Prostatectomía radical citorreductora comparado a no realizar tratamiento local en pacientes con cáncer de próstata metastásico / Cytoreductive radical prostatectomy versus no local treatment in patients with metastatic prostate cancer

Introducción El cáncer de próstata es uno de los cánceres más frecuentes en Chile, con 8157 nuevos casos en 2020. A nivel mundial, 5 a 10% de los hombres presentan metástasis al diagnóstico, y la terapia de deprivación androgénica con o sin quimioterapia es el estándar de cuidado para estos pacientes. El uso de tratamiento local en este contexto tiene una recomendación formal debido a la falta de evi-dencia de alta calidad. Algunos estudios retrospectivos han intentado dilucidar el beneficio de la cirugía sobre el tumor primario en el contexto de la enfermedad metastásica, ya que se ha demostrado que es un tratamiento local eficaz para otras neoplasias metastá-sicas. A pesar de estos esfuerzos, el beneficio de la prostatectomía radical citorreductora como tratamiento local en estos pacientes sigue sin estar claro. Métodos Se realizó una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, que se mantiene mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE y Cochrane, entre otras. Se extrajeron los datos de las revisiones sistemáticas, se volvieron a analizar los datos de los estudios primarios, se realizó un metanálisis y se generó una tabla de resumen de resultados utilizando el enfoque GRADE. Resultados y conclusiones Se identificaron 12 revisiones sistemáticas, que incluían siete estudios primarios en total, ninguno de los cuales era un ensayo alea-torizado controlado. Sólo seis de esos siete estudios primarios se utilizaron en el resumen de resultados. A pesar de la falta de evi-dencia de alta calidad, los resultados de este resumen muestran los beneficios de realizar la cirugía en el tumor primario en términos de mortalidad por cualquier causas, mortalidad específica por cáncer y progresión de la enfermedad. También se observó un bene-ficio potencial en las complicaciones locales relacionadas con la progresión del tumor primario, lo que apoya la realización de esta intervención en pacientes con enfermedad metastásica. La ausencia de recomendaciones formales subraya la necesidad de evaluar los beneficios de la cirugía caso por caso, presentando la evidencia disponibles a los pacientes para un proceso de toma de decisiones compartido, teniendo en cuenta las futuras complicaciones locales que podrían ser difíciles de manejar.

Introduction Prostate cancer is one of the most frequent cancers in Chile, with 8157 new cases in 2020. Worldwide, 5 to 10% of men have metastatic disease at diagnosis, and androgen deprivation therapy with or without chemotherapy is the standard of care for these patients. The use of local treatment in this setting has no formal recommendation due to the lack of high- quality evidence. Some retrospective studies have sought to elucidate the benefit of surgery on the primary tumor in the setting of metastatic disease since it has been proven to be an effective local treatment for other metastatic malignant diseases. Despite these efforts, the benefit of cytoreductive radical prostatectomy as local treatment in these patients remains unclear. Methods We searched Epistemonikos, the largest database of systematic reviews in health, which is main-tained by screening multiple information sources, including MEDLINE, EMBASE, and Cochrane, among others. We extracted data from systematic reviews, reanalyzed data from primary studies, conducted a meta- analysis, and generated a summary results table using the GRADE approach. Results and conclusions We identified 12 systematic reviews, including seven studies in total, none of which was a trial. Only six of those seven primary studies were used in the results summary. Despite the lack of high- quality evidence, the results summary shows the benefits of performing surgery on the primary tumor in terms of all- cause mortality, cancer- specific mortality, and disease progression. There was also a potential benefit in local complications related to the progression of the prima-ry tumor, supporting the implementation of this intervention in patients with metastatic disease. The absence of formal recommendations highlights the need to evaluate the benefits of surgery on a case- by- case basis, presenting the available evidence to patients for a shared decision- making process and considering future local complications that could be difficult to manage.

Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer / 亚洲男科学杂志(英文版)

The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS)#8805; 2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14-2.43, P = 0.008) and 1.95 (95% CI: 1.23-3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.

