RESUMO
BACKGROUND: Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. INTERPRETATION: Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Assuntos
Antagonistas de Androgênios , Anilidas , Nitrilas , Prostatectomia , Neoplasias da Próstata , Compostos de Tosil , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Androgênios/administração & dosagem , Idoso , Compostos de Tosil/uso terapêutico , Compostos de Tosil/administração & dosagem , Anilidas/uso terapêutico , Anilidas/administração & dosagem , Pessoa de Meia-Idade , Nitrilas/uso terapêutico , Nitrilas/administração & dosagem , Oligopeptídeos/uso terapêutico , Oligopeptídeos/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Terapia Combinada , Antígeno Prostático Específico/sangueRESUMO
BACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. INTERPRETATION: Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Assuntos
Antagonistas de Androgênios , Anilidas , Nitrilas , Prostatectomia , Neoplasias da Próstata , Compostos de Tosil , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/cirurgia , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Androgênios/administração & dosagem , Idoso , Compostos de Tosil/uso terapêutico , Compostos de Tosil/administração & dosagem , Pessoa de Meia-Idade , Anilidas/uso terapêutico , Anilidas/administração & dosagem , Nitrilas/uso terapêutico , Nitrilas/administração & dosagem , Oligopeptídeos/administração & dosagem , Oligopeptídeos/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Antígeno Prostático Específico/sangue , Terapia Combinada , Esquema de MedicaçãoRESUMO
BACKGROUND: The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. METHODS: We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). INTERPRETATION: These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. FUNDING: Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.
Assuntos
Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Radioterapia Adjuvante , Terapia de Salvação , Análise de Sobrevida , Fatores de TempoRESUMO
PURPOSE: Emerging data indicate comparable disease control and toxicity of normal postoperative fractionation and moderate hypofractionation radiation therapy (RT) in prostate cancer. In RADICALS-RT, patients were planned for treatment with either 66 Gy in 33 fractions (f) over 6.5 weeks or 52.5 Gy in 20f over 4 weeks. This non-randomized, exploratory analysis explored the toxicity of these 2 schedules in patients who had adjuvant RT. METHODS AND MATERIALS: Information on RT dose was collected in all patients. The Radiation Therapy Oncology Group toxicity score was recorded every 4 months for 2 years, every 6 months until 5 years, then annually until 15 years. Patient-reported data were collected at baseline and at 1, 5, and 10 years using standard measures, including the Vaizey fecal incontinence score (bowel) and the International Continence Society Male Short-Form questionnaire (urinary incontinence). The highest event grade was recorded within the first 2 years and beyond 2 years and compared between treatment groups using the χ² test. RESULTS: Of 634 patients, 217 (34%) were planned for 52.5 Gy/20f and 417 (66%) for 66 Gy/33f. In the first 2 years, grade 1 to 2 cystitis was reported more frequently among the 66 Gy/33f group (52.5 Gy/20f: 20% vs 66 Gy/33f: 30%; P = .04). After 2 years, grade 1 to 2 cystitis was reported in 16% in the 66-Gy group and 9% in the 52.5-Gy group (P = .08). Other toxic effects were similar in the 2 groups, and very few patients had any grade 3 to 4 toxic effects. Patients reported slightly higher urinary and fecal incontinence scores at 1 year than at baseline, but no clinically meaningful differences were reported between the 52.5 Gy/20f and 66 Gy/33f groups. Patient-reported health was similar at baseline and at 1 year and similar between the 52.5 Gy/20f and 66 Gy/33f groups. CONCLUSIONS: Severe toxic effects were rare after prostate bed radiation therapy with either 52.5 Gy/20f or 66 Gy/33f. Only modest differences were recorded in toxic effects or in patient-reported outcomes between these 2 schedules.
