RESUMO
OBJECTIVES: To explore the effects of preoperative high-intensity interval training (HIIT) compared to usual care on tumour natural killer (NK)-cell infiltration in men with localised prostate cancer (PCa), as NK-cell infiltration has been proposed as one of the key mechanisms whereby exercise can modulate human tumours. PATIENTS AND METHODS: A total of 30 patients with localised PCa undergoing radical prostatectomy (RP) were randomised (2:1) to either preoperative aerobic HIIT four-times weekly (EX; n = 20) or usual care (CON; n = 10) from time of inclusion until scheduled surgery. Tumour NK-cell infiltration was assessed by immunohistochemistry (CD56+ ) in diagnostic core needle biopsies and corresponding prostatic tissue from the RP. Changes in cardiorespiratory fitness, body composition, blood biochemistry, and health-related quality of life were also evaluated. RESULTS: The change in tumour NK-cell infiltration did not differ between the EX and CON groups (between-group difference: -0.09 cells/mm2 , 95% confidence interval [CI] -1.85 to 1.66; P = 0.913) in the intention-to-treat analysis. The total number of exercise sessions varied considerably from four to 30 sessions. The per-protocol analysis showed a significant increase in tumour NK-cell infiltration of 1.60 cells/mm2 (95% CI 0.59 to 2.62; P = 0.004) in the EX group. Further, the total number of training sessions was positively correlated with the change in NK-cell infiltration (r = 0.526, P = 0.021), peak oxygen uptake (r = 0.514, P = 0.035) and peak power output (r = 0.506, P = 0.038). CONCLUSION: Preoperative HIIT did not result in between-group differences in tumour NK-cell infiltration. Per-protocol and exploratory analyses demonstrate an enhanced NK-cell infiltration in PCa. Future studies are needed to test the capability of exercise to increase tumour immune cell infiltration.
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Neoplasias da Próstata , Qualidade de Vida , Masculino , Humanos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Exercício Físico , Próstata/patologia , Células Matadoras NaturaisRESUMO
PURPOSE: To investigate differences in prescription rates of commonly used drugs among prostate cancer patients and cancer-free comparisons and between patients diagnosed with localized and non-localized disease. METHODS: We conducted a register-based study including all men aged 50-85 years diagnosed with prostate cancer in Denmark from 1998 to 2015 and an age-matched cancer-free comparison cohort. We calculated the number of new and total prescriptions from three years before to three years after the date of diagnosis of the case for selected drug classes divided by the number of person-months and stratified by stage at diagnosis. RESULTS: We included 54,286 prostate cancer patients and 249,645 matched comparisons. 30,712 patients were diagnosed with localized disease and 12,884 with non-localized disease. The rates of new prescriptions increased considerably among patients within the year before the diagnosis. Hereafter the rates varied between drug classes. For most drug classes, total prescription rates for patients and comparisons increased similarly in the study period. Total prescription rates varied between men with localized and non-localized disease for all drug classes apart from statins. CONCLUSION: Our findings indicate that a large proportion of prostate cancer cases are likely diagnosed during medical work-up for other reasons than prostate cancer. Increased rates occur within the last year before diagnosis and future studies on the interaction between drug use and prostate cancer should at least include a one year pre-diagnostic lag-time. Post-diagnostic prescription rates demonstrated an increased use of drugs most likely associated with the consequences of the disease.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Preparações Farmacêuticas , Neoplasias da Próstata , Idoso , Idoso de 80 Anos ou mais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prescrições , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/epidemiologiaRESUMO
PURPOSE: Magnetic resonance imaging (MRI) targeted prostate biopsy has been shown to find many high-grade prostate cancers in men with concurrent negative transrectal ultrasound (TRUS) systematic biopsy. The oncologic risk of such tumors can be explored by looking at long-term outcomes of men with negative TRUS biopsy followed without MRI. The aim was to analyze the mortality after initial and second negative TRUS biopsy. MATERIALS AND METHODS: All men who underwent initial TRUS biopsies between January 1, 1995 and December 31, 2016 in Denmark were included. A total of 37,214 men had a negative initial TRUS biopsy and 6,389 underwent a re-biopsy. Risk of cause-specific mortality was analyzed with competing risks. Diagnosis of Gleason score ≥7 prostate cancer following negative biopsies was analyzed with multivariable logistic regression including time to re-biopsy, prostate specific antigen (PSA), age and digital rectal examination. RESULTS: The 15-year prostate cancer-specific mortality was 1.9% (95% CI: 1.7-2.1). Prostate cancer-specific mortality was 1.3% (95% CI: 0.9-1.6) and 4.6% (95% CI: 3.4-5.8) for men with PSA <10 and >20 ng/ml, respectively. Of the TRUS re-biopsies 12% were Gleason score ≥7 and risk of Gleason score ≥7 increased with longer time to re-biopsy (p <0.001). Mortality after re-biopsy was similar to after initial biopsy. CONCLUSIONS: Men with negative TRUS biopsies have a very low prostate cancer-specific mortality, especially with PSA <10 ng/ml. This raises serious questions about the routine use of MRI targeting for initial prostate biopsy and suggests that MRI targeting should only be recommended for men with PSA >10 ng/ml after negative biopsy.
