Role of psa levels and pathological stadiation before radiation therapy in predicting mp-MRI results in patients with prostate cancer recurrence after radical prostatectomy.

OBJECTIVE: To evaluate PSA value in mp-MRI results prediction, analyzing patients with high (GS≥8, pT≥3, pN1) and low grade (GS<8, pT<3, pN0) Prostate Cancer (PCa). MATERIALS AND METHODS: One hundred eighty-eight patients underwent 1.5-Tmp-MRI after Radical Prostatectomy (RP) and before Radiotherapy (RT). They were divided into 2 groups: A and B, for patients with biochemical recurrence (BCR) and without BCR but with high local recurrence risk. Considering Gleason Score (GS), pT and pN as independent grouping variables, ROC analyses of PSA levels at primary PCa diagnosis and PSA before RT were performed in order to identify the optimal cut-off to predict mp-MRI result. RESULTS: Group A and B showed higher AUC for PSA before RT than PSA at PCa diagnosis, in low and high grade tumors. For low grade tumors the best AUC was 0.646 and 0.685 in group A and B; for high grade the best AUC was 0.705 and 1 in group A and B, respectively. For low grade tumors the best PSA cut-off was 0.565-0.58ng/mL in group A (sensitivity, specificity: 70.5%, 66%), and 0.11-0.13ng/mL in B (sensitivity, specificity: 62.5%, 84.6%). For high grade tumors, the best PSA cut-off obtained was 0.265-0.305ng/mL in group A (sensitivity, specificity: 95%, 42.1%), and 0.13-0.15ng/mL in B (sensitivity, specificity: 100%). CONCLUSION: Mp-MRI should be performed as added diagnostic tool always when a BCR is detected, especially in high grade PCa. In patients without BCR, mp-MRI results, although poorly related to pathological stadiation, still have a good diagnostic performance, mostly when PSA>0.1-0.15ng/mL.

European Association of Urology biochemical recurrence risk groups after radical prostatectomy: External validation and identification of independent risk factors for progression and death.

BACKGROUND: The EAU proposed a progression and death risk classification in patients with biochemical recurrence after radical prostatectomy (PR). OBJECTIVE: To validate the EAU BCR-risk classification in our setting and to find factors related to progression and death. MATERIAL AND METHODS: Multicenter, retrospective, observational study including 2140 patients underwent RP between 2011 and 2015. Patients with BCR were identified and stratified in low risk (PSA-DT >1yr and pGS <8) or high-risk (PSA-DT ≤1yr or pGS ≥8) grouping. PSA and metastatic free survival (PSA-PFS, MFS), cancer specific survival (CSS) and overall survival (OS) were calculated (Kaplan Meier curves and log-rank test). Independent risk factors were identified (Cox regression). RESULTS: 427 patients experienced BCR (32.3% low-risk and 67.7% high-risk). Median PSA-PFS was 135,0 mo (95% CI 129,63-140,94) and 115,0 mo (95% CI 104,02-125,98) (p<0,001), for low and high-risk groups, respectively. There were also significant differences in MFS and OS. The EAU BCR risk grouping was independent factor for PSA-progression (HR 2.55, p 0.009). Time from PR to BCR, was an independent factor for metastasis onset (HR 0.43, 95% CI 0.18-0.99; p 0.044) and death (HR 0.17, 95% CI 0.26.0.96; 23 p 0.048). Differences in MFS (p 0.001) and CSS (p 0.004) were found for <12, ≥12-<36 and ≥36 months from PR to BCR. Others independent factors were early salvage radiotherapy and PSA at BCR. CONCLUSIONS: High-risk group is a prognostic factor for biochemical progression, but it has a limited accuracy on MP and death in our setting. The inclusion of other factors could increase its predictive power.

Open retropubic radical prostatectomy: Still a well-established surgical technique for prostate cancer management.

INTRODUCTION: The surgical treatment options for prostate cancer have changed rapidly, given the expansion of robotics. However, open retropubic radical prostatectomy (ORP) will continue to be performed in areas with financial limitations or with limited access to robotics. The purpose of this study was to determine the long-term oncological outcomes, to categorize complication rates and to examine the early continence rates in patients treated with ORP. METHODS: We identified all patients who underwent ORP at our institution between 2000 and 2020. A standardized pad test was used to determine the early continence rates upon catheter removal, the late continence around a year after surgery was determined by the number of pads per day. The Clavien-Dindo classification was used to report the complication rates. The biochemical recurrence (BCR)-free survival and overall survival (OS) rates were defined using the Kaplan-Meier method and log-rank analysis. Multivariable Cox-regression models were used to test the effect of different factors on biochemical recurrence. RESULTS: We analyzed 1095 patients. The median follow-up was 93.4 months. An overall 10-year BCR-free survival and OS of 73% and 82% respectively was found. A complication rate for Clavien Dindo≥3 was seen in 4.8% of patients. The early continence rate was 81.4% and the late continence 89,1%. Preoperative PSA level, Gleason score sum, pT stage, lymph node status, and surgical margin status were independent predictors of BCR (p<0.001, 95% CI). Limitations include retrospective and single center study design. CONCLUSIONS: ORP is a surgical procedure that provides excellent oncological- and early continence-rates.