Assuntos
Cistite , Incontinência Fecal , Neoplasias da Próstata , Humanos , Masculino , Próstata , Incontinência Fecal/etiologia , Fracionamento da Dose de Radiação , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Prostatectomia , Cistite/etiologia , Terapia de Salvação/efeitos adversos , Terapia de Salvação/métodosRESUMO
With the increasing prevalence of prostate cancer and evolving methods for the definitive treatment of OCPCa, health economic analyses will be critically important, albeit difficult to carry out. Preliminary studies point to RPP as the most cost-effective treatment for OCPCa. The quickest postoperative recovery, in experienced hands, occurs in RARP and RPP, with ORPP having a slightly, but statistically in significant, shorter hospital stay. It should be stressed that initial treatment costs are not the only important factor in healthcare costs. Readmission for early and late complications and the loss of productivity resulting from variation in time to return to work, need also to be considered. Loss of productivity may also vary in cost between different institutions and countries depending upon the proportion of patients employed. Further large-scale multicentre studies are necessary to assess this.
Assuntos
Crioterapia/economia , Prostatectomia/economia , Neoplasias da Próstata/terapia , Radioterapia/economia , Análise Custo-Benefício , Humanos , Masculino , Neoplasias da Próstata/economiaRESUMO
OBJECTIVE: To investigate the effects of weight loss and time post laparoscopic gastric banding surgery (LGB) on urinary and sexual function. MATERIALS AND METHODS: 653 females and 145 males who underwent LGB over the last 10 years at a single centre in Australia were contacted by post and asked to complete validated questionnaires. RESULTS: The pre-surgery body-mass index (BMI) was higher in males than females (47.3 vs 43.5); 65% of the females and 24% of males previously had some degree of urinary incontinence (UI). There were significant weight and BMI losses in males and females (23.2 kg and 7.51 vs 22.7 kg and 8.28; P < 0.0001). In females there were significant improvements in the ICIQ-SF (P= 0.0008) and Quality of Life (P < 0.0001) scores. For each kilogram lost there was a 0.05 improvement in the ICIQ score (P= 0.03) in females. There were also postoperative improvements in all symptoms of UI and stress incontinence in females but urge incontinence worsened, when adjusted for weight loss. In males there was no improvement in UI with weight loss after LGB. There was no relationship with time and UI in either gender; 83.3% of males reported a degree of ED before LGB. There was improvement in the IIEF score in males post LGB but there was worsening of erectile index (P= 0.005) and orgasmic function (P= 0.002) when adjusted for time. More males had started using phosphodiesterase type 5 inhibitors, post-LGB. CONCLUSIONS: Surgically induced weight loss by LGB improved overall UI, quality of life and stress incontinence in females but urge incontinence worsened. There was no improvement in UI with weight-loss or overall sexual function after LGB in males. However, erectile index and orgasmic function worsened when adjusted for time. Further evaluation is required by means of larger prospective studies involving urodynamic testing.
Assuntos
Gastroplastia/efeitos adversos , Obesidade Mórbida/cirurgia , Disfunções Sexuais Fisiológicas/etiologia , Incontinência Urinária/etiologia , Índice de Massa Corporal , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Resultado do Tratamento , Redução de PesoRESUMO
OBJECTIVE: To assess, in a retrospective three-centre series, a second analysis of the initial experience and results of patients undergoing radical cystectomy (RC) and orthotopic neobladder reconstruction (ONR) after an additional 4 years of follow-up. PATIENTS AND METHODS: The medical records of 104 suitable consecutive patients undergoing RC and ONR between June 1994 and April 2003 were reviewed retrospectively. The complications, mortality, continence and cancer control rates were all recorded. RESULTS: The median (range) follow-up was 88 (52-156) months; 90 patients had reconstruction with a 'Studer' neobladder, 12 with a Hautmann W pouch and 2 with a 'T pouch' ileal neobladder. There were 24 early complications, and one death after surgery. There were 32 late complications. The daytime continence rate was 98% and the nocturnal continence rate was 76%. Ten patients required intermittent self-catheterization (ISC). In all, 30 patients had local and/or distant recurrences, all of whom died. Seven patients died from other causes. CONCLUSIONS: ONR provides excellent long-term continence rates and both acceptable complication and mortality rates. Suitable patients undergoing RC should be offered ONR.
