External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer

Purpose To assess outcomes with external beam radiation therapy (EBRT) and a low-dose-rate (LDR) brachytherapy boost without or with androgen deprivation therapy (ADT) for prostate cancer. Materials and Methods From January 2001 through August 2011, 120 intermediate-risk or high-risk prostate cancer patients were treated with EBRT to a total dose of 4,500 cGy in 25 daily fractions and a palladium-103 LDR brachytherapy boost of 10,000 cGy (n = 90) or an iodine-125 LDR brachytherapy boost of 11,000 cGy (n = 30). ADT, consisting of a gonadotropin-releasing hormone agonist ± an anti-androgen, was administered to 29/92 (32%) intermediate-risk patients for a median duration of 4 months and 26/28 (93%) high-risk patients for a median duration of 28 months. Results Median follow-up was 5.2 years (range, 1.1-12.8 years). There was no statistically-significant difference in biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), or overall survival (OS) without or with ADT. Also, there was no statistically-significant difference in bDFS, DMFS, or OS with a palladium-103 vs. an iodine-125 LDR brachytherapy boost. Conclusions There was no statistically-significant difference in outcomes with the addition of ADT, though the power of the current study was limited. The Radiation Therapy Oncology Group 0815 and 0924 phase III trials, which have accrual targets of more than 1,500 men, will help to clarify the role ADT in locally-advanced prostate cancer patients treated with EBRT and a brachytherapy boost. Palladium-103 and iodine-125 provide similar bDFS, DMFS, and OS. .

Tailored treatment including radical prostatectomy and radiation therapy + androgen deprivation therapy versus exclusive radical prostatectomy in high-risk prostate cancer patients: results from a prospective study

Purpose To evaluate outcomes of patients with high risk prostate cancer (PCa) who underwent radical prostatectomy (RP) in a context of a multidisciplinary approach including adjuvant radiation (RT) + androgen deprivation therapy (ADT). Matherials and Methods 244 consecutive patients with high risk localized PCa underwent RP and bilateral extended pelvic lymph node dissection at our institution. Adjuvant RT + 24 months ADT was carried out in subjects with pathological stage ≥ T3N0 and/or positive surgical margins or in patients with local relapse. Results After a median follow-up was 54.17 months (range 5.4-117.16), 13 (5.3%) subjects had biochemical progression, 21 (8.6%) had clinical progression, 7 (2.9%) died due to prostate cancer and 15 (6.1%) died due to other causes. 136 (55.7%) patients did not receive any adjuvant treatment while 108 (44.3%) received respectively adjuvant or salvage RT+ADT. Multivariate Cox proportional hazard analysis showed that pre-operative PSA value at diagnosis is a significant predictive factor for BCR (HR: 1.04, p < 0.05) and that Gleason Score 8-10 (HR: 2.4; p<0.05) and PSMs (HR: 2.01; p < 0.01) were significant predictors for clinical progression. Radical prostatectomy group was associated with BPFS, CPFS, CSS and OS at 5-years of 97%, 90%, 95% and 86% respectively, while adjuvant radiation + androgen deprivation therapy group was associated with a BPFS, CPFS and CSS at 5-years of 91%, 83%, 95% and 88%, without any statistical difference. Conclusions Multimodality tailored treatment based on RP and adjuvant therapy with RT+ADT achieve similar results in terms of OS after 5-years of follow-up. .

Impact of the National Health Fund policy on hormone treatment for prostate cancer in Jamaica / Repercusión de un subsidio del Fondo Nacional de Salud en la hormonoterapia para el cáncer de próstata en Jamaica