The role of multiparametric mri in the diagnosis of local recurrence after radical prostatectomy and before salvage radiotherapy.

PURPOSE: Assess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of Prostate Cancer (PCa) after Radical Prostatectomy (PR) and before Radiation Therapy (RT). MATERIALS AND METHODS: A total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into two groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between two groups using T-Student; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables. RESULTS: PCa recurrence (reduction of PSA levels after RT) was 89.8% in the group A and 80.3% in the group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. DWI is the most specific MRI-sequence and DCE the most sensitive. For PSA = 0.5 ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA = 0.9 ng/ml, DCE-AUC increases significantly. CONCLUSION: mp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of DWI for PSA ≤ 0.5 ng/ml.

[CAPRA score vs minimal residual disease as predictors of biochemical recurrence after radical prostatectomy.] / La puntuación CAPRA frente a los subtipos de enfermedad residual mínima para predecir la recidiva bioquímica después de la prostatectomía radical.

OBJECTIVE: To compare the classification CAPRA (based on clinical-pathological findings) and minimal residual disease (MRD) (based on biological characteristics) to predict biochemical failure (BF). METHOD AND PATIENTS: The clinical-pathological findings of the prostate biopsy were used to determine the CAPRA score, classifying patients into low, intermediate and high risk. Blood and bone marrow samples to detect circulating prostate cells (CPCs) and micro-metastasis were taken. The samples were classified as positive if ≥1 prostate cell was detected, forming three subgroups; Group A (MRD negative), Group B (micro-metastasis positive, CPC negative) and Group C (CPC positive). Patients were followed-up for 10 yearsor BF. Kaplan-Meier biochemical failure free survival (BFFS) curves, a predictive flexible parameter survival model and mean restricted survival times (MRST) were determined. RESULTS: 347 men participated, BF risk increased with increasing CAPRA score, HR 1.21 intermediate, 1.64 high risk; versus MRD HR 1.91 and 4.43 for Groups Band C. After 10 years the BFFS and MRST were 76%, 50% and 17% and 9, 7 and 5 years respectively for CAPRA versus 94%, 57% and 26% and 10, 9 and 6 years respectively for MRD. The concordance between observed and predicted BFFS was acceptable for CAPRA (Harrell´s C 0.64) and very good (0.92) for MRD. The BFFS curves for MRD were not proportional with time, they were similar for 5 years for Groups A and B, with increasing BFFS in Group B there after.The CAPRA score did not distinguish between Groups A and B, one third of low risk CAPRA patients had CPCs detected. CONCLUSIONS: The MRD classification was superior to CAPRA, differentiating between early and late failure.

OBJETIVO: Comparar la puntuación CAPRA (en función de los hallazgos clínico-patológicos) y la enfermedad residual mínima (ERM) (en función de las propiedades biológicas) para predecir la recidiva bioquímica (RB).MÉTODOS Y PACIENTES: Los hallazgos clínico-patológicos de biopsias de próstata determinaron la puntuación CAPRA definiendo pacientes de bajo, intermedio y alto riesgo de la RB. Se obtuvieron muestras de sangre y médula ósea para detectar CPCs (Células Prostáticas Circulantes) y micro-metástasis usando inmunocitoquímica. Se clasificaron como positivas si se detectaba ≥1 célula en la muestra. Se formaron tres subgrupos: Grupo A (ERM negativo), Grupo B (micro-metástasis positivo, CPC negativo) y Grupo C (CPC positivo). Los pacientes fueron seguidos durante diez años o hasta la RB. Las curvas de supervivencia libre de recidiva bioquímica (SLRB) se construyeron usando el método de Kaplan Meier, un modelo de parámetro flexible (supervivencia predecida) y el tiempo de supervivencia medio restringido (TSMR) para cada subgrupo. RESULTADOS: 347 hombres participaron; el riesgode RB aumentó proporcionalmente; HR 1,21 riesgo intermedio,1,64 riesgo alto para CAPRA versus 1,91 Grupo B y 4,43 Grupo C para EMR. Después de diez años, el SLRB y el TSMR fueron 76%, 50%, 17% y 9,7 y 5 años respectivamente para CAPRA versus 94%, 57%, 26% y 10, 9 y 6 años respectivamente para EMR. El acuerdo entre SLRB observada y prevista fue aceptable para CAPRA (Harrell´s C 0,64) y muy buena (0,92) para EMR. Las curvas SLRB para la EMR no fueron proporcionales; para Grupos A y B fueron similares hasta cinco años, luego hubo una falla creciente en el Grupo B. La puntuación de CAPRA no logró distinguir entre los Grupos A y B, un tercio del Grupo C de alto riesgo tenía una puntuación CAPRA de bajo riesgo. CONCLUSIONES: La clasificación ERM fue superior de la CAPRA, diferenciando entre la RB temprana y tardía.

Comparison between laparoscopic and open prostatectomy: Oncological progression analysis. / Comparación entre prostatectomía laparoscópica y abierta: análisis de la evolución oncológica.

