The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia

ABSTRACT Purpose We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. Materials and Methods We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. Results Among 195 (35.4%) patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001), Gleason score distribution (p<0.001), and number of positive biopsy cores (p<0.002) between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001). Moreover, increasing duration of metformin assumption (≥2 years) was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. Conclusions This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

Qualidade de vida relacionada à saúde de idosos em tratamento quimioterápico / Health-related quality of life of elderly people undergoing chemotherapy

OBJETIVO: Avaliar os efeitos da quimioterapia antineoplásica na qualidade de vida relacionada à saúde QVRS de idosos. MÉTODO: Foi analisada uma série de casos de idosos submetidos a quimioterapia antineoplásica, selecionados por amostra não probabilística do tipo tempo-local no período de agosto a dezembro de 2012. Foram incluídos idosos em tratamento quimioterápico e excluídos aqueles com indicação de radioterapia concomitante à quimioterapia. Para avaliação da QVRS, foi utilizado o European Organization for Research and Treatment of Cancer Quality of Life Questionnaire "core" 30 item EORTC-QLQ-C30, aplicado antes e cerca de dois meses após o início da quimioterapia. A qualidade de vida foi avaliada por meio da comparação das médias dos escores antes e depois da quimioterapia, por meio do teste t Student. RESULTADOS: Dos 31 pacientes observados, 58,1% eram do sexo feminino. As neoplasias mais frequentes foram: mama 32,3%, pulmão 22,6% e próstata 16,1%, sendo que 51,6% tinham o estadiamento clínico TNM IV. Para os 28 pacientes avaliados na segunda entrevista, o domínio "desempenho físico" teve variação da média "antes" e "depois" estatisticamente significante p=0,008, enquanto o domínio "estado de saúde geral/QV" teve média na primeira entrevista de 69,3 pontos e, após dois meses, 64,3 pontos sem diferença estatística p=0,413. Quando se analisou a QVRS por tipo de tumor, houve piora significativa nas médias dos escores no domínio "estado de saúde geral/QV" para os pacientes com neoplasia da próstata p=0,042. CONCLUSÃO: A quimioterapia piorou o desempenho físico sem modificar o estado geral de saúde de idosos, exceto para os pacientes com neoplasia da próstata.

OBJECTIVE: To evaluate cancer chemotherapy effects on health related quality of life HRQoL of elderly METHOD: A series of cases were analyzed on elderly undergoing anticancer chemotherapy selected by non-probability sample of the standard time-place from August to December 2012. The study included individuals undergoing chemotherapy and excluded those with indication for radiotherapy with chemotherapy. To evaluate HRQoL, we applied the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire "core" 30 item EORTC-QLQ-C30 before and two months after starting chemotherapy. The quality of life was assessed by comparing the mean scores before and after chemotherapy by Student t test. RESULTS: Of 31 patients observed, 58.1% were female. The most common cancer types were breast 32.3%, lung 22.6% and prostate 16.1%, and 51.6% were TNM IV classification. Of the 28 patients evaluated in the second interview, the domain "physical functioning" mean was statistically significant between "before" and "after" p=0.008 when evaluated all patients, while the domain "global health status/QoL" mean was 69.3 points in the first interview and 64.3 points after two months, with no statistical difference p=0.413. When assessed by type of cancer, there was a worsening in mean scores in the domain "global health status/QoL", in patients with prostate cancer p=0.042. CONCLUSION: Cancer chemotherapy worsened physical functioning without modifying the overall health status of the elderly, except for patients with prostate cancer.

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. .

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...

Evaluation of core and surface body temperatures, prevalence, onset, duration and severity of hot flashes in men after bilateral orchidectomy for prostate cancer

OBJECTIVE: To assess the prevalence, onset, duration and severity of hot flashes in men after bilateral orchidectomies (BO) for prostate cancer, to evaluate body temperature changes during hot flashes and to determine whether an elevated temperature within a few days after BO can be caused by deprivation of androgen. MATERIALS AND METHODS: Patients (n = 101) were questioned about the characteristics of their hot flashes after BO for prostate cancer. A subgroup of these men (n = 17) were instructed to record their oral and forehead temperatures during and at fixed intervals between hot flashes daily for 4 weeks. RESULTS: The mean age was 71.6 years, mean follow-up after BO was 33.2 months. Hot flashes were reported by 87 men (86 percent) with previous spontaneous remission in 9 (10 percent). The median time between BO and the onset of hot flashes was 21 days (range 1-730), median number of hot flashes 3 per day (range 1-20), and median duration was 120 seconds (range 5 to 1800). There was no significant difference between median oral (36.4º C) and forehead (36.0º C) temperature in the normal state, but during hot flashes the median forehead temperature (37.0º C) was higher than the oral temperature (36.5º C) (p = 0.0004). Both median oral and forehead temperatures were higher during hot flashes (36.5º C and 37.0º C) than in the normal state (36.4º C and 36.0º C, respectively) (p < 0.0001). During hot flashes, the oral temperature was 38º C to 40º C in only 3.2 percent of 593 readings in 17 patients. CONCLUSIONS: The median oral and forehead temperatures are higher during hot flashes than in normal periods. Oral temperature elevation > 38º C within days after a BO is unlikely to be the result of androgen deprivation alone.

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.

Biochemical failure as single abnormality in patients with prostate cancer following radical treatment with external radiotherapy: follow-up without immediate treatment

INTRODUCTION: Biochemical failure has been defined as 3 consecutive increases in PSA following curative treatment of prostate cancer. The appropriate management in such cases is controversial. The most usual treatment has been early introduction of hormones. Such patients will live for many years and hormone therapy causes important secondary effects and increases costs. The guideline in our Department of Radiotherapy has been to follow up, with no initial therapy, cases with low PSA and short PSA doubling time. The present study reports this experience. MATERIALS AND METHODS: 528 patients with localized prostate cancer were treated by radical approach between 1992 and 1999, with external radiotherapy, with or without adjuvant hormone therapy. After a median follow-up of 77 months, there were 207 (39 percent) cases with biochemical failure, 78 of which were followed without therapy after the identification of biochemical failure. All of them were asymptomatic patients and had negative radiographic examinations or did not have imaging exams requested since they presented a favorable outcome. The follow-up included at least 2 annual visits with physical examination and PSA. RESULTS: Of the 78 patients with biochemical failure followed without initial therapy, 7 died from other causes than prostate cancer and the remaining 71 cases were alive and asymptomatic in the last follow-up. Prognostic factors previous to radiotherapy such as stage and Gleason score were not considered when deciding for follow-up without initial therapy in these cases. The most significant aspects considered for this decision were low PSA value (median PSA on the last visit for the 78 cases was only 3.9 ng/mL) and a slow PSA doubling time (in the present experience the median PSA doubling time was 22.5 months). CONCLUSION: There seems to be space for expectant management, without initial hormone therapy, in patients with prostate cancer who present biochemical failure and are asymptomatic after radical external radiotherapy. This decision is important, since early introduction of hormones brings late effects and is expensive. Prospective and randomized studies are required to define this issue.