen in 20/29 (69%) and 17/29 (18.6%) pts respectively. Both GU and rectal late toxicities G2 were: 2/29 (6.9%) and 1/29 (3.4%). EPIC urinary values were significantly better at 3 and 6 months for SBRT (5x7) vs LDR brachytherapy and EPIC hormonal was higher at 3, 6 and 12 months in LDR brachytherapy group, whereas in 9 Gy boost pts EPIC hormonal was lower at 0 and 3 months in SBRT group. Values on both bowel and sexual did not showed differences. SF-36 values were significantly better for brachytherapy pts (general health, mental health, vitality). Early findings indicate that both SBRT regimes with VMAT and FFF beams for low–intermediate-risk prostate cancer and high risk are feasible and well tolerated in selected pts. Although EPIC hormonal and some SF-36 QLQ measures are worse in SBRT pts than brachytherapy cohorts, EPIC values related to radiation treatment are not different. Long-term follow-up is needed for assessment of late toxicity and outcomes.

We present secondary endpoints of late toxicity from a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term androgen deprivation (STAD) when combined with high-dose radiotherapy (HDRT) in prostate cancer (PCa). The hypothesis is that LTAD does not increase radiation-induced toxicity compared to STAD. Three hundred fifty-five eligible men with cT1c-T3aN0M0 PCa with intermediate and high-risk factors according to 2005 NCCN criteria were randomized to 4 months of androgen deprivation (AD) combined with HDRT median dose 78 Gy (STAD), or the same treatment followed by 24 months of AD (LTAD). Treatment related complications were assessed using EORTC-RTOG and CTCAEs v3.0 scoring schemes. Cumulative incidence of toxicity was calculated according to the product-limit (Kaplan-Meier) method. A logistic regression analysis was performed to identify prognostic factors affecting the risk of late rectal, urinary, and cardiovascular (CV) side effects. Median follow-up was 63 months. The 5-year incidence of grade ≥2 rectal and urinary toxicity was 10.7% and 8.4% for LTAD and 7.8% and 7.8% for STAD, respectively. Compared to STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal (OR = 0.721, 95% CI = 0.337-1.542, P = 0.399) and urinary (OR = 1.015, 95% CI = 0.469-2.195, P = 0.970) toxicity. On multivariate analysis, a baseline history of intestinal comorbidity (OR = 4.103, 95% CI = 1.722-9.772, P = 0.001), and the VR60 (OR = 1.039, 95% CI = 1.002-1.077, P = 0.039) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous bladder and prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (OR = 2.912, 95% CI = 1.145-7.409, P = 0.025). The 5-year cumulative incidence of a CV event was 17.9% and 7.4% for LTAD and STAD, respectively (P = 0.025). LTAD (OR = 2.032; 95% CI = 1.086-3.802, P = 0.027) and the antecedent of myocardial infarction (OR = 2.476; 95% CI = 1.245-4.924, P = 0.010) were independent factors associated with a higher risk of CV events. The results of this trial showed that LTAD did not significantly impact urinary or rectal radiation-induced toxicity in PCa patients treated with HDRT, although it was associated with a higher risk of non-fatal CV events. Longer follow-up is needed to ascertain the magnitude of the influence of AD on late morbidity and non PCa mortality.