RESUMEN
The aim of this retrospective study was to identify clinical predictors of early biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa) treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). A total of 670 high-risk PCa patients treated with CIRT and ADT were included in the study. Early BCR was defined as recurrence occurring during adjuvant ADT after CIRT or within 2 years after completion of ADT. Univariate and multivariate analyses were performed to identify clinical predictors of early BCR. Patients were also classified according to the Systemic Therapy in Advancing or Metastatic Prostate cancer (STAMPEDE) PCa classification. Early BCR was observed in 5.4% of the patients. Multivariate analysis identified clinical T3b stage and ≥75% positive biopsy cores as clinical predictors of early BCR after CIRT and ADT. The STAMPEDE PCa classification was also significantly associated with early BCR based on univariate analysis. These predictors can help clinicians identify patients who are at risk of early BCR. In the future, combination therapy of ADT with abiraterone may be an option for high-risk PCa patients who are at risk of early BCR, based on the results of the STAMPEDE study.
Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Antagonistas de Andrógenos/uso terapéutico , Andrógenos/uso terapéutico , Estudios Retrospectivos , Carbono/uso terapéuticoRESUMEN
Carbon-ion radiotherapy (CIRT) is a high-dose intensive treatment, whose safety and efficacy have been proven for prostate cancer. This study aims to evaluate the outcomes of CIRT in elderly patients with prostate cancer. Patients aged 75 years or above at the initiation of CIRT were designated as the elderly group, and younger than 75 years as the young group. The overall survival (OS), disease-specific survival (DSS), biochemical control rate (BCR), biochemical relapse-free survival (BRFS), and adverse events were compared between the elderly and young patients with high-risk prostate cancer treated with CIRT. The elderly group comprised 173 of 927 patients treated for high-risk prostate cancer between April 2000 and May 2018. The overall median age was 69 (range: 45−92) years. The median follow-up period was 91.9 (range: 12.6−232.3) months. The 10-year OS, DSS, BCR, and BRFS rates in the young and elderly groups were 86.9%/71.5%, 96.6%/96.8%, 76.8%/88.1%, and 68.6%/64.3%, respectively. The OS (p < 0.001) was longer in the younger group and the BCR was better in the elderly group (p = 0.008). The DSS and BRFS did not differ significantly between the two groups. The rates of adverse events between the two groups did not differ significantly and no patient had an adverse event of Grade 4 or higher during the study period. CIRT may be as effective and safe in elderly patients as the treatment for high-risk prostate cancer.
RESUMEN
The aim of this study was to reclassify high-risk prostate cancer patients treated with carbon-ion radiotherapy and androgen deprivation therapy using the Candiolo nomogram and evaluate usefulness to predict the following 10-year biochemical recurrence. Six hundred seventy-two high-risk prostate cancer patients were reclassified according to the Candiolo nomogram. The cumulative incidence curves for biochemical recurrence were compared by Gray's test. Furthermore, five predictors of the Candiolo nomogram in our patients were evaluated by Fine and Gray regression hazards model. The higher the Candiolo risk, the worse the biochemical recurrence, especially in high- and very high-risk patients. Out of five predictors, age ≥70 years, cT3 stage, biopsy Gleason score ≥9 or the percentage of positive biopsy cores ≥50% had significant impacts on 10-year biochemical recurrence in our patients. The Candiolo nomogram can reclassify our high-risk prostate cancer patients treated with carbon-ion radiotherapy and androgen deprivation therapy and evaluate the biochemical recurrence preciously.