Efficacy and safety of docetaxel plus hormone therapy in metastatic prostate cancer / 中华泌尿外科杂志

Objective:To evaluate the efficacy and safety of docetaxel plus hormone therapy in metastatic prostate cancer.Methods:From April 2016 to April 2019, 204 cases with bone metastatic prostate cancer in the Second Hospital of Tianjin Medical University were analyzed retrospectively. There were 97 patients responded to hormone therapy including 92 cases with high-burden metastasis (more than 4 bone metastases with one or more beyond the axial skeleton) and 5 cases with low-burden metastasis, with average age of 70 years (range 42-87 years) and median prostate specific antigen (PSA) of 74.1 ng/ml (range 11.0-145.0 ng/ml). Among them, there were 35 patients (36.1%) with a Gleason score of 7 or lower, and 62 patients (63.9%) with a Gleason score of 8 or higher. There were 26 patients suffering from bone pain, with average numerical rating scales(NRS) score of 3.7. In addition, there were 107 patients being resistant to hormone therapy, with average age of 73 years (range 56-83 years), and median PSA of 84.5 ng/ml (range 12.4-490.2 ng/ml), including 32 patients (29.9%) with a Gleason score of 7 or lower, and 75 patients (70.1%) with a Gleason score of 8 or higher. Among them, there were 75 patients suffering from bone pain, with average NRS score of 5.4. All patients received continuous hormone therapy combined with docetaxel (at a dose of 75 mg per square meter of body-surface area every 3w, plus prednisone 5 mg twice a day), and PSA progression-free survival (PSA-PFS), NRS score, pain relief, and adverse events were analyzed. Additional analysis of the correlation between PSA-PFS and subgroups with age, PSA level and Gleason score were performed.Results:For patients with metastatic hormone sensitive prostate cancer (mHSPC), 6 (6.2%) cases only received 1-2 cycles of chemotherapy due to different reasons, and the others received 3-6 cycles(average 4.7)with the median follow-up of 15 months. Of patients who received ≥3 cycles, there were 36 cases presenting PSA progression, with the median PSA-PFS of 22 months, average NRS score decline from 3.9 to 3.0, and pain relief rate of 72.0%(18/25). For patients with metastatic castration-resistant prostate cancer (mCRPC), 9 (8.4%)cases only received 1-2 cycles of chemotherapy, and the others received 3-14 cycles (average 5.6). Of patients who received≥3 cycles, there were 51 cases with PSA progression, with the median PSA-PFS of 11 months, average NRS score decline from 5.6 to 4.4, and pain relief rate of 48.6%(35/72). Subgroup analysis showed a significant correlation between PSA level and PSA-PFS for patients with mCRPC( P=0.026). Age or Gleason score was not significantly correlated to PSA-PFS in mHSPC or mCRPC( P>0.05). For patients with mHSPC, grade 3 or 4 neutropenia occurred in 17 cases(17.5%), nausea and vomiting in 27 cases(27.8%), and fatigue in 25 cases(25.8%). For patients with mCRPC, grade 3 or 4 neutropenia occurred in 24 cases (22.4%), nausea and vomiting in 34 cases(31.8%), and fatigue in 26 cases(24.3%). Allergic reaction and sensory neuropathy toxicity were occasional. Conclusion:Efficacy of docetaxel plus hormone therapy was confirmed in metastatic prostate cancer and adverse events were tolerable.

The radionuclide imaging and therapy for metastatic prostate cancer / 中华泌尿外科杂志

Metastatic prostate cancer is one of the most malignancies and do harm to the health and life expectancy of men. The popularization and application of 68Gallium or 18Fluorine labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) benefit for the excellent diagnostic efficacy, unique value in the diagnosis of metastatic prostate cancer, clinical decision-making guidance, efficacy in monitoring and prognosis evaluation. 223Radium and 177Lu-PSMA radioligand therapy (RLT) could effectively alleviate bone pain, and prolong the overall survival time (OS) as wellas progression-free survival time (PFS) with good safety. In addition, survival of patients with metastatic prostate cancer is expected to be further improved with the advance in the combination therapies with PSMA RLT, androgen-deprivation therapy (ADT), chemotherapy, targeted therapy and immunotherapy.

Clinical value of gene detection in metastatic prostate cancer / 中华泌尿外科杂志

The incidence of prostate cancer has increased over the past several years and it has become a major disease that seriously harms male health. Advanced prostate cancer is a heterogeneous disease with poor outcomes, the median overall survival of advanced prostate cancer usually less than two years. Clinical challenges include determining the optimal sequencing of systemic therapies and implementing biomarker-driven treatment approaches. The emergence of precision treatment has brought about a diagnosis and treatment strategy based on molecular testing, which provides the possibility for the formulation of individualized treatment plans.

