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BACKGROUND: The study aimed to validate the prognostic value of the Prostatype® risk score (P-score), which includes a three-gene signature and conventional risk factors, in a retrospective cohort. METHODS: All 716 patients diagnosed with prostate cancer from 2008 to 2010 at Skåne University Hospital, Sweden, were included. After excluding patients based on pathological and clinical eligibility criteria, RNA quality, and presence of metastases at diagnosis, a final cohort comprising 316 patients was further analyzed. Expression levels of three genes (IGFBP3, F3, and VGLL3) were measured in archived formalin-fixed paraffin-embedded core needle biopsies. The gene expression data were combined with clinical parameters (Gleason score, prostate-specific antigen, and clinical tumor stage) to calculate the P-score for each patient. Predictive performance of the P-score in terms of prostate cancer-specific mortality (PCSM), distant metastasis and adverse pathological outcomes were investigated. RESULTS: The P-score predicted both PCSM (hazard ratio [HR] = 1.6) and metastasis (HR = 1.46). The P-score had an area under curve (AUC) of 0.93 when predicting the PCSM risk at 10 years (95% confidence interval [CI]: 0.89-0.98), which was significantly better than both D'Amico (AUC: 0.81, 95% CI: 0.72-0.90, p < 0.001) and UCSF-CAPRA (AUC: 0.88, 95% CI: 0.80-0.96, p < 0.05). Decision curve analysis showed a higher net benefit of the P-score compared to both D'Amico and CAPRA. All three risk scores performed similarly in the prediction of distant metastases. For patients who underwent radical prostatectomy (RP), a higher P-score correlated with adverse pathological features such as pathologic tumor stage T3-4 (p < 0.0001) and ≥International Society of Urological Pathology grade group 3 (p < 0.0001). CONCLUSIONS: Our findings provide evidence for the prognostic value of the P-score. The P-score predicted the risk for PCSM more accurately than the D'Amico and CAPRA scores. Performance was similar when predicting the risk for development of distant metastases within 10 years. Moreover, the P-score correlated with adverse pathological outcomes in RP specimens. Thus, the P-score could provide useful information for patients and their doctors to make informed decisions at the time of diagnosis.
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Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Fatores de Risco , Gradação de Tumores , Prostatectomia , Medição de Risco , Fatores de TranscriçãoRESUMO
BACKGROUND: Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS). MATERIALS AND METHODS: Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8-10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis. RESULTS: Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0-5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50-0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49-0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse. CONCLUSION: Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Docetaxel , Antagonistas de Androgênios/uso terapêutico , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Doença Crônica , Hormônios/uso terapêutico , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Radical prostatectomy (RP) is a common surgical procedure with a risk of postoperative erectile dysfunction and urinary incontinence. There is a need for data on RP as a basis for quality assurance and benchmarking. METHODS: In 2015, prostatectomies in Sweden (PiS) form was implemented in the National Prostate Cancer Register (NPCR) of Sweden with data on pre-, peri- and post-operative variables. RESULTS: Out of all radical prostatectomies performed in 2016 in Sweden, 3096/3881 (80%) were registered in PiS. A total of 2605 (84%) were robot-assisted radical prostatectomy (RARP) and 491 (16%) were RRP (retropubic radical prostatectomy). RARP was performed by 91 surgeons of whom 47% operated more than 25 RP/year; and RRP was performed by 69 surgeons of whom 10% performed more than 25 RP/year. RARP had a longer operative time (median operating time: RARP 155 minutes [IQR 124-190]; RRP 129 minutes [IQR 105-171]; P < .001) but was associated with smaller bleeding (median intraoperative blood loss: RARP 100 mL [IQR 50-200], RRP 700 mL [IQR 500-1100]; P < .001). CONCLUSIONS: We report on a nationwide, population-based register with transparent reporting of data on the performance of radical prostatectomy. These data are needed as a basis for quality assurance with comparisons of results from individual surgeons and hospitals.
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Complicações Pós-Operatórias , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/cirurgia , Sistema de Registros/estatística & dados numéricos , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/epidemiologia , Suécia/epidemiologiaRESUMO
BACKGROUND: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. METHODS: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894. FINDINGS: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). INTERPRETATION: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. FUNDING: Steba Biotech.
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Bacterioclorofilas/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Vigilância da População , Prognóstico , Neoplasias da Próstata/patologia , Medição de Risco , Taxa de SobrevidaRESUMO
OBJECTIVES: To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. MATERIALS AND METHODS: An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. RESULTS: In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement κ 0.89) and they included: need for a training curriculum (inter-rater agreement κ 0.85); identification of learning needs (κ 0.83); development of the curriculum contents (κ 0.81); an overview of available curricula (κ 0.79); settings for robotic surgery training ((κ 0.89); assessment and training of trainers (κ 0.92); requirements for certification and patient safety (κ 0.83); and need for a universally standardised curriculum (κ 0.78). A training curriculum was proposed based on the above discussions. CONCLUSION: This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.