Asunto(s)
Radioterapia de Iones Pesados , Neoplasias de la Próstata , Anciano , Antagonistas de Andrógenos/uso terapéutico , Andrógenos , Carbono , Supervivencia sin Enfermedad , Humanos , Masculino , Nomogramas , Antígeno Prostático Específico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Estudios RetrospectivosRESUMEN
BACKGROUND: We evaluated patient-reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca). METHODS: A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT-P questionnaires and EPIC urinary, bowel, and sexual bother subscales. RESULTS: The FACT-P total scores were significantly better (p < 0.05) in IADT versus CADT at 20 M (121.6 vs.115.4) and at 38 M (119.9 vs. 115.2). The physical well-being scores (PWB) were significantly better (p < 0.05) in IADT versus CADT at 38 M (25.4 vs. 24.0). The functional scores were significantly better in IADT than those in CADT at 14 M (20.2 vs18.7, p < 0.05) and at 20 M (21.0 vs.18.9, p < 0.05). CONCLUSION: The PRO was significantly favorable in IADT on FACT-P total score at 20 M and 38 M, PWB and functional scores at 38 M.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Anciano de 80 o más Años , Terapia Combinada/métodos , Humanos , Masculino , Terapia Neoadyuvante/métodos , Medición de Resultados Informados por el PacienteRESUMEN
BACKGROUND: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). METHODS: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. RESULTS: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). CONCLUSIONS: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.
Asunto(s)
Antagonistas de Andrógenos/administración & dosificación , Terapia Neoadyuvante/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Antagonistas de Andrógenos/efectos adversos , Terapia Combinada , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Modelos de Riesgos Proporcionales , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Radioterapia Conformacional/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: There is no consensus on blood adrenal androgen concentrations in men with different stages and pathological grades of prostate cancer. In this study, dehydroepiandrosterone (DHEA) concentrations in blood were examined by ultrasensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS). We analyzed the correlation between DHEA concentrations in blood and clinicopathological findings of prostate cancer. METHODS: We analyzed 196 men (mean age 70 years) with prostate cancer. The patients underwent systematic needle biopsy, and peripheral blood sampling was conducted for measurement of DHEA. DHEA concentrations in blood were determined using LC-MS/MS method. Patient age, serum prostate-specific antigen, prostate volume measured by ultrasound, and DHEA levels in blood were compared with Gleason score and clinical stage by multivariate analyses. RESULTS: Median value of PSA and prostate volume were 11.5 ng/ml and 27.7 ml, respectively. Median concentration of DHEA in blood was 1,506.4 pg/ml. There was no correlation between serum DHEA and clinical variables such as age, serum PSA, and prostate volume. In multivariate analysis, low serum DHEA levels in prostate cancer patients were significantly related to high Gleason score and advanced clinical stage. Serum PSA levels in prostate cancer patients were also significantly associated with high Gleason score and advanced clinical stage. High serum PSA and low serum DHEA levels were significantly associated with poor prognosis factors in men with hormone-naïve prostate cancer. CONCLUSIONS: DHEA concentrations in blood were examined by newly developed ultrasensitive LC-MS/MS. We confirmed that low serum DHEA levels in prostate cancer patients were related to high Gleason score and advanced clinical stage. These results suggest that serum DHEA level may be a useful prognostic factor in prostate cancer patients.
Asunto(s)
Cromatografía Liquida/métodos , Deshidroepiandrosterona/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Espectrometría de Masas en Tándem/métodos , Anciano , Biopsia con Aguja , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico por imagen , Espectrometría de Masa por Ionización de Electrospray/métodos , UltrasonografíaRESUMEN
BACKGROUND: There is currently no consensus on the correlations between androgen concentrations in prostate tissue and blood and stage and pathological grade of prostate cancer. In this study, we used a newly-developed ultra-sensitive liquid-chromatography tandem mass spectrometry method to measure testosterone (T) and dihydrotestosterone (DHT) concentrations in blood and needle biopsy prostate specimens from patients with prostate cancer. METHODS: We analyzed androgen levels in 196 men diagnosed with prostate cancer. All patients had undergone systematic needle biopsy, and an additional needle biopsy from the peripheral zone was conducted for the simultaneous determination of T and DHT. We analyzed the relationships between T and DHT levels in tissue and blood and Gleason score, clinical stage, and percentage of positive biopsy cores, using multivariate analysis. RESULTS: The median T and DHT levels in blood were 3551.0 pg/mL and 330.5 pg/mL, respectively. There was a strong correlation between serum T and DHT. The median T and DHT levels in prostate tissue were 0.5667 pg/mg and 7.0625 pg/mg, respectively. In multivariate analysis, serum prostate-specific antigen and tissue T levels were significantly associated with poor prognosis; high T levels in prostate tissue were significantly related to high Gleason score (p = 0.041), advanced clinical stage (p = 0.002), and a high percentage of positive biopsy cores (p = 0.001). CONCLUSIONS: The results of this study indicate that high T levels in prostate tissue are related to high Gleason score, advanced clinical stage, and a high percentage of positive biopsy cores in patients with prostate cancer. T level in needle biopsy specimens may therefore be a useful prognostic factor in prostate cancer patients.