Advances in novel hormonal agents for metastatic prostate cancer / 中华泌尿外科杂志

With the economic development and medical progress in China, the incidence of prostate cancer is increasing, and most patients have already developed advanced tumors with poor prognosis when diagnosed. The main cornerstone of treatment for metastatic hormone-sensitive prostate cancer (mHSPC) has always been androgen deprivation therapy (ADT), but most mHSPC will transform into metastatic castration-resistant prostate cancer (mCRPC), how to prolong the time from mHSPC to mCRPC has become a current research hotspot, and several landmark phase 3 clinical trials in recent years have led to rapid changes in patient treatment options, including a variety of drugs with different mechanisms of action (e.g., endocrine therapy, chemotherapy, radiotherapy, immunotherapy, and targeted therapy). This article will focus on the current status and progress of novel endocrine agents in metastatic prostate cancer for clinical use.

High body mass index predicts multiple prostate cancer lymph node metastases after radical prostatectomy and extended pelvic lymph node dissection / 亚洲男科学杂志(英文版)

Our aim is to evaluate the association between body mass index (BMI) and preoperative total testosterone (TT) levels with the risk of single and multiple metastatic lymph node invasion (LNI) in prostate cancer patients undergoing radical prostatectomy and extended pelvic lymph node dissection. Preoperative BMI, basal levels of TT, and prostate-specific antigen (PSA) were evaluated in 361 consecutive patients undergoing radical prostatectomy with extended pelvic lymph node dissection between 2014 and 2017. Patients were grouped into either nonmetastatic, one, or more than one metastatic lymph node invasion groups. The association among clinical factors and LNI was evaluated. LNI was detected in 52 (14.4%) patients: 28 (7.8%) cases had one metastatic node and 24 (6.6%) had more than one metastatic node. In the overall study population, BMI correlated inversely with TT (r = -0.256; P 28 kg m-2 (P 28 kg m-2 (P = 0.048). In our study, overweight and obese patients had a higher risk of harboring multiple prostate cancer lymph node metastases and lower TT levels when compared to patients with normal BMI.

Clinical and oncologic findings of extraprostatic extension on needle biopsy in de novo metastatic prostate cancer / 亚洲男科学杂志(英文版)

This study aimed to explore the clinical and oncologic findings in patients with de novo metastatic prostate cancer (mPCa) and extraprostatic extension (EPE) on biopsy. We retrospectively evaluated data on 630 patients with de novo mPCa between January 2009 and December 2017 in the West China Hospital (Chengdu, China), including evaluating the relationships between EPE and other variables and the association of EPE with survival outcomes by the Chi-square test, Kaplan-Meier curves, and the Cox proportional-hazards model. EPE was found in 70/630 patients, making a prevalence of 11.1%. The presence of EPE on biopsy was associated with higher Gleason scores and higher incidence of neuroendocrine differentiation (NED), intraductal carcinoma of the prostate (IDC-P), and perineural invasion (PNI). Compared with those without EPE, patients with EPE had shorter castration-resistant prostate cancer-free survival (CFS; median: 14.1 vs 17.1 months, P = 0.015) and overall survival (OS; median: 43.7 vs 68.3 months, P = 0.032). According to multivariate analysis, EPE was not an independent predictor for survival. Subgroup analyses demonstrated that patients with favorable characteristics, including negative NED or IDC-P status, Eastern Cooperative Oncology Group (ECOG) score <2, and prostate-specific antigen (PSA) <50 ng ml-1, had worse prognoses if EPE was detected. In patients with PSA <50 ng ml-1, EPE was a negative independent predictor for OS (hazard ratio [HR]: 4.239, 95% confidence interval [CI]: 1.218-14.756, P = 0.023). EPE was strongly associated with other aggressive clinicopathological features and poorer CFS and OS. These data suggest that EPE may be an indicator of poor prognosis, particularly in patients, otherwise considered likely to have favorable survival outcomes.

Pretreatment serum albumin/globulin ratio as a prognostic biomarker in metastatic prostate cancer patients treated with maximal androgen blockade / 亚洲男科学杂志(英文版)

The pretreatment serum albumin/globulin ratio (AGR) has been used as a prognostic biomarker for various cancer types. However, the prognostic value of the AGR for prostate cancer, especially for metastatic prostate cancer (mPCa) after maximal androgen blockade (MAB), remains unclear. The aim of this study was to evaluate the prognostic value of the pretreatment serum AGR for mPCa treated with MAB. This retrospective study included 214 mPCa patients receiving MAB from October 2007 to March 2017. The correlation of the AGR with survival was estimated using Kaplan-Meier analysis and Cox proportional hazards models. The cutoff value of the AGR was 1.45 according to the receiver operating characteristic curve. Kaplan-Meier analysis demonstrated that patients with a low AGR (<1.45) had poor outcomes in terms of progression-free survival (PFS) and cancer-specific survival (CSS). Multivariate Cox analyses showed that the AGR was an independent predictor of PFS (hazard ratio [HR] = 0.642; 95% confidence interval [CI]: 0.430-0.957; P = 0.030) and CSS (HR = 0.412; 95% CI: 0.259-0.654; P < 0.001). Furthermore, in a subset of 79 patients with normal serum albumin levels (≥40.0 g l-1), the serum AGR remained an independent predictor of CSS (P = 0.009). The pretreatment AGR was an independent prognostic biomarker for PFS and CSS in patients with mPCa receiving MAB. In addition, the AGR remained effective for the prediction of CSS in patients with normal albumin levels (≥40 g l-1). However, further prospective studies are needed to confirm our conclusions.