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Currículo , Robótica/educação , Procedimentos Cirúrgicos Urológicos/educação , Procedimentos Cirúrgicos Urológicos/métodos , Urologia/educação , Consenso , HumanosRESUMO
PURPOSE: Salvage radiotherapy (SRT) for biochemical recurrence (BCR) following radical prostatectomy (RP) should if possible be added at a prostate-specific antigen (PSA) level of <1-2 ng/mL. The value of positron emission tomography combined with computed tomography (PET/CT) at such low PSA values is not defined. The purpose was to determine what proportion of a well-defined cohort of hormone-naïve patients who were candidates for early salvage radiotherapy had (18)F-choline PET/CT findings suggesting metastases. MATERIALS AND METHODS: Patients with untreated BCR following RP, PSA <2 ng/mL, and Gleason score ≥7 or PSA doubling time ≤6 months underwent (18)F-choline PET/CT. Focal choline uptake in lymph nodes or skeletal sites was recorded. RESULTS: PET/CT indicated metastases in 16 (28 %) of 58 patients. In five (9 %) patients, the scans suggested bone metastases, and in 11 (19 %) patients, the scans suggested regional lymph node metastases only. For patients with PSA levels <1.0 ng/mL, the PET/CT scans indicated metastatic recurrence in 25 %. CONCLUSIONS: (18)F-choline PET/CT may be valuable for selecting patients with BCR following RP for SRT or experimental treatment of oligometastases, even at low PSA values.
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Diagnóstico Precoce , Recidiva Local de Neoplasia/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Idoso , Colina , Terapia Combinada , Diagnóstico Diferencial , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/terapia , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/terapia , Cuidados Pós-Operatórios/métodos , Neoplasias da Próstata/secundário , Neoplasias da Próstata/terapia , Curva ROC , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
BACKGROUND: Low nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to be associated with poor prognosis in several cancer forms e.g. breast, ovarian, colorectal, prostate cancer and malignant melanoma. The aim of this study was to examine the prognostic impact of RBM3 expression in urinary bladder cancer. METHODS: Immunohistochemical RBM3 expression was examined in tumours from 343 patients with urothelial bladder cancer. Chi-square and Spearman's correlation tests were applied to explore associations between RBM3 expression and clinicopathological characteristics. The impact of RBM3 expression on disease-specific survival (DSS), 5-year overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier analysis and Cox proportional hazards modelling. RESULTS: Reduced nuclear RBM3 expression was significantly associated with more advanced tumour (T) stage (p <0.001) and high grade tumours (p=0.004). Negative RBM3 expression was associated with a significantly shorter DSS (HR=2.55; 95% CI 1.68-3.86)) and 5-year OS (HR=2.10; 95% CI 1.56-2.82), also in multivariable analysis (HR=1.65; 95% CI 1.07-2.53 for DSS and HR=1.54; 95% CI 1.13-2.10 for 5-year OS). In patients with Ta and T1 tumours expressing reduced RBM3 levels, Kaplan-Meier analysis revealed a significantly shorter PFS (p=0.048) and 5-year OS (p=0.006). CONCLUSION: Loss of RBM3 expression is associated with clinically more aggressive tumours and an independent factor of poor prognosis in patients with urothelial bladder cancer and a potentially useful biomarker for treatment stratification and surveillance of disease progression.
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Carcinoma de Células de Transição/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVE: To investigate how often positron emission tomography/computed tomography (PET/CT) scans, with both (18)F-fluorocholine and (18)F-fluoride as markers, add clinically relevant information for patients with prostate cancer who have high-risk tumours and a normal or inconclusive planar bone scan. PATIENTS AND METHODS: Patients with prostate cancer with prostate specific antigen (PSA) levels between 20 and 99 ng/mL and/or Gleason score 8-10 tumours, planned for treatment with curative intent based on routine staging with a negative or inconclusive bone scan, were further investigated with a (18)F-fluorocholine and a (18)F-fluoride PET/CT. None of the patients received hormonal therapy before the staging procedures were completed. RESULTS: For 50 of the 90 included patients (56%) one or both PET/CT scans indicated metastases. (18)F-fluorocholine PET/CT indicated lymph node metastases and/or bone metastases in 35 patients (39%). (18)F-fluoride PET/CT was suggestive for bone metastases in 37 patients (41%). In 18 patients (20%) the PET/CT scans indicated widespread metastases, leading to a change in therapy intent from curative to non-curative. Of the patients with positive scans, 74% had Gleason score 8-10 tumours. Of the patients with Gleason score 8-10 tumours, 64% had positive scans. CONCLUSIONS: PET/CT scans with (18)F-fluorocholine and (18)F-fluoride commonly detect metastases in patients with high-risk prostate cancer and a negative or inconclusive bone scan. For 20% of the patients the results of the PET/CT scans changed the treatment plan.