Assuntos
Cistectomia/métodos , Complicações Pós-Operatórias/etiologia , Doenças da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Coletores de Urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistectomia/efeitos adversos , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do TratamentoRESUMO
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms that account for 0.2% of all GI neoplasms. We report a case of a 62-year-old male with a large esophageal GIST, and discuss the pathophysiology of the disease and the current management principles. This case is noteworthy because it documents a rare lesion in the esophagus that presents like other neoplastic diseases in this organ that usually carry a poor prognosis. An aggressive approach (e.g., more radical surgery, radiotherapy, and chemotherapy) might have been pondered based purely on the size of the lesion in this patient. It is important that primary care physicians and surgeons be aware of the possibility of the presence of this potentially curable lesion so as to avoid overtreatment.
Assuntos
Neoplasias Esofágicas/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/uso terapêutico , Antineoplásicos/uso terapêutico , Benzamidas , Quimioterapia Adjuvante , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Esofagoscopia , Esôfago/patologia , Esôfago/cirurgia , Gastrectomia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/efeitos dos fármacosRESUMO
BACKGROUND: Men with suspected prostate cancer usually undergo transrectal ultrasound (TRUS)-guided prostate biopsy. TRUS-guided biopsy can cause side effects and has relatively poor diagnostic accuracy. Multiparametric magnetic resonance imaging (mpMRI) used as a triage test might allow men to avoid unnecessary TRUS-guided biopsy and improve diagnostic accuracy. OBJECTIVES: To (1) assess the ability of mpMRI to identify men who can safely avoid unnecessary biopsy, (2) assess the ability of the mpMRI-based pathway to improve the rate of detection of clinically significant (CS) cancer compared with TRUS-guided biopsy and (3) estimate the cost-effectiveness of a mpMRI-based diagnostic pathway. DESIGN: A validating paired-cohort study and an economic evaluation using a decision-analytic model. SETTING: Eleven NHS hospitals in England. PARTICIPANTS: Men at risk of prostate cancer undergoing a first prostate biopsy. INTERVENTIONS: Participants underwent three tests: (1) mpMRI (the index test), (2) TRUS-guided biopsy (the current standard) and (3) template prostate mapping (TPM) biopsy (the reference test). MAIN OUTCOME MEASURES: Diagnostic accuracy of mpMRI, TRUS-guided biopsy and TPM-biopsy measured by sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using primary and secondary definitions of CS cancer. The percentage of negative magnetic resonance imaging (MRI) scans was used to identify men who might be able to avoid biopsy. RESULTS: Diagnostic study - a total of 740 men were registered and 576 underwent all three tests. According to TPM-biopsy, the prevalence of any cancer was 71% [95% confidence interval (CI) 67% to 75%]. The prevalence of CS cancer according to the primary definition (a Gleason score of ≥ 4 + 3 and/or cancer core length of ≥ 6 mm) was 40% (95% CI 36% to 44%). For CS cancer, TRUS-guided biopsy showed a sensitivity of 48% (95% CI 42% to 55%), specificity of 96% (95% CI 94% to 98%), PPV of 90% (95% CI 83% to 94%) and NPV of 74% (95% CI 69% to 78%). The sensitivity of mpMRI was 93% (95% CI 88% to 96%), specificity was 41% (95% CI 36% to 46%), PPV was 51% (95% CI 46% to 56%) and NPV was 89% (95% CI 83% to 94%). A negative mpMRI scan was recorded for 158 men (27%). Of these, 17 were found to have CS cancer on TPM-biopsy. Economic evaluation - the most cost-effective strategy involved testing all men with mpMRI, followed by MRI-guided TRUS-guided biopsy in those patients with suspected CS cancer, followed by rebiopsy if CS cancer was not detected. This strategy is cost-effective at the TRUS-guided biopsy definition 2 (any Gleason pattern of ≥ 4 and/or cancer core length of ≥ 4 mm), mpMRI definition 2 (lesion volume of ≥ 0.2 ml and/or Gleason score of ≥ 3 + 4) and cut-off point 2 (likely to be benign) and detects 95% (95% CI 92% to 98%) of CS cancers. The main drivers of cost-effectiveness were the unit costs of tests, the improvement in sensitivity of MRI-guided TRUS-guided biopsy compared with blind TRUS-guided biopsy and the longer-term costs and outcomes of men with cancer. LIMITATIONS: The PROstate Magnetic resonance Imaging Study (PROMIS) was carried out in a selected group and excluded men with a prostate volume of > 100 ml, who are less likely to have cancer. The limitations in the economic modelling arise from the limited evidence on the long-term outcomes of men with prostate cancer and on the sensitivity of MRI-targeted repeat biopsy. CONCLUSIONS: Incorporating mpMRI into the diagnostic pathway as an initial test prior to prostate biopsy may (1) reduce the proportion of men having unnecessary biopsies, (2) improve the detection of CS prostate cancer and (3) increase the cost-effectiveness of the prostate cancer diagnostic and therapeutic pathway. The PROMIS data set will be used for future research; this is likely to include modelling prognostic factors for CS cancer, optimising MRI scan sequencing and biomarker or translational research analyses using the blood and urine samples collected. Better-quality evidence on long-term outcomes in prostate cancer under the various management strategies is required to better assess cost-effectiveness. The value-of-information analysis should be developed further to assess new research to commission. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16082556 and NCT01292291. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 39. See the NIHR Journals Library website for further project information. This project was also supported and partially funded by the NIHR Biomedical Research Centre at University College London (UCL) Hospitals NHS Foundation Trust and UCL and by The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research Biomedical Research Centre and was co-ordinated by the Medical Research Council's Clinical Trials Unit at UCL (grant code MC_UU_12023/28). It was sponsored by UCL. Funding for the additional collection of blood and urine samples for translational research was provided by Prostate Cancer UK.
Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/economia , Imageamento por Ressonância Magnética/economia , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Estudos de Coortes , Análise Custo-Benefício , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/normas , Humanos , Imageamento por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Anos de Vida Ajustados por Qualidade de Vida , Grupos Raciais , Sensibilidade e Especificidade , Medicina Estatal , Reino UnidoRESUMO
The current treatment for muscle invasive bladder cancer is radical cystectomy. However, this approach leads to significant changes in the patient's quality of life, as well as potential treatment failure. And so, with the introduction of alternative and neoadjuvant therapies available, the presence of pT0 tumour at cystectomy confers a number of issues. The variability in numbers of pT0 tumours at cystectomy highlights the importance of adequate clinical staging, as well as the increasing successful use of neoadjuvant chemotherapy. Although current literature is limited, patients with prior clinical stage of muscle-invasive but node-negative disease are likely to demonstrate the most improvement in survivability if they subsequently develop pT0 at cystectomy. This review also highlights the importance of response to chemotherapy as an indicator of subsequent prognosis. With increasing numbers of pT0 tumours seen at radical cystectomy, it is suggested that more conservative measures, such as re-staging following neoadjuvant chemotherapy and even 'selective bladder preservation' treatment, may be the future for the management of muscle invasive bladder cancer.