Trigeminal Cave Brain Metastasis from Prostate Adenocarcinoma: Case Report and Review of the Literature

The present study presents the case of a 66-year-old patient diagnosed with prostate adenocarcinoma 4 years earlier and treated with prostatectomy, radiotherapy, chemotherapy and hormonetherapy but still displaying high prostate-specific antigen (PSA) levels. The patient complaints were double vision and headaches. Upon physical examination, he displayed 6th cranial nerve paresis and 5th cranial nerve paresthesia. Amagnetic resonance imaging (MRI) exam was performed, which revealed a mass on the right trigeminal cave. The patient underwent surgical removal of the tumor, and the pathological analysis of the specimen established metastatic prostate cancer as the diagnosis. Brainmetastases fromprostate cancer are extremely rare and mark advanced disease, with immune system failure and blood-brain barrier breach. Prostate-specific antigen levels do not correlate with the possibility of metastatic disease. Prostate adenocarcinoma is the histologic typemost commonly associated with brainmetastases,with themeninges being more frequently affected, followed by the brain parenchyma. The neurological symptoms more often displayed are non-focal, such as headaches and mental confusion. Surgery associated with radiotherapy is the most validated treatment.

Risk of complications and urinary incontinence following cytoreductive prostatectomy: A multi-institutional study / 亚洲男科学杂志(英文版)

Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer (PCa). Urinary incontinence was defined as the use of any pad. CRP had longer operative times (200 min vs 140 min, P < 0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared to the control group. However, both overall (8.82% vs 5.85%) and major complication rates (4.41% vs 2.17%) were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI: 1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01-1.36; P = 0.034). In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.

Treatment strategy for metastatic prostate cancer with extremely high PSA level: Reconsidering the value of vintage therapy / 亚洲男科学杂志(英文版)

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml-1), intermediate (100-999 ng ml-1), and high (≥1000 ng ml-1). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

Experiencia inicial en seguridad, tolerancia y adherencia al uso de docetaxel en pacientes con cáncer de próstata castración sensibles en un centro oncológico nacional / Initial experience in safety, tolerance and adherence to the use of docetaxel in patients with sensitive castration prostate cancer in a national cancer center