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Próstata , Neoplasias da Próstata , Biópsia , Seguimentos , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Gradação de Tumores , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologiaRESUMO
PURPOSE: This study aims to examine quality of life (QoL) before and after radical cystectomy (RC) and compare robot-assisted laparoscopy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). METHODS: This study is a predefined secondary analysis of a single-centre, double-blinded, randomised feasibility trial. Fifty patients were randomly assigned to iRARC with ileal conduit (n = 25) or ORC with ileal conduit (n = 25). Patients were followed 90 days postoperatively. The primary outcome was patient-reported QoL using the EORTC Cancer-30 and muscle-invasive bladder cancer BLM-30 QoL questionnaires before and after RC. Differences between randomisation arms as well as changes over time were evaluated. Secondary outcomes included 30- and 90 day complication rates, 90 day readmission rates, and 90 day days-alive-and-out-of-hospital and their relationship to QoL. RESULTS: All patients underwent the allocated treatment. We found no difference in QoL, complication rates, readmission rates, and days-alive-and-out-of-hospital between randomisation arms. An overall improvement in QoL was found in the following domains: future perspectives, emotional functioning, and social functioning. Sexual functioning worsened postoperatively. There was no association between having experienced a major complication or lengthy hospitalisation and worse postoperative QoL. CONCLUSION: The QoL does not appear to depend on surgical technique. Apart from sexual functioning, patients report stable or improved QoL within the first 90 postoperative days.
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Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Bexiga Urinária , Derivação Urinária , Cistectomia/métodos , Estudos de Viabilidade , Humanos , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/etiologia , Derivação Urinária/métodosRESUMO
OBJECTIVES: To evaluate the effects of center experience and a variety of patient- and procedure-related factors on patient radiation exposure during prostatic artery embolization (PAE) in three Scandinavian centers with different PAE protocols and levels of experience. Understanding factors that influence radiation exposure is crucial in effective patient selection and procedural planning. METHODS: Data were collected retrospectively for 352 consecutive PAE procedures from January 2015 to June 2020 at the three centers. Dose area product (DAP (Gy·cm2)) was selected as the primary outcome measure of radiation exposure. Multiple patient- and procedure-related explanatory variables were collected and correlated with the outcome variable. A multiple linear regression model was built to determine significant predictors of increased or decreased radiation exposure as reflected by DAP. RESULTS: There was considerable variation in DAP between the centers. Intended unilateral PAE (p = 0.03) and each 10 additional patients treated (p = 0.02) were significant predictors of decreased DAP. Conversely, increased patient body mass index (BMI, p < 0.001), fluoroscopy time (p < 0.001), and number of digital subtraction angiography (DSA) acquisitions (p < 0.001) were significant predictors of increased DAP. CONCLUSIONS: To minimize patient radiation exposure during PAE radiologists may, in collaboration with clinicians, consider unilateral embolization, pre-interventional CTA for procedure planning, using predominantly anteroposterior (AP) projections, and limiting the use of cone-beam CT (CBCT) and fluoroscopy. KEY POINTS: ⢠Growing center experience and intended unilateral embolization decrease patient radiation exposure during prostatic artery embolization. ⢠Patient BMI, fluoroscopy time, and number of DSA acquisitions are associated with increased DAP during procedures. ⢠Large variation in radiation exposure between the centers may reflect the use of CTA before and CBCT during the procedure.