OBJECTIVE: To compare the proportion of patients choosing surgical versus medical castration to treat prostate cancer, before and after the National Health Fund (NHF) of Jamaica began to subsidize hormone therapy. METHODS: A retrospective review was performed at the University Hospital of the West Indies (UHWI), Jamaica. The pathology database at UHWI was searched to identify patients who had prostate biopsies between January 2000 and December 2007. These were combined with records of biopsies at external institutions. Medical records of all patients with positive prostate biopsies were reviewed to determine if they had received androgen deprivation therapy (ADT). Patients were classified as having had surgical castration (bilateral orchiectomy) or medical castration. Chi-square statistics were used to determine the difference in proportions between those choosing medical versus surgical castration before and after March 2005, when the NHF began offering subsidies for ADT drugs. RESULTS: Of the 1 529 prostate biopsies performed during the study period, 680 (44.0 percent) cases of prostate cancer were diagnosed. Of these, 458 patients underwent ADT and had complete records available for analysis. The mean patient age was 72 years. During the entire study period, surgical castration was performed in 265 patients (58.0 percent) and medical castration in 193 (42.0 percent). A greater proportion of orchiectomies were performed before March 2005, rather than after (P < 0.001). Estrogens were the most common method of medical castration used before the NHF subsidy became available (62.0 percent); while luteinizing hormone-releasing hormone analogues (38.0 percent) and antiandrogens (36.5 percent) were most often chosen afterwards. CONCLUSIONS: Surgical castration was more common than medical castration before March 2005. After the NHF began to subsidize the cost of drugs for hormone therapy, medical castration was chosen more often. Increased access to drugs for hormone therapy has changed treatment patterns in Jamaica.

OBJETIVO: Comparar la proporción de pacientes que eligen la castración quirúrgica frente a la castración farmacológica para tratar el cáncer de próstata, antes y después de la creación de un subsidio del Fondo Nacional de Salud (NHF, por sus siglas en inglés) de Jamaica destinado a cubrir los costos de la hormonoterapia. MÉTODOS: Se llevó a cabo un examen retrospectivo en el Hospital Universitario de las Indias Occidentales, Jamaica. Se efectuó una búsqueda en la base de datos de enfermedades de dicho hospital para identificar a los pacientes a quienes se les había practicado una biopsia de próstata entre enero del 2000 y diciembre del 2007. Los datos se combinaron con los registros de biopsias llevadas a cabo en instituciones externas. Se estudiaron las historias clínicas de todos los pacientes con resultados positivos en la biopsia de próstata para determinar si habían recibido tratamiento de supresión androgénica. Los pacientes se clasificaron en dos grupos, según se hubieran tratado mediante castración quirúrgica (orquiectomía bilateral) o farmacológica. Se usó la prueba de la ji al cuadrado para determinar la diferencia en las proporciones entre los pacientes que escogieron la castración quirúrgica y los que escogieron la opción farmacológica antes y después de marzo del 2005, la fecha en la que el NHF empezó a subsidiar los medicamentos de supresión androgénica. RESULTADOS: Entre las 1 529 biopsias de próstata realizadas durante el período de estudio, hubo 680 (44,0 por ciento) casos con diagnóstico de cáncer de próstata. De estos, 458 pacientes habían recibido tratamiento de supresión androgénica y se disponía de sus registros completos para el análisis. La edad media de los pacientes fue de 72 años. Durante el período de estudio, se les practicó castración quirúrgica a 265 pacientes (58,0 por ciento) y castración farmacológica a 193 (42,0 por ciento). La proporción de orquiectomías fue mayor antes de marzo del 2005 que después de esa fecha (P < 0,001). Los estrógenos fueron el método de castración farmacológica más común antes de la creación del subsidio del NHF (62,0 por ciento); a partir de ese momento se eligieron con mayor frecuencia los análogos de la hormona liberadora de la hormona luteinizante (38,0 por ciento) y los antiandrógenos (36,5 por ciento). CONCLUSIONES: La castración quirúrgica era más común que la castración farmacológica antes de marzo del 2005. Después de que el NHF empezó a subsidiar el costo de los medicamentos para el tratamiento hormonal, la opción escogida con más frecuencia fue la castración farmacológica. El mayor acceso a los medicamentos usados en la hormonoterapia ha cambiado los patrones de tratamiento del cáncer de próstata en Jamaica.