INTRODUCCIÓN: El cáncer de próstata (PC) es una enfermedad de alta incidencia y prevalencia (90/100.00 habitantes) y constituye la segunda causa por muerte oncológica en hombres, fenómeno que acontece en su fase metastásica (mPC). El tratamiento estándar en esta etapa corresponde a la terapia de deprivación androgénica (TDA) que produce una respuesta oncológica favorable en términos de descenso del PSA y estabilización y/o regresión de las metástasis. Ésta primera etapa (castración sensible) dura en promedio 2 a 3 años, tras lo cual ocurre una independización tumoral del estímulo androgénico, fenómeno conocido como castración-resistencia (mCRPC). En esta etapa la quimioterapia (QMT) con docetaxel prolonga la sobrevida aproximadamente 4 meses, lo cual en conjunto con otros tratamientos de segunda línea (abiraterona, enzalutamida, etc.) logra alcanzar una sobrevida media desde el diagnostico de mCRPC de 24 meses. Diversos estudios (CHAARTED y STAMPEDE) han demostrado que el inicio de docetaxel junto con TDA en pacientes con mPC castración-sensible (mCSPC) prolongan sobrevida global hasta 17 meses, especialmente si hay alto volumen de enfermedad. El objetivo del estudio es describir las características clínicas, la respuesta oncológica inicial y el perfil de efectos adversos de pacientes con mCSPC sometidos a docetaxel. MATERIALES Y MÉTODOS: Estudio retrospectivo descriptivo entre mayo 2014 a Julio 2017. Se incluyeron pacientes ng/ml (rango 10,8 - 5550) y mediana de seguimiento 6 meses (rango 3 ­ 20). Catorce pacientes tenían Gleason > 8, 18 eran M+ de los cuales 9 eran viscerales. Solo uno recibió tratamiento local previo. La mediana de inicio de QMT fue 3,1 (0 ­ 6,1) meses post inicio TDA.Dieciséis pacientes completaron docetaxel y 4 siguen en curso. No hubo suspensión de QMT por efectos adversos. Los más frecuentes fueron diarrea (8/20), neuropatía (5/20) y vómitos (2/20). La mayoría fue grado 1 y solo tres presentaron complicaciones grado 3 (diarrea, leucopenia y trombocitopenia). No hubo complicaciones grado 4 -5. Diez pacientes alcanzaron un antígeno < 2 ng/ml a las 12 semanas post tratamiento y 7 presentaron recidiva bioquímica durante el seguimiento. Uno tuvo respuesta imagenológica completa, 10 respuesta parcial, 7 estabilidad y 2 mostraron progresión. CONCLUSIONES: El uso de Docetaxel en mCSPC es seguro, presenta escasos efectos adversos (la mayoría de intensidad leve) que no motivan suspensión. El tratamiento con docetaxel exhibe una respuesta prometedora en términos de control de PSA, sin embargo se requiere mayor seguimiento de esta cohorte para evaluar impacto en sobrevida. con mCSPC con enfermedad de alto volumen (metástasis óseas extra-axiales, viscerales o Gleason 9-10) y ECOG 0-1. Los pacientes recibieron TDA y seis ciclos de Docetaxel. Se registraron datos demográficos, clínicos, histopatológicos, PSA, imagenológicos (RECIST V1.1) y toxicidad (NCI CAE 4.0) RESULTADOS: Se incluyeron 20 pacientes, mediana de edad 63 años (rango 49 ­ 75). Mediana PSA de ingreso 267,5 ng/ml (rango 10,8 - 5550) y mediana de seguimiento 6 meses (rango 3 ­ 20). Catorce pacientes tenían Gleason > 8, 18 eran M+ de los cuales 9 eran viscerales. Solo uno recibió tratamiento local previo. La mediana de inicio de QMT fue 3,1 (0 ­ 6,1) meses post inicio TDA.Dieciséis pacientes completaron docetaxel y 4 siguen en curso. No hubo suspensión de QMT por efectos adversos. Los más frecuentes fueron diarrea (8/20), neuropatía (5/20) y vómitos (2/20). La mayoría fue grado 1 y solo tres presentaron complicaciones grado 3 (diarrea, leucopenia y trombocitopenia). No hubo complicaciones grado 4 -5. Diez pacientes alcanzaron un antígeno < 2 ng/ml a las 12 semanas post tratamiento y 7 presentaron recidiva bioquímica durante el seguimiento. Uno tuvo respuesta imagenológica completa, 10 respuesta parcial, 7 estabilidad y 2 mostraron progresión. CONCLUSIONES: El uso de Docetaxel en mCSPC es seguro, presenta escasos efectos adversos (la mayoría de intensidad leve) que no motivan suspensión. El tratamiento con docetaxel exhibe una respuesta prometedora en términos de control de PSA, sin embargo se requiere mayor seguimiento de esta cohorte para evaluar impacto en sobrevida.(AU)

INTRODUCTION: Prostate cancer is a disease with high incidence and prevalence (90/100.000 habitants) and the second cause of cancer related death in men. Standard treatment in this setting is androgen-deprivation therapy (TDA), which causes decrease in PSA levels and stabilization or regression of metastatic lesions. Responses in castration sensitive phase last in average 3 years, after which tumor is described to become independent from the androgenic stimuli, reaching a castration-resistance (mCRPC) state. At this point chemotherapy with docetaxel as well as second line treatments (abiraterone, enzalutamide, among others)have shown to improve survival in 4 months with mean survival from diagnosis of mCRPC of 24 months. Studies including CHAARTED and STAMPEDE have demonstrated that early treatment with docetaxel with ADT in patients with mCSPC prolongs overall survival, especially if high volume disease exists. This study describes the clinical characteristics, initial oncologic response and side effects profile of mCSPC treated with Docetaxel plus ADT. MATERIALS AND METHODS: Descriptive Retrospective study from May 2014 to July 2017. mCSPC patients with high volume disease (extra axial bone metastasis, visceral metastasis or Gleason 9-10) and ECOG 0-1 were included. Patients received ADT and 6 cycles of Docetaxel. Demographic, clinical and histopathological characteristicswere registered, together with PSA, radiologic data (RECIST V1.1) and toxicity (NCI CAE 4.0). RESULTS: 20 patients were included, median age 63 years (49-75 range). Median initial PSA 267,5 ng/ml (10,8-5550 range), and median follow up 6 months (3-20 range). Fourteen patients had Gleason > 8, 18presented bone metastasis and 9/14 viscerametastasis. Only 1 patient received previous local treatment. Median initialtime to initiation of Docetaxel post ADT was 3,1 (0-6,1) months.Sixteen patients completed docetaxel and 4 are still receiving treatment. There was no chemotherapy suspension due side effects. Most frequent side effects were diarrhea (8/20), neuropathy (5/20) and vomiting (2/20). Most were grade 1 and three patients presented grade 3 side effects (diarrhea, leukopenia and thrombocytopenia). No grade 4-5 side effects were reported.Ten patients reached PSA< 2 ng/m after 12 weeks of treatment, and 7 had biochemical relapse during follow up. One had complete radiologic response, 10 partial response, 7 remained stable and 2 showed progression of disease. CONCLUSION: The use of docetaxel in mCSPC isassociated to few side effects and none requiredsuspension of treatment. Treatment with Docetaxel exhibits promising results in terms of decrease in PSA, however longer follow up and greater number of patients are required to report benefits in overall survival.(AU)