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Embolização Terapêutica , Hiperplasia Prostática , Exposição à Radiação , Angiografia Digital/métodos , Artérias/diagnóstico por imagem , Embolização Terapêutica/métodos , Fluoroscopia , Humanos , Masculino , Próstata/irrigação sanguínea , Próstata/diagnóstico por imagem , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/terapia , Doses de Radiação , Estudos RetrospectivosRESUMO
BACKGROUND: Symptoms and treatment of benign prostatic hyperplasia (BPH) or erectile dysfunction (ED) may lead to prostate cancer workup, and patterns of prescriptions before diagnosis may affect findings of pharmacoepidemiological studies. Usage of BPH and ED drugs after diagnosis may be related to prostate cancer treatment. We investigated differences in prescription rates of BPH and ED drugs among prostate cancer patients and cancer-free comparisons and between patients with localized and non-localized disease. MATERIAL AND METHODS: A nationwide register-based study, including all Danish men aged 50-85 years diagnosed with prostate cancer during 1998-2015 and an age-matched comparison cohort without cancer. We calculated rates of new and total prescriptions in 1-month intervals from 3 years before to 3 years after cancer diagnosis for drugs used to treat BPH and ED, overall and stratified by clinical stage. RESULTS: We identified 54,286 men with prostate cancer and a comparison cohort of 249,645 age-matched men. The new prescription rate for BPH drugs increased for men with prostate cancer in the year before diagnosis and peaked 1 month before diagnosis with an 18-fold higher rate. Men with prostate cancer had a higher total prescription rate of BPH drugs 3 years before diagnosis, notably among men with localized disease. Before diagnosis, the new prescription rates for ED drugs were similar among men with prostate cancer and comparisons. After diagnosis, men with prostate cancer had a 7-fold higher rate of new prescriptions for ED drugs. Among men with localized disease, the total prescription rate of ED drugs increased in the months following diagnosis. CONCLUSION: Differences in prescription rates suggest increased prostate cancer surveillance among men receiving BPH drugs, whereas the post-diagnostic increase in ED drugs among men with localized disease is compatible with the increased risk of ED following prostate cancer treatment.
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Disfunção Erétil , Hiperplasia Prostática , Neoplasias da Próstata , Estudos de Coortes , Disfunção Erétil/diagnóstico , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/epidemiologia , Humanos , Masculino , Prescrições , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/tratamento farmacológico , Neoplasias da Próstata/complicações , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológicoRESUMO
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.
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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
OBJECTIVE: To compare the risk of depression after diagnostic workup for prostate cancer (PCa), regardless of the histopathologic outcome, with that of a cancer-free population. METHODS: A nationwide cohort of Danish men who had a prostatic biopsy sample in 1998-2011 was identified from the Danish Prostate Cancer Registry and compared to an age-matched cohort from the background population. Men with other cancers, major psychiatric disorder, or prior use of antidepressants were excluded. The risk of depression defined as hospital contact for depression or prescription for antidepressants was determined from cumulative incidence functions and multivariate Cox regression models. RESULTS: Of 54,766 men who underwent diagnostic workup for PCa, benign results were found for 21,418 and PCa was diagnosed in 33,347. During up to 18 years of follow-up, the adjusted hazard of depression was higher in men with PCa than in the background population, with the highest risk in the two years after diagnosis (hazard ratio (HR) 2.77, 95% CI 2.66-2.87). Comorbidity and lowest or highest income were significant risk factors for depression and the cumulative incidence was substantially higher in men with metastatic or high-risk disease. In men with benign histopathology the HR for depression was 1.22 (95% CI 1.14-1.31) in the first two years but no different from the background population after that. CONCLUSIONS: Diagnostic workup for PCa is associated with an increased risk of depression, mainly among men with a diagnosis of PCa. Clinicians should be aware of depressive symptoms in prostate cancer patients.