Risk factors for bone loss with prostate cancer in Korean men not receiving androgen deprivation therapy

PURPOSE: Preexisting bone loss in men with prostate cancer is an important issue due to the accelerated bone loss during androgen deprivation therapy (ADT). In addition, a high prostate-specific antigen (PSA) level has been reported to be related to bone metabolism. This study assessed the factors associated with osteoporosis in Korean men with non-metastatic prostate cancer before undergoing ADT. MATERIAL AND METHODS: The study enrolled patients admitted for a prostate biopsy because of a high PSA or palpable nodule on a digital rectal examination. We divided the patients (n = 172) according to the results of the biopsy: group I, non-metastatic prostate cancer (n = 42) and group II, benign prostatic hypertrophy (BPH; n = 130). The lumbar bone mineral density (BMD) was evaluated using quantitative computed tomography. The demographic, health status, lifestyle, body mass index (BMI), serum testosterone concentration, and disease variables in prostate cancer (Gleason score, clinical stage, and PSA) were analyzed prospectively to determine their effect on the BMD. RESULTS: The estimated mean T-score was higher in group I than in group II (-1.96 ± 3.35 vs. -2.66 ± 3.20), but without statistic significance (p = 0.235). The significant factors correlated with BMD in group I were a high serum PSA (ß = -0.346, p = 0.010) and low BMI (ß = 0.345, p = 0.014) in the multiple linear regression model. Also old age (r = -0.481, p = 0.001), a high serum PSA (r = -0.571, p < 0.001), low BMI (r = 0.598, p < 0.001), and a high Gleason's score (r = -0.319, p = 0.040) were the factors related to BMD in the correlation. The significant factors correlated with BMD in group II were old age (ß = -0.324, p = 0.001) and BMI (ß = 0.143, p = 0.014) in the multiple linear regression model. CONCLUSIONS: The risk factors for osteoporosis in men with prostate cancer include a low BMI, and elevated serum PSA. Monitoring BMD from the outset of ADT is a logical first...

Desdiferenciação do câncer da próstata após terapia antiandrogênica / Prostate cancer dedifferentiation following antiandrogen therapy: a morphological finding or an increased tumor aggressiveness?

OBJETIVO: O bloqueio androgênico neo-adjuvante em câncer da próstata produz involução do volume tumoral sem melhorar a evolução desses pacientes. Uma das explicações para esse fenômeno é a aquisição de comportamento mais agressivo pelas células tumorais remanescentes que, morfologicamente, apresentam aspecto mais indiferenciado após o bloqueio androgênico. Os objetivos do presente estudo foram avaliar a freqüência de desdiferenciação celular após tratamento antiandrogênico e definir se a neoplasia remanescente apresenta sinais de maior agressividade biológica. MÉTODOS: Trinta pacientes portadores de câncer da próstata localmente avançado foram submetidos a tratamento antiandrogênico neo-adjuvante por quatro meses, seguido de prostatectomia radical. Foram comparados os escores de Gleason da biópsia e do espécime cirúrgico. Ademais, mediu-se o índice de proliferação celular, determinado por imunohistoquímica para o PCNA, sendo considerados positivos os testes com reação nuclear intensa. A porcentagem de núcleos positivos, determinada em 500 células, foi confrontada com as diversas categorias do escore de Gleason do espécime cirúrgico. RESULTADOS: Em 11 espécimes cirúrgicos (37 por cento) o escore de Gleason foi igual ou menor que o encontrado na biópsia, enquanto em 19 (63 por cento) o escore cirúrgico foi maior que o da biópsia (p <0,05). A mediana de expressão do PCNA foi, respectivamente, de 4,5 por cento, 10 por cento, 12 por cento e 14 por cento para os escores de Gleason 2-4, 5-6, 7 e 8-10 (p> 0,05). A mediana dos índices de proliferação celular foi de 9 por cento para tumores confinados à glândula ou ao espécime e de 17 por cento para os extraprostáticos (p<0,05). CONCLUSÃO: Piora do escore de Gleason ocorreu em cerca de dois terços dos pacientes submetidos a tratamento hormonal anti-androgênico. Entretanto, os índices de proliferação celular, medidos pelo PCNA, foram iguais para espécimes com diferentes escores de Gleason. É provável que o bloqueio hormonal neo-adjuvante produza uma piora morfológica da neoplasia, sem, contudo, gerar clones celulares mais agressivos.