Serum testosterone level predicts the effective time of androgen deprivation therapy in metastatic prostate cancer patients / 亚洲男科学杂志(英文版)

Androgen deprivation therapy (ADT) is the standard of care for patients with metastatic prostate cancer. However, whether serum testosterone levels, using a cut-off point of 50 ng dl-1, are related to the effective time of ADT in newly diagnosed prostate cancer patients remains controversial. Moreover, recent studies have shown that some patients may benefit from the addition of upfront docetaxel chemotherapy. To date, no studies have been able to distinguish patients who will benefit from the combination of ADT and docetaxel chemotherapy. This study included 206 patients who were diagnosed with metastatic prostate cancer and showed progression to castrate-resistance prostate cancer (CRPC). Serum testosterone levels were measured prospectively after ADT for 1, 3, and 6 months. The endpoint was the time to CRPC. In univariate and multivariate analyses, testosterone levels <50 ng dl-1 were not associated with the effective time of ADT. Receiver operating characteristic and univariate analysis showed that testosterone levels of ≤25 ng dl-1 after the first month of ADT offered the best overall sensitivity and specificity for prediction of a longer time to CRPC (adjusted hazard ratio [HR], 1.46; 95% confidence interval [95% CI], 1.08-1.96; P = 0.013). Our results show that serum testosterone level of 25 ng dl-1 plays a prognostic role in prostate cancer patients receiving ADT. A testosterone value of 25 ng dl-1 after the first month of ADT can distinguish patients who benefit from ADT effectiveness for only a short time. These patients may need to receive ADT and concurrent docetaxel chemotherapy.

Predictors for progression of metastatic prostate cancer to castration-resistant prostate cancer in Indians.

Background & objectives: There is lack of data on natural history and progression of prostate cancer (PC) which have implications in the management of the disease. We undertook this retrospective study to analyze factors predicting progression of metastatic PC to castration-resistant prostate cancer (CRPC) in Indian men. Methods: Complete records of 223 of the 489 patients with metastatic PC were obtained from computerized data based system in a tertiary care hospital in north India between January 2000 to June 2012. Patients with follow up of < 6 months were excluded. Age (≤ and > 65 yr), baseline PSA (< and ≥ 50 ng/ml), bone scan and Gleason score (≤7 and >7) were recorded. Extent of bone disease (EOD) was stratified according to the number of bone lesions i.e., < 5, 5-10, > 10. CRPC was defined as two consecutive PSA rise of > 50 per cent from nadir or an absolute value of > 5 ng/ml. Results: Mean age of patients was 61.5 ± 12.45 yr and their PSA level was 325.6 ± 631.35 ng/dl. Of the 223 patients, 193 (86%) progressed to CRPC at median time of 10.7 (4-124) months. Median follow up was 24 (6-137) months. On univariate and multivariate analyses EOD on bone scan was found to be a significant predictor (P=0.006) for time to CRPC. Median time to CRPC was 10 months (CI 95%, 7.5-12.48) with >10 lesions or super scan versus 16 months (CI 95%, 10.3-21.6) with <10 bone lesion (P=0.01). Ninety (46.6 %) patients of CRPC died with median time to death from time of CRPC 21 (10-120) months. Interpretation & conclusions: Median time for progression of metastatic PC to CRPC ranged from 10-16 months depending on the extent of the bone involvement. In Indians, the aggressive course of advanced prostate cancer warrants further clinical trials to explore the need for additional treatment along with initial castration.