Assuntos
Cistectomia/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Terapia Neoadjuvante , Invasividade Neoplásica , Estadiamento de Neoplasias/métodos , Prognóstico , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
OBJECTIVES: To assess the influence of epigallocatechin-3-gallate (EGCG) on the efficacy of ionizing radiation on prostate cancer cells because of the increased use of dietary interventions, especially by patients with prostate cancer. Radiotherapy is used to treat localized prostate cancer. Some people consume green tea (EGCG) as a chemopreventive agent against prostate cancer. Green tea can act as an antioxidant and induce superoxide dismutase enzymes, which could scavenge the free oxygen radicals generated by radiotherapy. METHODS: Prostate cancer cell line DU145 cells were treated with EGCG or radiotherapy, or both. Cell death was assessed using trypan blue cell counting, and apoptosis was confirmed by assessing poly (adenosine phosphate ribose) polymerase cleavage. The antioxidant potential was assessed using Western immunoblotting for manganese superoxide dismutase and copper zinc superoxide dismutase enzymes. Radiotherapy was delivered using a linear accelerator. Cell cycle analysis was performed using flow cytometry. RESULTS: Radiotherapy at 3.5 Gy induced a 5.9-fold increase in apoptosis of DU145 cells. Subapoptotic doses of EGCG (1.5-7.5 µM) significantly reduced ionizing radiation-induced apoptosis (P < .001), with the inhibitory effect of EGCG on ionizing radiation being most effective when added 30 minutes before radiotherapy (P < .001). In addition, when radiotherapy and EGCG were used together, an approximate 1.5-fold increase in manganese superoxide dismutase levels was seen compared with the control and a 2-fold increase compared with radiotherapy alone. CONCLUSIONS: Radiotherapy is effective in inducing apoptosis in DU145 cells, but its effect was significantly reduced in the presence of EGCG, and this was associated with an increase in the induction of manganese superoxide dismutase.
Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Extratos Vegetais/farmacologia , Neoplasias da Próstata/radioterapia , Catequina/farmacologia , Humanos , Masculino , Neoplasias da Próstata/patologia , Chá , Resultado do Tratamento , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/efeitos da radiaçãoRESUMO
OBJECTIVE: To assess, in a retrospective three-centre series, the initial experience and results of patients undergoing radical cystectomy and orthotopic neobladder reconstruction. PATIENTS AND METHODS: The medical records were retrospectively reviewed for 104 suitable consecutive patients undergoing radical cystectomy and orthotopic neobladder reconstruction between June 1994 and April 2003. The initial histology, operating times, transfusion rates, complications, mortality rates, continence rates, potency rates, and cancer control rates were recorded. RESULTS: The median (range) follow-up was 48 (6-113) months; 90 patients had a reconstruction with a 'Studer' neobladder, 12 with a 'Hautmann W pouch' and two with a 'T pouch' ileal neobladder. There were 24 early complications, and in eight patients re-operation was required; there was one death after surgery. There were 14 late complications and 10 patients required re-operation. The daytime continence rate was 99% and the nocturnal continence rate 78%. Five patients required intermittent self-catheterization. Twenty-two patients died from local and/or distant recurrences, and four from other causes. CONCLUSIONS: Orthotopic neobladder reconstruction provides excellent continence rates, and both acceptable complication and mortality rates. Suitable patients undergoing radical cystectomy should be offered orthotopic neobladder reconstruction.
Assuntos
Cistectomia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Complicações Pós-Operatórias/etiologia , Recidiva , Estudos Retrospectivos , Coletores de UrinaRESUMO
Caspase-3 is a downstream effector cysteine protease in the apoptotic pathway. It is ubiquitously expressed in normal human tissues including the liver. Overexpression and loss of expression of caspase-3 has been reported in diverse human malignancies. However, expression of caspase-3 in hepatocellular carcinoma (HCC) has not been studied. Therefore, we studied its expression in four hepatoma cell lines and 22 HCCs by Western blot, and correlated the findings with in vitro caspase-3 activity and apoptosis. In addition, 47 surgically resected HCCs and 29 metastatic colorectal carcinomas were evaluated for caspase-3 expression by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections, and the staining intensity was correlated with the clinicopathological features. Caspase-3 overexpression was present in all four hepatoma cell lines, and 68% (15/22) of HCCs in comparison to the non-neoplastic liver parenchyma by Western blot, and in 52% (36/69) of HCCs by immunohistochemistry. Caspase-3 overexpression in HCCs by Western blot correlated with caspase-3 overexpression by immunohistochemistry (P=0.002), and in vitro caspase-3 activity (P=0.01). Caspase-3 overexpression in HCCs by immunohistochemistry was associated with serum alpha-fetoprotein (AFP) levels (P=0.01). In conclusion, caspase-3 is frequently overexpressed in HCCs and is associated with high serum levels of AFP.