Assuntos
Depressão , Neoplasias da Próstata , Estudos de Coortes , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Humanos , Masculino , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Sistema de RegistrosRESUMO
BACKGROUND: The extent to which positive surgical margins (PSM) affect the risk of subsequent salvage radiation therapy (sRT) or androgen depletion therapy (ADT) following radical prostatectomy (RP) is not well described. Initiation of additional therapies after RP depend on patient preference, individual factors, local guidelines, and life expectancy. The aim of this study was to analyze differences between margin status in risk of subsequent treatment for PCa following RP in a retrospective population-based cohort from Denmark. METHODS: Patients who underwent RP were identified in The Danish Prostate Cancer Registry (DaPCaR). Subsequent sRT and ADT were assessed in uni- and multivariate settings and validated with receiver operating characteristic (ROC). RESULTS: PSM was associated with an increased risk of sRT (HR = 1.85, p < .001) and receiving ADT (HR:1.39, p = .007). Margin status only had a minor impact on the predictive ability for sRT (area under the curve (AUC): p < .001) and no significant impact for subsequent ADT (AUC: p = 1). Significant inter-institutional difference in the association between PSM with sRT or ADT was observed. CONCLUSION: PSM is associated with the risk of sRT and initiation of ADT, however this association is weak. Our results underline that factors beyond tumor characteristics play a major role for initiation of sRT and ADT.
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Antagonistas de Androgênios , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Masculino , Margens de Excisão , Recidiva Local de Neoplasia/epidemiologia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Terapia de SalvaçãoRESUMO
BACKGROUND: Vitamin D has a role in bone turnover and potentially bone-metastatic spread of prostate cancer (PCa). The aim of this observational study was to address the association between levels of serum vitamin D, diagnosis of PCa and subsequent mortality in men who underwent a biopsy of the prostate. METHODS: All men who underwent prostatic biopsy in the Danish PCa Registry (DaPCaR) and who had a serum vitamin D measurement during the period 2004 to 2010 (n = 4,065) were identified. Men were categorized by clinical cut-offs based on seasonally adjusted serum vitamin D levels in <25 (deficient), 25-50 (insufficient), 50-75 (sufficient) and >75 nmol/L (high) serum vitamin D. Logistic regression model for association between vitamin D and risk of PCa diagnosis and multivariate survival analyses were applied. RESULTS: No association between serum vitamin D and risk of PCa was found. Overall survival was lowest for serum vitamin D deficiency and a significantly higher PCa specific mortality (HR: 2.37, 95%CI: 1.45-3.90, p < .001) and other cause mortality (HR: 2.08, 95%CI: 1.33-3.24, p = .001) was found for PCa patients with serum vitamin D deficiency compared to serum vitamin D sufficiency. CONCLUSION: No association was found between serum vitamin D categories and risk of PCa in men who underwent biopsy of the prostate. Men with PCa and serum vitamin D deficiency had a higher overall and PCa specific mortality compared to men with a sufficient level of serum vitamin D.
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Neoplasias da Próstata , Vitamina D , Biópsia , Humanos , Modelos Logísticos , Masculino , Neoplasias da Próstata/epidemiologiaRESUMO
miR-615-3p has previously been described as up-regulated in prostate cancer (PC) tissue samples compared with nonmalignant controls; however, its prognostic potential and functional role in PC remain largely unknown. In this study, we investigated the clinical and biological relevance of miR-615-3p in PC. The expression of miR-615-3p was measured in PC tissue specimens from 239 men who underwent radical prostatectomy (RP), and it was investigated if miR-615-3p could predict postoperative biochemical recurrence (BCR). These findings were subsequently validated in three independent RP cohorts (n = 222, n = 273, and n = 387) and functional overexpression studies conducted in PC cells (PC3M). High miR-615-3p expression was significantly associated with BCR in four independent PC patient cohorts (P < 0.05, log-rank test). In addition, high miR-615-3p expression was a significant predictor of PC-specific survival in univariate (hazard ratio, 3.75; P < 0.001) and multivariate (hazard ratio, 2.66; P = 0.008) analysis after adjustment for the Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) nomogram in a merged RP cohort (n = 734). Moreover, overexpression of miR-615-3p in PC cells (PC3M) significantly increased cell viability, proliferation, apoptosis, and migration. Together, our results suggest that miR-615-3p is a significant predictor of postoperative BCR and PC-specific survival and has oncogenic functions in PC cells.