Evaluación de la efectividad de abiraterona en el tratamiento del cáncer de próstata metastásico / Evaluation of the effectiveness of abiraterone in treatment of metastatic prostate cáncer

Objetivo: estudiar el perfil de efectividad y seguridad de abiraterona en la práctica clínica, en pacientes con cáncer de próstata metastásico hormonoresistente. Métodos: se diseñó un estudio descriptivo retrospectivo de los pacientes diagnosticados con cáncer de próstata metastásico que recibieron tratamiento con abiraterona durante los mese de febrero 2012 a abril 2013. Las variables estudiadas fueron sexo, edad, escala del Eastern Cooperative Oncology Group (ECOG), tratamiento previo con docetaxel, antígeno prostático especifico (PSA) y supervivencia libre de progresión. La información se obtuvo de las historias clínicas, el programa de prescripción Savac® y el programa de validación farmacéutica Farmis‒Oncofarm®. Resultados: los 24 pacientes incluidos contaban una mediana de edad de 70 años. El estado funcional fue ECOG<2 en el 58,3 por ciento y ECOG≥2 en el 41,7 por ciento de los pacientes. El PSA disminuyó un 50 por ciento o más de su valor basal en el 52 por ciento de los pacientes. En cuanto a la supervivencia libre de progresión la mediana fue de 166 días (5,5 meses). En los pacientes con un ECOG≤2 la mediana fue de 231 días (7,7 meses) mientras que para los pacientes con ECOG˃2 fue de 106 días (3,5 meses). Abiraterona presentó pocas reacciones adversas por lo que resulta un fármaco seguro, a pesar de presentar algunas reacciones de suma importancia. Conclusiones: los resultados obtenidos en nuestra práctica clínica difieren con los obtenidos en los estudios pivotales. Se observan mayor supervivencia libre de progresión en los pacientes con un ECOG≤1 y en los que nunca habían recibido quimioterapia previa(AU)

Objectives: to study the efficacy and safety profile of abiraterone in clinical practice to treat patients with hormone-resistant metastatic prostate cancer. Methods: retrospective and descriptive study of patients who were diagnosed with metastatic prostate cancer and were treated with abiraterone since February 2012 to April 2013. The studied variables were gender, age, level of Eastern Cooperative Oncology Group (ECOG) scale, prior treatment with docetaxel, prostate specific antigen (PSA), progression-free survival (PFS). Data sources included medical records, the Savac® prescription and the Farmis-Oncofarm® pharmaceutical validation programs. Results: twenty-four patients were included, with average age of 70 years. The ECOG performance status was less than 2 in 58,3 percent of patients whereas 41,7 percent of the patients showed ECOG equal to 2 or higher. The PSA decreased by 50 percent or more its basal value in 52 percent of the patients. As regards to PFS, the median was 166 days (5,5 months) in progression-free survival. In patients with ECOG≤2, the median PFS was 231 days (7,7 months), whereas for patients with ECOG˃2,it was 106 days (3,5 months). Abiraterone has fewer side effects, so it may be considered a safe drug, although some are significant. Conclusions: the results obtained in our clinical practice differ from the ones obtained in the pivotal trials . Increased progression-free survival was observed in patients with an ECOG≤1 or less, and in those who had never received prior chemotherapy(AU)

Avaliação farmacoeconômica de diferentes apresentações de Eligard® e outros análogos LHRH para supressão androgênica em pacientes com câncer de próstata avançado ou metastático / Pharmacoeconomic evaluation of Eligard® and other LHRH analogues as androgen deprivation therapy for advanced and metastatic prostate cancer

Introdução: O acetato de leuprorrelina, substância ativa do medicamento Eligard®, é um análogo sintético não peptídeo do hormônio liberador do hormônio luteinizante (LHRH) que está bem estabelecido para o tratamento de primeira linha para pacientes com câncer de próstata avançado. Diversas opções de análogos LHRH estão disponíveis no Brasil, com diferentes formulações e periodicidade entre as aplicações. O Eligard® 45mg, de administração semestral, pode trazer vantagens clínicas e econômicas pela sua maior duração de efeito. Objetivo: Realizar uma avaliação econômica comparando diferentes apresentações de Eligard® e outros análogos LHRH no tratamento de pacientes com câncer de próstata avançado ou metastático no Brasil, sob as perspectivas do SUS, serviços públicos e saúde suplementar. Método: Modelos de Markov foram desenvolvidos para avaliar custos e desfechos em coortes de pacientes com câncer de próstata metastático, sem tratamento prévio, submetidos à terapia de privação androgênica e tratamentos subsequentes. Eligard® 45 mg, em sua forma de depósito semestral, foi colocado em perspectiva econômica com outras seis apresentações de análogos de LHRH disponíveis no mercado nacional. Resultados: O bloqueio androgênico, com qualquer um dos análogos LHRH avaliados, resultou em uma expectativa de vida média de 31,44 meses em todas as perspectivas analisadas...