Asunto(s)
Dihidrotestosterona/sangre , Calicreínas/sangre , Antígeno Prostático Específico/sangre , Próstata/metabolismo , Neoplasias de la Próstata/sangre , Testosterona/sangre , Anciano , Biopsia con Aguja , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Próstata/patología , Neoplasias de la Próstata/patologíaRESUMEN
BACKGROUND: A novel risk assessment method, Japan Cancer of the Prostate Risk Assessment, has been developed based on database of patients receiving primary androgen deprivation therapy. To investigate the usefulness of Japan Cancer of the Prostate Risk Assessment for non-metastatic, high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy. METHODS: Patients with non-metastatic, high-risk prostate cancer (T3, initial prostate specific antigen level ≥20 ng/ml, and/or Gleason score ≥8) were included. The patients were treated with carbon ion radiotherapy (the total dose from 57.6 Gy (relative biological effectiveness)/16 fractions to 66.0 Gy(relative biological effectiveness)/20 fractions), and neoadjuvant as well as adjuvant androgen deprivation therapy for at least 24 months. RESULTS: Four hundred and twenty-six patients were included with the median follow-up of 68.1 months. Of 426, 210 (49.3%), 270 (63.4%) and 251 (58.9%) had Gleason 8-10, prostate specific antigen ≥20 ng/ml and T3, respectively. The 10-year progression-free and cause-specific survival rates in Japan Cancer of the Prostate Risk Assessment 1-2 group (76.5 and 98.9%) were significantly better than those in Japan Cancer of the Prostate Risk Assessment 3-6 group (52.6 and 93.1%), (P < 0.001 and P = 0.044, respectively). The median progression-free survivals in the Japan Cancer of the Prostate Risk Assessment 1-2 and 3-6 groups were 158.9 months and 125.9 months (95% confidence interval: 108.6-143.2 months), respectively. CONCLUSIONS: For non-metastatic, high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy, Japan Cancer of the Prostate Risk Assessment score was useful for predicting the progression-free and cause-specific survivals.
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Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Biomarcadores de Tumor/sangre , Radioterapia de Iones Pesados , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Humanos , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Clasificación del Tumor , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Medición de Riesgo , Factores de RiesgoRESUMEN
We evaluated clinical outcomes of radical prostatectomy in 244 patients who had undergone radical prostatectomy as initial treatment from January 2000 to December 2011, and were followed up for more than 6 months. Biochemical recurrence after prostatectomy was defined as prostate-specific antigen (PSA) level of at least 0. 2 ng/ml. We evaluated potential risk factors for significant associations with biochemical recurrence. Median follow-up period after prostatectomy was 49 months (range, 6-144). Of the total, 192, 31, and 20 patients were at pathological stage pT2, pT3a, and pT3b, respectively. In 83 patients with the positive surgical margin, apexes were mostly in the positive area. Of the 68 patients with PSA recurrence, PSA non-relapse rate was 66.6% for 5 years. Multivariate analysis was performed for seminal vesicle invasion, PSA nadir, surgical margins, and Gleason score. Thirty-two patients with PSA recurrence underwent salvage radiotherapy, and the biochemical recurrence rate at 5 years was 73.8%. The group in which the PSA level before salvage radiotherapy was ï¼0.5 ng/ml had a low rate of biochemical recurrence. We must consider the recurrence of poorly differentiated or non-confined cancer after radical prostatectomy. These results suggest that early use of salvage radiotherapy is effective for patients with biochemical recurrence after radical prostatectomy.