INTRODUCTION: There are very few Spanish studies that compare oncological outcomes following radical prostatectomy (RP) based on surgical approach, and their methodology is not appropriate. OBJECTIVE: To compare oncological outcomes in terms of surgical margins (SM) and biochemical recurrence (BR) between open radical prostatectomy (ORP) and laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODS: Comparison of two cohorts (307 with ORP and 194 with LRP) between 2007-2015. Surgical margin status was defined as positive or negative, and BR as a PSA rise of >0.4 ng/ml after surgery. To compare the qualitative variables, we employed the Chi-squared test, and ANOVA was used for quantitative variables. We performed a multivariate analysis using logistic regression to evaluate the predictive factors of SM, and a multivariate analysis using Cox regression to evaluate the predictive factors of BR. RESULTS: Gleason 7 (3+4) was determined in the surgical specimens of 43.5% of patients, and 31.7% had positive SM. The most frequent pathological stage was pT2c, on the 61.9% of the cases. No significant differences were found between both groups, except for extracapsular extension (p=0.001), more frequent in LRP. The median follow-up was 49 months. BR was seen in the 23% of patients, without significant differences between groups. In the multivariable analysis, only the D'Amico risk group behaved as an independent predictive factor of positive SM, and Gleason score and positive SM acted as independent predictive factors of BR. CONCLUSION: The surgical approach did not influence SM status or BR.

Survival analysis of patients with prostate cancer and unfavorable risk factors treated with radical prostatectomy and salvage radiotherapy after biochemical recurrence and persistence. / Análisis de supervivencia de los pacientes con cáncer de próstata con factores patológicos desfavorables tratados con prostatectomía radical y radioterapia de rescate tras la recidiva y persistencia bioquímica.

OBJECTIVE: Survival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP). MATERIALS AND METHODS: Retrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥8, pathologic stage ≥pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4ng/ml. A survival analysis using Kaplan-Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. RESULTS: Mean follow up: 72 (IQR 27-122) months, mean time to BR: 42 (IQR 20-112) months, mean PSA level at BR: 0.56 (IQR 0.42-0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients. Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15years were 99.1%, 98.1% and 96.6%. Only time to BR <24months (HR=2.55, P=.01) was identified as an independent risk factor for RFS after SRT. CONCLUSIONS: In these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence >24months responded better to rescue treatment.

Usefulness of 18F-Choline Positron Emission Tomography - Computed Tomography in the therapeutic management of patients with biochemical recurrence of prostate adenocarcinoma treated with brachytherapy. / Utilidad de la tomografía de emisión de positrones / tomografía computarizada con 18F-colina en el manejo terapéutico de pacientes con recidiva bioquímica de adenocarcinoma de próstata tratados con braquiterapia.

OBJECTIVE: The objective of the study was to evaluate the usefulness of 18F-choline PET/CT in biochemically recurrent prostate cancer patients treated with brachytherapy, as well as to assess the changes in therapeutic management derived from its outcome. MATERIAL AND METHODS: Retrospective study of 20 patients between 51 and 78 years old, with a history of prostate adenocarcinoma that had been treated with brachytherapy and presented biochemical recurrence (PSA 3.1-12 ng/ml) and staging tests (CT and bone scan) without alterations, were included. The findings visualized in the PET/CT scan with 18F-choline were correlated with the histopathology and/or the evolution of the PSA after therapy. RESULTS: 18F-choline PET/CT scan only detected local recurrence in 15 patients. Local and regional recurrences were seen in 4 patients, and 1 patient presented local and bone recurrence. Local recurrence detected in PET was confirmed by anatomopathological studies in 85% of the cases. In one patient, these findings (PET scan) turned out to be prostatitis, and it could not be confirmed in another patient. Of the cases with local and regional recurrence, local recurrence was histologically confirmed in 3 out of 4 patients. 18F-choline PET/CT changed the therapeutic management in 25% of the patients, discarding the initially planned salvage surgery in 3 cases, 1 radiotherapy and 1 brachytherapy. CONCLUSION: 18F-choline PET/CT could be a useful technique in the group of patients with biochemical recurrence after brachytherapy, providing locoregional and distant involvement findings which had not been detected with conventional imaging tests, thus determining a more adequate therapeutic management.

Diagnostic utility and therapeutic impact of PET/CT [18F]F-Fluoromethylcholine -Choline in the biochemical recurrence of prostate cancer. / Utilidad diagnóstica e impacto terapéutico de la PET/TC con [18F]F-Fluormetilcolina en la recidiva bioquímica del cáncer de próstata.