Germline (CAG) n repeat length of androgen receptor among metastatic prostate cancer patients after endocrine therapy / 中华泌尿外科杂志

Objective To investigate the clinical significance of (CAG)n repeats length of androgen receptor (AR) among the patients with metastatic prostate cancer (TxNxM1),and to analyze their relevance to survival.Methods This study retrospectively investigated fifty-three metastatic prostate cancer patients aged 65 years (range 45-87) who were initially treated with endocrine therapy.The length of the (CAG) n repeats of blood samples was determined by both PCR sequencing and fragment analysis.The clinical significance of (CAG)n repeats and its correlation with biochemical progression free survival (bPFS)and overall survival (OS) were investigated.Results The median length of CAG repeats was 21,ranged from 14 to 32.According to the median (CAG)n repeats length,two groups were divided as (CAG)n ≤ 21and(CAG) n≥ 22.The median follow-up was 36 months.Patients with (CAG)n ≤ 21 had significantly shorter OS and bPFS than those with (CAG)n ≥ 22 (P ＜0.05).Shorter CAG repeats remained significant bPFS (HR 2.820,95％CI 1.466-5.427,P=0.002) and OS (HR 5.245,95％CI 1.293-21.27,P=0.020) predictor in multivariate analysis.Conclusions The efficacy of endocrine therapy for metastatic prostate cancer patients maybe influenced by the AR-CAG repeats length,and short (CAG) n repeats predict bad prognosis.

Body composition alterarions, energy expenditure and fat oxidation in elderly males suffering from prostate cancer, pre and post orchiectomy

INTRODUCTION: Testosterone is needed for normal male development, muscle strength, bone mineralization, hematopoietic function, and sexual and reproductive functions. The main purpose of androgen deprivation therapy in prostate cancer is to reduce tumor progression, but therapy is often accompanied by significant adverse effects. OBJECTIVE: This study aimed to determine the effects of androgen deprivation therapy on body composition and resting metabolic rate in patients with prostate cancer. PATIENTS AND METHODS: A prospective study was performed to evaluate the body composition of 16 elderly males (aged 63-96; median age 71) with prostate cancer scheduled for orchiectomy, one year before and after surgery. Body composition was measured by DEXA, and energy expenditure, fat and carbohydrate oxidation were measured by indirect calorimetry. RESULTS: Body weight (p=0.01), lean mass (p=0.004), and lipid oxidation (p=0.001) decreased significantly. Carbohydrate oxidation (p=0.02), FSH (p=0.0001) and LH (p=0.0001) levels increased significantly. Changes in fat mass (p=0.06) and bone mineral density (p=0.48) were not significant. CONCLUSIONS: After 12 months of androgen deprivation therapy, elderly men with metastatic prostate cancer exhibit a decline in lean body mass and lipid oxidation, together with increased carbohydrate oxidation.

Cancer of Unknown Primary Finally Revealed to Be a Metastatic Prostate Cancer: A Case Report / Journal of the Korean Cancer Association, 대한암학회지

The vast majority of patients with metastatic prostate cancer present with bone metastases and high prostate specific antigen (PSA) level. Rarely, prostate cancer can develop in patients with normal PSA level. Here, we report a patient who presented with a periureteral tumor of unknown primary site that was confirmed as prostate adenocarcinoma after three years with using specific immunohistochemical examination. A 64-year old man was admitted to our hospital with left flank pain associated with masses on the left pelvic cavity with left hydronephrosis. All tumor markers including CEA, CA19-9, and PSA were within the normal range. After an exploratory mass excision and left nephrectomy, the pelvic mass was diagnosed as poorly differentiated carcinoma without specific positive immunohistochemical markers. At that time, we treated him as having a cancer of unknown primary site. After approximately three years later, he revisited the hospital with a complaint of right shoulder pain. A right scapular mass was newly detected with a high serum PSA level (101.7 ng/ml). Tissues from the scapular mass and prostate revealed prostate cancer with positive immunoreactivity for P504S, a new prostate cancer-specific gene. The histological findings were the same as the previous pelvic mass; however, positive staining for PSA was observed only in the prostate mass. This case demonstrates a patient with prostate cancer and negative serological test and tissue staining that turned out to be positive during progression. We suggest the usefulness of newly developed immunohistochemical markers such as P504S to determine the specific primary site of metastatic poorly differentiated adenocarcinoma in men.