Asunto(s)
Antígeno Prostático Específico/análisis , Prostatectomía , Neoplasias de la Próstata/cirugía , Anciano , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias de la Próstata/radioterapia , Estudios Retrospectivos , Terapia RecuperativaRESUMEN
BACKGROUND/AIM: Biochemical failure after radiotherapy for prostate cancer occurs infrequently, but some cases progress to a poor outcome. The aim of this study was to examine prognosis after biochemical failure. PATIENTS AND METHODS: A total of 728 patients were treated with carbon ion radiotherapy, and biochemical failure occurred in 90 (12.4%). Their outcomes were examined according to risk factors, histological findings, and androgen deprivation therapy (ADT). RESULTS: Biochemical failure rates were 12%, 6%, and 15% in low-, intermediate- and high-risk patients. Most patients responded favorably to salvage therapy. Some high-risk patients (25%) progressed to poor outcome; half experienced failure after ADT, while the rest during ADT, indicating that ADT had a slight influence. Patients who died from their disease had approximately two years of biochemical failure-free time and three years of survival after failure. Their tumor showed the presence and the increased proportion of histologically high-grade growth patterns. CONCLUSION: Histological growth patterns and short biochemical failure-free time are prognostic factors for poor outcome regardless of ADT.
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Neoplasias de la Próstata/radioterapia , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Radioisótopos de Carbono/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismoRESUMEN
BACKGROUND/AIM: Carbon ion radiotherapy is expected to be suitable to treat localized prostate cancer because it yields great biological and physical effects. The aim of this study was to examine long-term results and subsequent outcomes after biochemical failure. PATIENTS AND METHODS: A total of 254 patients were treated from the beginning of 2003 and followed through 2009. Long-term hormone therapy was also used for some intermediate-risk and high-risk patients. RESULTS: Among the patients examined, 54 patients experienced biochemical failure. Failure-free survival was 76%, 91% and 76% at eight years in low-risk, intermediate-risk and high-risk patients, respectively. Clinical progression occurred only in high-risk patients, with 89% progression-free survival at eight years. After biochemical failure, diseases of most patients were well controlled by salvage therapy but twelve high-risk patients (5%) died of prostate cancer. CONCLUSION: Carbon ion radiotherapy had an excellent effect on localized prostate cancer. Factors influencing salvage therapy included PSA kinetics and duration between radiation and failure.
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Adenocarcinoma/radioterapia , Radioterapia de Iones Pesados , Neoplasias de la Próstata/radioterapia , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Radioisótopos de Carbono/química , Radioisótopos de Carbono/uso terapéutico , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Factores de Riesgo , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
The incidence and clinical significance of the TMPRSS2:ERG gene fusion in prostate cancer has been investigated with contradictory results. It is now common knowledge that significant variability in gene alterations exists according to ethnic background in various kinds of cancer. In this study, we evaluated gene fusions involving the ETS gene family in Japanese prostate cancer. Total RNA from 194 formalin-fixed and paraffin-embedded prostate cancer samples obtained by radical prostatectomy was subjected to reverse-transcriptase polymerase chain reaction to detect the common TMPRSS2:ERG T1-E4 and T1-E5 fusion transcripts and five other non-TMPRSS2:ERG fusion transcripts. We identified 54 TMPRSS2:ERG-positive cases (54/194, 28%) and two HNRPA2B1:ETV1-positive cases (2/194, 1%). The SLC45A3-ELK4 transcript, a fusion transcript without structural gene rearrangement, was detectable in five cases (5/194, 3%). The frequencies of both TMPRSS2:ERG- and non-TMPRSS2:ERG-positive cases were lower than those reported for European, North American or Brazilian patients. Internodular heterogeneity of TMPRSS2:ERG was observed in 5 out of 11 multifocal cases (45%); a frequency similar to that found in European and North American cases. We found a positive correlation between the TMPRSS2:ERG fusion and a Gleason score of ≤7 and patient age, but found no relationship with pT stage or plasma prostate-specific antigen concentration. To exclude the possibility that Japanese prostate cancer displays novel TMPRSS2:ERG transcript variants or has unique 5' fusion partners for the ETS genes, we performed 5' RACE using fresh-frozen prostate cancer samples. We identified only the normal 5' cDNA ends for ERG, ETV1 and ETV5 in fusion-negative cases. Because we identified a relatively low frequency of TMPRSS2:ERG and other fusions, further evaluation is required before this promising molecular marker should be introduced into the management of Japanese prostate cancer patients.