OBJECTIVE: To assess the diagnostic capability of PET/CT with [18F]F-Fluoromethylcholine in prostate cancer (PC) with biochemical recurrence and its therapeutic impact. MATERIAL AND METHODS: We included 108 patients, diagnosed with PC with biochemical criteria for recurrence. A PET/CT Choline scan was performed by dynamic pelvic and whole body study at 60min post-tracer injection. The relationship between the positive studies and the PSA value was analysed by classifying patients into three groups (<1.2/1.2-2/>2ng/ml), and the diagnostic capacity was assessed with respect to pelvic MRI and the impact on the therapeutic decision. RESULTS: The location of recurrence was identified in 85 of 108 patients (78.7%): 34 local, 47 pelvic lymph nodes and 58 distant lesions, including retroperitoneal, mediastinal lymph nodes and distant organ lesions (bone and lung). Second tumors were diagnosed in 4 patients. No significant differences were found in the percentage of positive studies depending on primary treatment. Patients with PSA>2ng/ml showed a higher percentage of disease detection than patients with a lower PSA level, with significant differences (p<0.0001). PET/CT [18F]F-Choline was able to detect local disease, not previously known from MRI, in 29.41% of patients. PET/CT Choline had an impact on therapeutic management in 67 of 108 patients (62%). CONCLUSIONS: PET/CT with [18F]F-Fluoromethylcholine is a useful tool in the detection of locoregional and disseminated disease of PC treated with suspicion of recurrence, providing a change in therapeutic management in 62% of patients.

[Prostate cancer pathologic features in men ≤55 years treated with robot assisted radical prostatectomy.] / Características clínicopatológicas del cáncer de próstata en varones ≤55 años tratados mediante prostatectomía radical robótica.

OBJECTIVE: Among western males, prostate cancer is the most frequent oncological disease. Since the widespread of PSA, diagnoses in younger adults is increasing. The aim of this study is to analyze pathological features and biochemical recurrence event in patients ≤55 years who underwent robotic radical prostatectomy (RRP) surgery. MATERIAL AND METHODS: A study with a cohort of 510 patients operated between November 2012 and February 2017 in a tertiary centre is provided. A total of 460 are included in the analysis. Variables include PSA, biopsy Gleason score, prostate weight, final specimen Gleason score, pT and surgical margins. Biochemical recurrences during the follow-up are obtained. Statistical analysis with Chi2, Student's t test, Kaplan-Meier and log-rank (SPSS24.0) comparing the ≤55 years patients with older age group is performed. RESULTS: 8.3% (38) of the patients were ≤55 years. The mean PSA among the younger group was 8.54ng/ml while in the older was 8.18ng/ml (p=0.13). The biopsy Gleason scores showed similar distribution in both age groups. 52.6% (20) of the young group presented an upgrading in the final Gleason, vs 49.1% (207) among the elderly (p=0.79). The average prost at eweight was higher among elderly patients (54.29g vs.40.50g P=0.001). 84.2% (32) of prostate cancers in young group corresponded to pT2 stages compared to 81.3% (343) in the elder (p=0.66). The presence of positive surgical margins was similar in both groups. The mean follow-up time was 45 months regardless of age. In 21.1% (8) of the young group, biochemical recurrence was detected compared to 17.1% (72) among the elderly (p=0.53). There were no differences in the biochemical recurrence-free survival recorded in both groups (p=0.53). CONCLUSION: In our study population, patients  ≤55 years treated with RRP did not present differences in the pathologic features of prostate cancer or in biochemical recurrence rates in comparison to the group of older patients.

OBJETIVO: Entre los varones occidentales, el cáncer de próstata es la patología oncológica más frecuente. Con la difusión del PSA, los diagnósticos en adultos jóvenes han ido en aumento. El objetivo de este trabajo es analizar las características clínicopatológicas y la aparición de recidiva bioquímica en pacientes  ≤55años intervenidos mediante prostatectomía radical robótica (PRR).MATERIAL Y MÉTODOS: Se elabora un estudio con una cohorte de 510 pacientes operados entre noviembre 2012 y febrero 2017 en un centro terciario. Un total de 460 son incluidos en el análisis. Se registran variables que incluyen PSA, score Gleason de la biopsia, peso  de la próstata, score Gleason de la pieza, estadio patológico y márgenes quirúrgicos. Se obtienen las recidivas bioquímicas registradas durante el seguimiento. Se realiza un análisis estadístico con los test Chi2, T-Student, Kaplan-Meier y Log-Rank (SPSS24.0) comparando a los pacientes ≤55 años con el grupo de más edad. RESULTADOS: El 8,3% (38) de los pacientes eran ≤55años. El PSA medio entre los jóvenes fue 8,54 ng/ml mientras que en los mayores fue 8,18ng/ml (p=0,13). Los score Gleason descritos en las biopsias mostraron similar distribución en ambos grupos de edad. Tras el estudio anatomopatológico de la pieza quirúrgica, un 52,6% (20) de los jóvenes sufre upgrading en el Gleason, superior al 49,1% (207) registrado entre los mayores (p=0,79). El peso medio de la próstata fue mayor entre los pacientes añosos (54,29g vs. 40,50g P=0,001). El 84,2% (32) de los cánceres de próstata en jóvenes correspondían a estadios T2 frente al 81,3% (343) en los mayores (p=0,66). La presencia de márgenes quirúrgicos positivos fue similar en ambos grupos. El tiempo medio de seguimiento fue 45 meses con independencia de la edad. En el 21,1% (8) de los jóvenes se detectó recidiva bioquímica frente al 17,1%(72) presentado entre los mayores (p=0,53). No hubo diferencias en la supervivencia libre de recidiva bioquímica registrada en ambos grupos (p=0,53).CONCLUSIÓN: En nuestra población de estudio, los pacientes ≤55 años tratados con PRR no presentan diferencias en las características clinicopatológicas del cáncer de próstata ni en la aparición de recidiva bioquímica respecto al grupo de pacientes más mayores.