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Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , MicroRNAs/genética , Recidiva Local de Neoplasia/mortalidade , Prostatectomia/mortalidade , Neoplasias da Próstata/mortalidade , Adulto , Idoso , Estudos de Coortes , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
This study aimed to validate whether 5-hydroxymethylcytosine (5hmC) level in combination with ERG expression is a predictive biomarker for biochemical failure (BF) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa). The study included 592 PCa patients from two consecutive Danish RP cohorts. 5hmC level and ERG expression were analyzed using immunohistochemistry in RP specimens. 5hmC was scored as low or high and ERG was scored as negative or positive. Risk of BF was analyzed using stratified cumulative incidences and multiple cause-specific Cox regression using competing risk assessment. Median follow-up was 10 years (95% CI: 9.5â»10.2). In total, 246 patients (41.6%) had low and 346 patients (58.4%) had high 5hmC level. No significant association was found between 5hmC level or ERG expression and time to BF (p = 0.2 and p = 1.0, respectively). However, for men with ERG negative tumors, high 5hmC level was associated with increased risk of BF following RP (p = 0.01). In multiple cause-specific Cox regression analyses of ERG negative patients, high 5hmC expression was associated with time to BF (HR: 1.8; 95% CI: 1.2â»2.7; p = 0.003). In conclusion, high 5hmC level was correlated with time to BF in men with ERG negative PCa, which is in accordance with previous results.
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5-Metilcitosina/análogos & derivados , Prostatectomia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/cirurgia , 5-Metilcitosina/metabolismo , Idoso , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Curva ROC , Regulador Transcricional ERG/metabolismoRESUMO
OBJECTIVES: To elucidate the role of prostate-specific antigen (PSA) doubling time (PSAdt) as a progression criterion in patients with low-risk prostate cancer managed by active surveillance (AS). To assess the correlation between PSAdt during AS and final histopathology after radical prostatectomy (RP) in patients meeting predefined progression criteria. PATIENTS AND METHODS: A total of 258 consecutive patients on an AS programme were included in the study. The PSAdt was calculated in patients with two or more PSA values, and 95% confidence intervals (CIs) were calculated in patients with four or more PSA values. Progression risk groups were defined as follows: high-risk: PSAdt <3 years, rebiopsy Gleason score (GS) ≥4 + 3, more than three positive biopsy cores, and/or bilateral tumour or cT ≥2c disease; intermediate-risk: PSAdt 3-5 years, GS = 3 + 4 or cT2b disease; and low-risk: PSAdt >5 years, without histopathological or clinical progression. Definitive treatment was recommended for patients in the high-risk group and treatment options were discussed with those in the intermediate-risk group. RESULTS: A total of 2291 PSA values obtained during AS were available, of which 2071 were considered valid in the 258 patients. PSAdt values with 95% CIs were calculated in 221 patients based on a median of 8 PSA values. The 95% CIs for PSAdt overlapped considerably and in up to 91% of the patients, the 95% CIs overlapped among the risk group definitions. A total of 26% (68/258 patients) underwent RP after meeting the progression criteria. There was no association between preoperative PSAdt and final histopathology (P = 0.87). CONCLUSION: The uncertainty of calculated PSAdt during AS leads to a significant risk of patients being misclassified in terms of risk of progression, which limits the use of PSAdt in the management of patients on AS.