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Fusión Génica , Prostatectomía , Neoplasias de la Próstata/genética , Proteínas Proto-Oncogénicas c-ets/genética , Anciano , Pueblo Asiatico/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Genotipo , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/genética , Humanos , Japón , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas de Fusión Oncogénica/genética , Adhesión en Parafina , Fenotipo , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Fijación del Tejido , Transactivadores/genética , Factores de Transcripción/genética , Regulador Transcripcional ERGRESUMEN
A 66-year-old man visited our hospital complaining of a high prostate-specific antigen (PSA) (6.9 ng/ml) and dysuria. Prostatic needle biopsies revealed no malignancy in January 1998 and February 1999 (PSA 8.0 ng/ml). Transurethral resection of prostate (TURP) was performed in March 1999. Although none of the TURP specimen showed any malignancy, the PSA level remained high (3.7 ng/ml 1 year after the TURP), and gradually increased. About 3 years later, re-biopsy was done (PSA 13.2 ng/ml) and pathological finding was moderately differentiated adenocarcinoma (Gleason score 3 + 3 = 6). After 9-month MAB, radical prostatectomy (RP) was performed in January 2003 (PSA 4.2 ng/ml). Though the RP specimen showed moderately differentiated adenocarcinoma with negative capsule penetration and negative surgical margins, PSA decreased to 2.5 ng/ml and gradually increased. Computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy showed neither distant metastasis nor local recurrence. Review of the RP specimen revealed ductal carcinoma with positive capsular penetration and suspicion of positive surgical margins. Although the patient was treated with maximum androgen blockade, diethylstilbestrol diphosphate, and tegafururacil, PSA gradually increased and was kept at a high level (5-6 ng/ml). In December 2005, the patient complained of anal pain and MRI showed a 4.8 x 2.3 cm tumor in the prostatic bed. Needle biopsy of the tumor revealed ductal carcinoma (PSA 6.39 ng/ml). In January 2006 (PSA 11.9 ng/ml), we initiated a treatment with 66 Gy of intensity modulated radiation therapy. In November 2006, PSA decreased to 0.279 ng/ml, and the tumor reduced (3.8 x 1.0 cm) on MRI.
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Adenocarcinoma/cirugía , Carcinoma Ductal/cirugía , Recurrencia Local de Neoplasia/etiología , Complicaciones Posoperatorias , Neoplasias de la Próstata/cirugía , Resección Transuretral de la Próstata , Adenocarcinoma/radioterapia , Anciano , Carcinoma Ductal/radioterapia , Terapia Combinada , Humanos , Masculino , Recurrencia Local de Neoplasia/radioterapia , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/radioterapia , Dosificación RadioterapéuticaRESUMEN
BACKGROUND: Radiation treatment for localized prostate cancer has become a prominent choice of monotherapy, and carbon ion beam is a powerful means for this purpose. METHODS: In total, 37 patients with localized prostate cancer were treated by monotherapy with carbon ion radiation and the outcome, more than 4 years later, was followed. RESULTS: PSA relapse-free survival was overall 85%, 5 years after radiation, and 96% in low-risk patients. Local control was mostly achieved, and no cancer-specific death was obtained. Except in cases of relapse, 1.0 ng/ml or less of PSA was shown in 78%, 3 years after radiation. Half of biopsy specimens out of 12 cases revealed non-viable or no cancer cells after a rather short time from treatment. CONCLUSION: Monotherapy with carbon ion radiation may be an excellent treatment for localized prostate cancer with low risk.