Value of 18F-Choline PET/MRI hybrid technique on the therapeutic approach for patients with prostate cancer treated with prostatectomy and rising prostate specific antigen levels below 1 ng/ml. / Impacto de la tecnología híbrida PET/RM con 18F-colina en la estrategia terapéutica de los pacientes con cáncer de próstata tratados con prostatectomía que presentan elevación del antígeno prostático específico inferior a 1 ng/ml.

OBJECTIVE: To assess the detection rate of 18F-Choline PET/MRI and subsequent changes in therapy approach for patients with prostate cancer treated by prostatectomy and with rising levels of PSA <1 ng/ml. METHODS: Prospective study with our first 36 patients with prostatectomy for prostate cancer and rising levels of PSA, who were referred for an 18F-Choline PET/MRI study. A dual-phase study was acquired after intravenous administration of 185±10% MBq of 18F-Choline: 1) early imaging (immediately after tracer administration) of prostate area (emission PET/Multiparametric MRI). 2) whole-body imaging 1 h after tracer injection (emission PET/MRI: T1, T2, STIR, diffusion). The therapy approach for patients was decided upon the Oncology Committee consensus based on 18F-Choline PET/MRI findings. RESULTS: Twenty out of 36 patients (55.6%) were positive for the 18F-Choline PET/MRI study: 8 (22.2%) within the prostatectomy bed, 7 (19.4%) with infradiaphragmatic lymph nodes, 4 (11.1%) with local recurrence and infradiaphragmatic lymph nodes, and 1 (2.8%) with bone metastasis. Sixteen out of the 36 patients (44.4%) were negative for the 18F-Choline PET/MRI study. 18F-Choline PET/MRI findings had an impact on the therapy approach to follow: 15 patients (41.6%) showed oligometastatic disease which was treated by imaging-guided radiotherapy, 5 (13.9%) with multiple metastatic disease were treated by androgen deprivation therapy, 16 (44.4%) negative were under active surveillance. CONCLUSION: Hybrid 18F-Choline PET/MRI procedure showed a high detection rate for recurrence in prostate cancer patients treated with prostatectomy and rising PSA levels <1 ng/ml, and 18F-Choline PET/MRI findings resulted in a better tailored therapy approach delivered to our patients.

Usefulness of 18F-fluorocoline PET/CT in prostate cancer patients with biochemical recurrence: Influence of PSA kinetics and hormone therapy. / Utilidad de la PET/TC con 18F-fluorocolina en la recidiva bioquímica del cáncer de próstata: relevancia de la cinética del PSA y la terapia hormonal.

PURPOSE: To evaluate the capacity of 18f-fluorocholine positron emission tomography/computed tomography (FCH PET/CT) to detect biochemical recurrence of prostate cancer and to determine the correlation with PSA kinetics and influence of antiandrogen hormone therapy. PATIENTS AND METHODS: Observational and retrospective study, which included patients with prostate cancer and criteria for biochemical recurrence and/or resistance to castration, according to the European Association of Urology. FCH PET/CT results were classified as positive or negative, using as gold standard the pathology report, findings of other imaging test, and/or clinical follow-up results. The correlation between FCH PET/CT and PSA kinetics (PSA at the time of exploration [PSA-trigger], doubling time [PSAdt] and velocity [PSAva]) was studied and the influence of hormone therapy was analysed. RESULTS: The study included 203 patients. The FCH PET/CT detection rate was 43.3%. The group of patients with FCH PET/CT positive showed more aggressive PSA kinetics (PSAdt: 7.5 months and PSAva 8.37±14.8ng/ml/a) than the FCH PET/CT negative group (PSAdt: 14.5±7.6 months and PSAva: 1.8±3.7ng/ml/a). The detection rate of FCH PET/CT in the subgroup with castration resistance was 89.1%, significantly higher than in the group with radical treatment at 29.9%, p<.001. CONCLUSIONS: FCH PET/CT is useful to detect biochemical recurrence of prostate cancer, especially in patients who receive hormone therapy or more aggressive PSA kinetics.

Predictors of early, intermediate and late biochemical recurrence after minimally invasive radical prostatectomy in a single-centre cohort with a mean follow-up of 8 years. / Factores predictivos de recidiva bioquímica temprana, intermedia y tardía tras prostatectomía radical mínimamente invasiva en una cohorte unicéntrica con seguimiento medio de 8 años.