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Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Conduta Expectante , Idoso , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de TempoRESUMO
OBJECTIVES: To describe survival and cause of death in a nationwide cohort of Danish patients with prostate cancer undergoing radical prostatectomy (RP). To describe risk factors associated with prostate cancer mortality. PATIENTS AND METHODS: Observational study of 6489 men with localised prostate cancer treated with RP at six different hospitals in Denmark between 1995 and 2011. Survival was described using Kaplan-Meier estimates. Causes of death were obtained from the national registry and cross-checked with patient files. Cumulative incidence of death, any cause and prostate cancer-specific, was described using Nelson-Aalen estimates. Risk for prostate cancer death was analysed in a Cox multivariate regression model using the covariates: age, cT-category, PSA level and biopsy Gleason score. RESULTS: The median follow-up was 4 years. During follow-up, 328 patients died, 109 (33.2%) from prostate cancer and 219 (66.8%) from other causes. Six patients (0.09%) died ≤30 days of RP. In multivariate analysis, cT-category was a predictor of prostate cancer death (P < 0.001). Compared with T1 disease, both cT2c (hazard ratio [HR] 2.2) and cT3 (HR 7.2) significantly increased the risk of prostate cancer death. For every doubling of PSA level the risk of prostate cancer death was increased by 34.8% (P < 0.001). Biopsy Gleason score 4 + 3 and ≥8 were associated with an increased risk of prostate cancer death compared with biopsy Gleason score ≤ 6 of 2.3 and 2.7 (P = 0.003), respectively. The cumulative hazard of all-cause and prostate cancer-specific mortality after 10 years was 15.4% (95% confide3nce interval [CI] 13.2-17.7) and 6.6% (95% CI 4.9-8.2) respectively. CONCLUSIONS: We present the first survival analysis of a complete, nationwide cohort of men undergoing RP for localised prostate cancer. The main limitation of the study was the relatively short follow-up. Interestingly, our national results are comparable to high-volume, single institution, single surgeon series.
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Prostatectomia/mortalidade , Neoplasias da Próstata/cirurgia , Idoso , Dinamarca/epidemiologia , Métodos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/metabolismo , Prostatectomia/métodos , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND AND OBJECTIVE: To investigate risk factors associated with positive surgical margins (PSM) and biochemical recurrence (BR) in organ confined tumors (pT2) after radical prostatectomy (RP) for localized prostate cancer (PCa). METHODS: Between 1995 and 2011, 1,649 patients underwent RP at our institution. The study includes the 1,133 consecutive patients with pT2 tumors at final histopathology. Logistic regression analysis was used for risk of PSM. Risk of BR, defined as the first PSA ≥ 0.2 ng/ml, was analyzed with Kaplan-Meier and Cox regression analysis. RESULTS: Median follow-up was 3.6 years (range: 0.5-15.5 years). In logistic regression, NS surgery was independently associated with an increased risk of pT2 PSM (OR = 1.68, 95% CI: 1.3-2.0, P = 0.01) relative to non-NS surgery. NS surgery was not independently associated with BR but the interaction of PSM and NS surgery trended (P = 0.08) to increase the risk of BR compared to PSM and non-NS surgery. CONCLUSION: Several factors influence the risk of pT2 PSMs in radical prostatectomy. In our cohort pT2 PSM is associated with NS surgery and trend to increase risk of BR compared to non-NS surgery. The optimal selection of candidates for NS surgery is still not clear.
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Recidiva Local de Neoplasia/sangue , Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tratamentos com Preservação do Órgão , Próstata/inervação , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVE: To investigate how location of positive surgical margins (PSM) in pT2 tumors affect the risk of biochemical recurrence (BR). METHODS: The study includes 1,133 consecutive patients from 1995 until end of 2011, who had organ-confined disease (pT2) following RP. The location of PSM was stratified into apical and non-apical. BR was defined as the first PSA ≥ 0.2 ng/ml after RP. Risk of BR was analyzed with Kaplan-Meier and Cox regression analysis. RESULTS: Median follow-up was 3.6 years (range: 0.5-15.5 years). The overall pT2 PSM rate was 26.3%. Overall, a pT2 with PSM had a 3.1-fold increased risk of BR compared to margin negative patients. Patients with pT2 apical and non-apical PSM had a 5-year biochemical recurrence-free survival of 84.9% (95% CI: 77.6-92.2%) and 78.6% (95% CI: 71.3-85.9%), respectively. In multivariate analysis, pT2 apical and non-apical PSM was individually associated with a 2.2- and 3.8-fold increased risk of BR compared to margin negative patients. CONCLUSION: In our cohort the location of pT2 PSM was associated with time to BR, that is, patients with non-apical pT2 PSM endured the highest risk of BR compared to apical PSM. This may indicate that not all patients with pT2 PSM should be offered adjuvant therapy.