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Carbono/uso terapéutico , Neoplasias de la Próstata/radioterapia , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Dosis de Radiación , Medición de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
A major challenge for the management of prostate cancer (PCa) patients is to predict the clinical course of the disease after radical prostatectomy. A previous comprehensive immunohistochemical analysis using an automated image analyzer suggested that prolyl isomerase Pin1 (hence Pin1) may be a potent predictor of recurrence in PCa patients. However, a detailed pathological standard for evaluating the Pin1 immunohistochemistry in PCa has not been established yet. We here introduce a practical scoring system for Pin1 immunostaining in PCa. Using this method, the immunoreactivity of tumor cell cytoplasm and nucleus was evaluated separately and then scored for four grades (Grade=0-3). We defined the Pin1 score as the sum of both nuclear and cytoplasmic grades (Score=0-6), and the cases were then divided into either a low Pin1 score group (2) or a high Pin1 score group (3). We examined the correlation between this scoring system and postoperative PSA recurrence for 78 PCa patients. PCa patients assigned to the high Pin1 score group demonstrated PSA relapse more frequently than those assigned to the low Pin1 score group (p<0.0001). This suggests that, at the common laboratory level, our Pin1 scoring system could be a useful tool for predicting the prognosis of PCa patients after surgery.
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Carcinoma/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Isomerasa de Peptidilprolil/metabolismo , Prostatectomía , Neoplasias de la Próstata/metabolismo , Carcinoma/sangre , Carcinoma/patología , Supervivencia sin Enfermedad , Humanos , Inmunohistoquímica/métodos , Masculino , Peptidilprolil Isomerasa de Interacción con NIMA , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Isomerasa de Peptidilprolil/sangre , Valor Predictivo de las Pruebas , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patologíaRESUMEN
OBJECTIVE: To investigate patients with locally advanced prostate cancer treated at six academic institutions in eastern and north-eastern Japan from 1988 to 2000, to facilitate the establishment of Japanese guidelines for the diagnosis and treatment of locally advanced prostate cancer. PATIENTS AND METHODS: The study included 391 eligible patients with locally advanced prostate cancer who were treated by radical prostatectomy (RP), radiotherapy and/or primary hormone therapy. Disease-specific survival rates for these patients were assessed in relation to their clinicopathological characteristics and the types of treatment they received. The Mann-Whitney U-test, Kruskal-Wallis, chi-square and log-rank test were used for statistical analysis, as appropriate. RESULTS: In all, 128 patient with lower prostate-specific antigen levels (P = 0.023) and/or better performance status (P = 0.001) had RP. Neoadjuvant hormone therapy before RP was the treatment in 68 (53%) of these 128 patients; 66 (52%) received immediate adjuvant hormone therapy. Of 87 patients treated with radiotherapy, 75 (86%) had external beam radiotherapy (EBRT) as the primary treatment with no brachytherapy, and 12 (14%) had brachytherapy as the primary method. Neoadjuvant hormone therapy was given to 56 of the 87 patients (64%); 48 (55%) received immediate adjuvant hormone therapy. Of the 176 patients treated with primary hormone therapy alone, combined androgen blockade and surgical or medical castration was the treatment in 76 (43%) and 85 (48%), respectively. Disease-specific survival rates at 5 years for patients treated with RP, EBRT and primary hormone therapy were 90%, 98%, and 89%, respectively. CONCLUSION: The treatments provided by the participating institutions did not differ significantly from those set out in European and American guidelines, and short-term disease-specific survival rates for each treatment did not differ significantly from those of historical controls. Further investigation may facilitate the establishment of Japanese guidelines for the diagnosis and treatment of locally advanced prostate cancer.