OBJECTIVE: To determine the predictors of early, intermediate and late biochemical recurrence (BR) following minimally invasive radical prostatectomy in patients with localised prostate cancer (PC). MATERIAL AND METHODS: We included 6195 patients with cT1-3N0M0 prostate cancer treated using radical laparoscopic prostatectomy (RLP) and radical robot-assisted prostatectomy at our institution between 2000 and 2016. None of the patients underwent adjuvant therapy. BR is defined as PSA levels ≥0.2 ng/dL. The time to BR is divided into terciles to identify the variables associated with early (<12 months), intermediate (12-36 months) and late (>36 months) recurrence. We employed logistic regression models to determine the risk factors associated with each interval. RESULTS: We identified 1148 (18.3%) patients with BR. The median time to BR was 24 months (IQR, 0.98-53.18). The multivariate analysis showed that preoperative PSA levels, lymph node invasion, positive margins and RLP are associated with early recurrence (P≤.029 for all). Laparoscopic surgery was the only predictor of intermediate recurrence (P=.001). The predictors of late recurrence included a pathological Gleason score ≥7, stage ≥pT3, positive margins and RLP (P≤.02 for all). CONCLUSIONS: The patients with high-risk prostate cancer can develop late recurrence and require long-term follow-up. Identifying patients with higher PSA levels and lymph node invasion has an important predictive role in the first year after surgery. The association between RLP and BR warrants further assessment.

Our experience in the management of prostate cancer in renal transplant recipients. / Nuestra experiencia en el manejo del cáncer de próstata en pacientes trasplantados renales.

INTRODUCTION AND OBJECTIVES: The management of Prostate cancer (PCa) in renal transplant recipients (RTR) is challenging and remain controversial. Currently there is no consensus about this condition. The aim of the study was to analyse our experience in the diagnosis and management of PCa in RTR. METHOD: Retrospective monocentric study of a prospective and consecutive database from 2003-2017. Inclusion of RTR diagnosed of PCa. Staging and treatment in agreement with the contemporary guidelines. The main outcome measures included clinical staging, type of treatment, oncological outcomes and follow-up. RESULTS: 1,330 renal transplants were performed (787 males), diagnosed of PCa in 33 RTR (4.2%), mean age 66years±6.3 (51-78). Median PSA was 8.8ng/ml and PSA ratio 0.19. Mean time between renal transplantation and PCa diagnosis 130months±90 (2-236). TREATMENTS: Radical prostatectomy (RP) (n=22; 66.7%), Radiation therapy (RT) with Androgen deprivation therapy (ADT) (n=7; 21.2%), Active surveillance (n=3; 9.1%), ADT (n=1; 3%). No graft loss neither impaired renal function due to PCa treatment was reported. After RP two patients (9.1%) presented biochemical recurrence treated with RT. Remission of the 100%. Mean follow-up was 61months±37 (6-132). CONCLUSIONS: PCa in renal transplant patients can be managed with the same therapeutic options as in the general population. Active surveillance should also be provided in RTR despite being under immunosuppressive therapy.

Contribution of 11C-Choline PET/CT in prostate carcinoma biochemical relapse with serum PSA level below 1 ng/ml. / Aportación de la PET/TC con 11C-colina en la recidiva bioquímica del cáncer de próstata con antígeno específico prostático sérico inferior a 1 ng/ml.

OBJECTIVE: 11C-choline PET/CT has demonstrated good results in the restaging of prostate cancer (PCa) with high serum prostate specific antigen (PSA), but its use in patients with low serum PSA is controversial. Our aim was to evaluate the contribution of 11C-choline PET/CT in patients with PCa, biochemical relapse and PSA <1 ng/ml. MATERIAL AND METHOD: Fifty consecutive patients (mean age: 65.9±5.6 years) with biochemical relapse of PCa and serum PSA <1ng/ml were evaluated retrospectively. PET/CT was performed 20min after intravenous administration of 555-740 MBq of 11C-choline. Minimum follow up time was 30 months. RESULTS: Twenty-one out of 50 patients (42%) had an abnormal 11C-choline PET/CT. In 7 out of 21 patients (14%) tumor was confirmed (4 in prostatic bed, 4 in pelvic lymph nodes, 2 in mediastinal lymph nodes and one synchronous sigmoid carcinoma), and in all cases the initial therapeutic planning was modified. In 2 patients (4%) subsequent tests diagnosed a benign disease (one sarcoidosis, one tuberculosis sequelae) and in 3 patients (6%) they ruled out pathology. The other 9 patients (18%) had no further assessment (7 mediastinal and 4 pelvic lymph nodes). Twenty-nine out of 50 patients (58%) had a normal PET/CT. At 30 months, follow up recurrence was confirmed only in 2 of these patients. CONCLUSIONS: 11C-choline PET/CT proved its usefulness in demonstrating tumor in 14% of patients with BR of PCa and serum PSA <1ng/ml, with therapeutic implications. In 4% of patients a benign condition was detected. A normal 11C-choline PET/CT was associated with a very low rate of recurrence at 30 months.

Role of PET-CT with 18F-fluorocholine in biochemical recurrence after treatment of prostate cancer with curative intent. / Papel de la tomografía por emisión de positrones-tomografía computerizada con 18F-fluorocolina en la recidiva bioquímica tras tratamiento con intención curativa del cáncer de próstata.