Assuntos
Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/etiologia , Complicações Pós-Operatórias , Prostatectomia , Neoplasias da Próstata/cirurgia , Adulto , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Neoplasias da Próstata/complicações , Neoplasias da Próstata/patologia , Fatores de RiscoRESUMO
BACKGROUND: The Danish attitude for diagnosis and treatment of early localized prostate cancer (PCa) has historically been conservative. Denmark introduced radical prostatectomy (RP) as the last of the Nordic countries in 1995. However, a rapid increment in the Danish incidence of PCa is indicative of a shift in attitude with increasing opportunistic PSA testing. This had led to an increasing number of RPs being performed in Denmark. The objective of this study was to analyze changes in preoperative characteristics over time for the complete cohort of 6489 men who underwent RP between 1995 and 2011. Our hypothesis was that an increasing amount of men undergo RP for lower risk PCa. MATERIAL AND METHODS: All patients operated from 1995 to 2011 were identified via patient files and registries. Changes over time in age at surgery, preoperative PSA, clinical T-category, biopsy Gleason score (GS), and D'Amico classification are described. Tests for statistically significant changes were performed. RESULTS: Median age increased from 61.4 to 64.8 years (p < 0.0001) during the 16-year period. Median PSA declined from 11.5 to 7.9 ng/ml (p < 0.0001). Distribution of biopsy GS changed significantly, especially after 2005. Biopsy GS = 7 was found in 20.2% of the patients in 2005 compared to 57.1% in 2011. The proportion of T1 disease increased from 32% to 56%. Significant changes in percentage of patients according to the D'Amico classification were found. After 2005 the proportion of intermediate-risk patients increased significantly. The proportion of patients age 70 or above increased from 2% to 13% in the period studies. CONCLUSION: Significant preoperative stage- and Gleason grade migration was found in this complete Danish nationwide cohort of patients undergoing RP during the past 16 years. This effect is most likely attributed to an increasing use of PSA as marker for early prostate cancer diagnosis in Denmark and new international guidelines for Gleason grading and scoring.
Assuntos
Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Biópsia/estatística & dados numéricos , Dinamarca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/epidemiologiaRESUMO
BACKGROUND: Radical cystectomy (RC) with urinary diversion is the recommended treatment for selected cases of non-metastatic high-risk non-muscle-invasive and muscle-invasive bladder cancer. It remains unknown whether robot-assisted laparoscopic cystectomy (RARC) offers any advantage in terms of safety compared to open cystectomy (ORC) in an Enhanced Recovery After Surgery (ERAS) setup. Blinded randomised controlled trials (RCTs) between RARC versus ORC have never been conducted in cystectomy patients. We will investigate the feasibility of conducting a double-blinded RCT comparing ORC with RARC with intra-corporal ileal conduit (iRARC) in an ERAS setup. METHODS: This is a single-centre, double-blinded, randomised (1:1) clinical feasibility study for patients with non-metastatic high-risk non-muscle-invasive or muscle-invasive bladder cancer scheduled for cystectomy. All participants are recruited from Rigshospitalet, Denmark. The planned sample size is 50 participants to investigate whether blinding of the surgical technique is feasible. Participants and postoperative caring physicians and nurses are blinded using a pre-study designed abdominal dressing and blinding of the patient's electronic health record. Study endpoints are assessed 90 days postoperatively. The primary aim is to study the frequency and pattern of unplanned unblinding after surgery and the number of participants who cannot guess the surgical technique at the day of discharge. Eleven secondary endpoints are assessed: length of stay, days alive and out of hospital, in-hospital complication rate, 30-day complication rate, 90-day complication rate, readmission rate, quality of life, blood loss, pain, rate of moderate/severe post-anaesthesia care unit (PACU) complications, and delirium. Participants are managed in an ERAS setup in both arms of the trial. DISCUSSION: We report on the design and objectives of a novel experimental feasibility study investigating whether blinding of the surgical technique in cystectomy patients is possible. This information is essential for the design of future blinded trials comparing ORC to RARC. There is a continued need to compare RARC and ORC in terms of both efficacy, safety, and oncological outcomes. Estimated end of study is March 2021. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03977831. Registered on the 6th of June 2019.