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Braquiterapia/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/terapia , Anciano , Anciano de 80 o más Años , Humanos , Japón , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Calidad de Vida , Estudios Retrospectivos , Factores de Riesgo , Estadísticas no Paramétricas , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy (EBRT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Between 2001 and 2003, 215 patients with locally advanced prostate cancer were enrolled in the study. Patients were registered as primary candidates of the study and were treated with 6 months of LHRH agonist, with short-term of antiandrogen treatment for flare-up prevention. Patients with PSA levels below 10 ng/ml after the 6-month endocrine treatment were randomly divided into two arms. Then, a total dose of 72 Gy was given to the prostate. After 14 months of the protocol treatment, patients were treated with continuous androgen ablation (arm 1) or intermittent androgen ablation (arm 2). RESULTS: A total of 188 cases (87%) remained in the protocol. The median PSA level at entry was 25.3 ng/ml. The Gleason score was 2-6 in 32 cases (16%), 7 in 94 cases (48%), and 8-10 in 68 cases (35%). The median PSA level showed a remarkable decrease to 1.1, 0.2, and 0.1 ng/ml, after 6, 8, and 14 months of the protocol treatment, respectively. Of the 157 cases treated with EBRT, 153 cases (97.5%) had no biochemical failure in the mean follow-up of 17.3 months. CONCLUSIONS: The present study may reveal the possibilities of intermittent endocrine therapy after EBRT. However, the follow-up interval is short and little can be said about the results observed so far, exception of acute tolerance and patient acceptance of the protocol.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Antineoplásicos Hormonales/administración & dosificación , Leuprolida/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Adenocarcinoma/mortalidad , Anciano , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/efectos adversos , Antineoplásicos Hormonales/efectos adversos , Braquiterapia , Acetato de Clormadinona/administración & dosificación , Acetato de Clormadinona/efectos adversos , Terapia Combinada , Supervivencia sin Enfermedad , Humanos , Leuprolida/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND: Heavy ion beams possess high linear energy transfer components and a prominent Bragg peak in the human body, resulting in higher relative biological effectiveness and improved dose distribution. To establish heavy ion therapy techniques for the treatment of prostate cancer, phase I/II clinical trials were initiated. METHODS: For 96 patients with T1b-T3 prostate cancer, three carbon ion beams were used to irradiate the prostate and seminal vesicles (20 times/5 weeks) with or without endocrine therapy. Radiation dose was expressed in GyE which was initially thought to be equivalent to photon dose. Total dose was gradually increased from 54 to 72 GyE. RESULTS: Carbon ion therapy was completed in 20 cases of T1b/T1c/T2aN0M0 as monotherapy, in 8 cases of T2b/T3pN0M0 with neoadjuvant endocrine therapy, and in 68 cases of T2b/T3N0/pN1M0 with neoadjuvant and adjuvant endocrine therapy. Median observation period was 47 months. Grade 3 late radiation morbidity of rectum and/or bladder/urethra developed in one and five cases who received 66 and 72 GyE of radiation, respectively. After these adverse effects were observed, total dose was decreased to 66 GyE and the radiation field was coned down during the treatment course. At 5 years, overall, cause-specific, clinical recurrence-free, and biochemical recurrence-free survival rates were 87.7, 94.9, 90.0, and 82.6%, respectively. Local control was achieved in all patients except one patient who received 54 GyE of radiation. CONCLUSIONS: The therapeutic techniques of carbon ion therapy have been established for patients with prostate cancer. Carbon ion therapy may exert excellent effect to the tissues of prostate cancer.