OBJECTIVES: To analyse the ability of the PET-CT with 18F-fluorocholine (18F-FCH) to detect disease on biochemical recurrence after treatment with curative intent. To determine the clinical variables that would be able to optimise the test's diagnostic yield. MATERIAL AND METHODS: A retrospective study of PET-CTs with 18F-fluorocholine performed on 61 patients with prostate cancer who had undergone treatment with curative intent and met the criteria for biochemical recurrence. The results of the PET-CT were categorised into positive or negative and were validated using pre-established criteria. The relationship between the result of the PET-CT and the initial PSA nadir, PSA trigger, rising PSA velocity (PSAva) and PSA doubling time (PSAdt). The relationship between the metastatic sites on the PET-CT and the remaining variables was analysed. RESULTS: There was a 34.4% detection rate of the disease. The initial PSA, PSA nadir, PSA trigger and PSAva showed statistically significant differences according to the result of the PET-CT. The best discriminatory cut-off point between a positive or negative PET-CT for PSA trigger and PSAva was 3.5ng/ml and 0.25ng/ml/month respectively. The PSAdt was significantly lower in patients with remote disease compared to patients with localised disease (5.1 vs 16.8 months, P=.01). The probability that the PET-CT would detect remote disease vs localised disease was 3.2 times higher if the PSAdt was under 6 months (80% vs 20%, OR: 3.2, P=.02). In the multivariate analysis, only the initial PSA and not having undergone radical prostatectomy were demonstrated as independent predictive factors of a positive PET-CT result. CONCLUSIONS: The PET-CT with 18F-FCH can detect disease in a high percentage of patients with biochemical recurrence and provides information on its anatomical location. PSA kinetics and the patient's previous treatment are key variables in increasing the test's diagnostic.

Identificação de mutações somáticas em adenocarcinoma de próstata com escore de Gleason 7 e 8 e suas associações com recidiva bioquímica / Identification of somatic mutations in prostate adenocarcinoma with Gleason score 7 and 8 and associations with biochemical recurrence

O câncer de próstata é a neoplasia de maior incidência no gênero masculino, após o câncer de pele não melanoma, com índice de mais de 61 mil novos casos em 2016 (INCA). É um tipo de câncer com características histológicas e genéticas heterogêneas e multifocais. Em geral, é um tumor com comportamento indolente, podendo permanecer assintomático por anos. Já em outros casos, a doença pode progredir rapidamente, com o surgimento de metástases e levar o paciente ao óbito. Apesar do escore de Gleason ser um dos principais métodos de classificação desta neoplasia, sozinho ele não fornece informações precisas sobre o prognóstico, visto que pacientes com o mesmo escore podem apresentar comportamentos clínicos distintos, principalmente em tumores com escores intermediários. Com isso, a identificação de marcadores moleculares torna-se uma estratégia importante para melhor estratificação dos tumores indolentes dos mais agressivos, na avaliação de prognóstico, bem como na predição de resposta à terapia. Neste contexto, nossa proposta foi realizar o rastreamento de alterações somáticas em uma coorte de 43 casos de adenocarcinoma de próstata com escore de Gleason intermediário (escore de Gleason 7 e 8) que tenham ou não apresentado recidiva bioquímica. Para isso, foi realizado o sequenciamento das regiões codificadoras de 58 genes utilizando a plataforma NextSeq (Illumina) partindo de 35 amostras pareadas de DNA de tecido congelado do tumor e leucócitos ou tecido normal adjacente e 8 amostras de DNA de tecido congelado do tumor não pareadas. Identificamos 292 alterações somáticas, 226 classificadas como missense e 65 como LoF (perda de função), utilizando a ferramenta MuTect (Broad Institute). Em média encontramos 7 alterações por caso, variando entre 0 a 91 alterações. Encontramos um maior número de SNVs (alterações pontuais) nos tumores classificados com escore de Gleason 3+4 em relação aos tumores com classificação 4+3, considerando a análise da porção tumoral utilizada no sequenciamento e não o escore da peça tumoral como um todo. Dos 58 genes presentes no painel customizado, 45 apresentaram ao menos uma alteração somática (~78%), e 35 genes apresentaram mutações em mais de uma amostra. Foi observado um enriquecimento de alterações somáticas em genes envolvidos com vias de remodelamento de cromatina. Não identificamos diferenças significativas entre o número e tipo de alterações somáticas nos tumores dos pacientes que apresentaram e não apresentaram recidiva bioquímica. Também não foram encontradas associações entre as alterações somáticas e outras características clinico-patológicas, sugerindo que o perfil heterogêneo deste tumor torna o tratamento personalizado e a busca de marcadores um grande desafio (AU)

Prostate cancer is the most prevalent neoplasm in males after nonmelanoma skin cancer, with a rate of more than 61,000 new cases in 2016 (INCA). This tumor shows multifocal and heterogenous histological and genetic characteristics. In general, it presents an indolent behavior, and may remain asymptomatic for years. In other cases, the disease can progress rapidly, with the appearance of metastases and lead to patient death. Although Gleason score is one of the most important classification system of this neoplasm, alone it does not provide precise information on prognosis, since patients with the same score can present different behaviors, especially in tumors with intermediate Gleason. Thus, the identification of molecular markers becomes an important strategy for stratification of indolent and more aggressive tumors, for prognosis evaluation, as well as for prediction of therapy response. In this context, our proposal was the screening of somatic mutations in a cohort of 43 cases of prostate adenocarcinoma with an intermediate Gleason score (7 and 8) that presented or not a biochemical recurrence. To do this, we sequenced the coding regions of 58 genes using the NextSeq (Illumina) platform using 35 paired DNA samples from frozen tissue and leukocytes or normal adjacent tissue and 8 DNA samples from unpaired tumors. We identified 292 somatic variants, 226 classified as missense and 65 as LoF (loss of function), using MuTect pipeline (Broad Institute). On average, we detected 7 alterations per tumor, ranging from 0 to 91 alterations. We detected a statistically significant higher number of SNVs (single nucleotide variants) in tumor with Gleason score 3+4 compared to 4+3, considering the classification of the tumor sample used for sequencing and not the escore of the tumor as a whole. Of the 58 genes in the custom panel, 45 were affected by at least one somaic alteration (~78%), and 35 of them presented mutations in more than one sample. In addition, we observed an enrichment of somatic mutations in genes involved with pathways related to chromatin remodeling. We did not observe statistically significant differences in the number or type of somatic alterations between tumors from patient that presented or not biochemical recurrence. In addition, we did not observe associations between somatic alterations and clinical and pathological characteristics, suggesting that the heterogeneous characteristic of this tumor challenges the identification of molecular markers and personalized treatment (AU)

The role of radical prostatectomy as an initial approach for the treatment of high-risk prostate cancer. / Papel de la prostatectomía radical como abordaje inicial en el tratamiento del cáncer de próstata de alto riesgo.

CONTEXT: The treatment of high-risk prostate cancer requires a multimodal approach to improve control of the disease. There is still no consensus as to the initial strategy of choice. The aim of this study is to review the results of radical prostatectomy as first step in management of patients with high-risk disease. ACQUISITION OF EVIDENCE: A search was conducted on PubMed of English and Spanish texts. We included those studies that reported the results of radical prostatectomy in patients with high-risk prostate cancer, as well as those that compared radical prostatectomy with other treatment alternatives. The last search was conducted in November 2015. SYNTHESIS OF THE EVIDENCE: The advantages of radical prostatectomy include a better pathological analysis, more accurate staging, better local control of the disease and better follow-up and adjuvant therapy strategies. When compared with external radiation therapy plus hormonal blockade, the patients who underwent prostatectomy had greater chances of healing and longer cancer-specific survival. The patients who most benefit from this approach are younger, have fewer comorbidities and no evidence of organ metastases. CONCLUSIONS: The available scientific evidence to date is not without bias and confounders; however, they appear to favour radical prostatectomy as the initial approach of choice for high-risk prostate cancer.

Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT. / Radioterapia de rescate en pacientes con cáncer de próstata. Planificación, respuesta al tratamiento y pronóstico mediante PET/TC con (11)C-colina.

OBJECTIVE: To assess the prognostic value of the therapeutic response by (11)C-choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. METHODS: The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. RESULTS: (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). CONCLUSION: (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance.

Prediction of biochemical recurrence after radical prostatectomy. New tool for selecting candidates for adjuvant radiation therapy.

OBJECTIVE: To design a risk summation to select patients for adjuvant radiation therapy after prostatectomy. MATERIALS AND METHOD: A retrospective study was conducted on 629 patients with localised prostate cancer (pN0-pNx) who were treated with prostatectomy and with a prostate-specific antigen (PSA) value <0.2ng/mL at 2-3 months. Biochemical recurrence was defined as a PSA >0.4ng/mL. A multivariate Cox regression analysis was performed. A score (0-2) was assigned according to the hazard ratio of the significant variables. The score summation defined the risk summation. RESULTS: A total of 19.7% of the patients were pT3, 24.2% had a Gleason score ≥ 8, and 26.3% had positive surgical margins. The median follow-up was 82 months. Some 26.6% of the patients experienced biochemical recurrence. The identified prognostic variables independent of biochemical recurrence were a Gleason score =7 (4+3) (HR, 2.01; P=.008), a Gleason score ≥ 8 (HR, 3.07; P <.001), a pT3b stage (HR, 1.93; p=.008) and a positive surgical margin (HR, 2.20; P<.001). We assigned 0 points to patients without risk prognosis variables; 1 point to patients with Gleason scores =7 (4+3), pT3b or positive surgical margins; and 2 points to patients with Gleason scores ≥ 8. The patients with a risk summation ≤ 2 had >50% survival free of biochemical recurrence at 5 and 8 years. In contrast, the patients with a risk summation ≥ 3 had <44% survival free of biochemical recurrence. CONCLUSION: The patients with a risk summation ≤ 2 did not benefit from adjuvant radiation therapy, while the patients with a risk summation ≥ 3 might benefit from adjuvant radiation therapy.