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Colina/análogos & derivados , Fluoretos , Radioisótopos de Flúor , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Humanos , Metástase Linfática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico por imagemRESUMO
OBJECTIVE: To introduce salvage prostatectomy in Denmark. Prior to this, no national curative treatment for recurrent prostate cancer following radiation therapy existed in Denmark. This pilot study represent our initial experiences and the feasibility of performing salvage robot-assisted radical prostatectomy for true local, high-risk recurrence after initial therapy with external beam radiation for high-risk prostate cancer. RESULTS: Five patients underwent sRARP between April 2020 and July 2021. All patients were discharged within 48 h and no major complications were observed within 3 months. All patients had unmeasurable PSA (< 0.1 ng/ml) at follow-up 6 months after surgery. One patient with longer follow-up than 6 months experienced biochemical recurrence. At 3-months follow-up all patients reported considerable incontinence, at 6-month follow-up, pad usage decreased to 1 or 2 pads daily. Based on our initial results, the idea to introduce sRARP as a nationwide option remains and further patients will be included to establish the true role of sRARP in patients with recurrence after primary radiotherapy for PCa.
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Recidiva Local de Neoplasia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Dinamarca , Humanos , Masculino , Recidiva Local de Neoplasia/cirurgia , Projetos Piloto , Antígeno Prostático Específico , Prostatectomia/métodos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Terapia de Salvação/métodos , Resultado do TratamentoRESUMO
Background and purpose: The treatment of biochemical recurrence (BCR) after prostatectomy is challenging as the site of the recurrence is often undetectable. Our aim was to test a personalised treatment concept for BCR based on PSA kinetics during salvage radiotherapy (SRT) combined with prostate-specific membrane antigen positron emission tomography (PSMA-PET). Materials and methods: This phase II trial included 100 patients with BCR. PSMA-PET was performed at baseline. PSA was measured weekly during SRT. Initially, 70 Gy in 35 fractions was prescribed to the prostate bed. Radiotherapy was adapted after 50 Gy. Non-responders (PSA still ≥ 0.15 ng/mL) received sequential lymph node irradiation with a boost to PSMA-PET positive lesions, while responders (PSA < 0.15 ng/mL) continued SRT as planned. PET-findings were only taken into consideration for treatment planning in case of PSA non-response after 50 Gy. Results: Data from 97 patients were eligible for analysis. Thirty-four patients were classified as responders and 63 as non-responders. PSMA-PET was positive in 3 patients (9%) in the responder group and in 22 (35%) in the non-responder group (p = 0.007). The three-year failure-free survival was 94% for responders and 68% for non-responders (median follow-up 38 months). There were no significant differences in physician-reported urinary and bowel toxicity. Patient-reported diarrhoea at end of SRT was more common among non-responders. Conclusion: This new personalised treatment concept with intensified SRT based on PSA response demonstrated a high tumour control rate in both responders and non-responders. These results suggest a clinically significant effect with moderate side effects in a patient group with otherwise poor prognosis. PSMA-PET added limited value. The treatment approach is now being evaluated in a phase III trial.Clinical trial registration numbers: NCT02699424&ISRCTN45905321.
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OBJECTIVE: Post-treatment prostate biopsy side-effects were evaluated in patients with locally advanced prostate cancer on endocrine therapy alone or combined with radiotherapy in the Scandinavian Prostate Cancer Group-7 randomized trial. MATERIAL AND METHODS: One-hundred and twenty patients underwent transrectalultrasound-guided biopsy, and were requested to complete a questionnaire on side-effects occurring within 7 days' follow-up. RESULTS: The questionnaire was returned by 109 patients (91%) (endocrine therapy only 52%, combined endocrine therapy and radiotherapy 48%). Previous therapy had no significant influence on pain, urinary flow, haematuria or haematospermia. Pain at biopsy was reported in 63% (mild, 57%; moderate, 5.6%; severe, one patient) and pain at follow-up in 31% (mild, 27%; moderate, four patients). Haematuria (mean duration 2.2 days) was reported in 41%, and reduced urinary flow in 20% (mild, 18%; severe: four patients; no patient had urinary retention). Haematospermia was scarce. No patient reported urinary tract infection. Rectal bleeding occurred in 18% in the endocrine and 35% in the combined therapy group (p = 0.047), with a mean duration of 1.6 and 2.2 days, respectively (p = 0.031). In logistic regression analysis, a trend towards increased rectal bleeding was found in patients on combined endocrine therapy and radiotherapy (odds ratio 2.4, p = 0.050). CONCLUSION: Patient-reported post-treatment prostate biopsy side-effects were mild and self-limiting.
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Biópsia/efeitos adversos , Tratamento Farmacológico/métodos , Hematúria/epidemiologia , Hemospermia/epidemiologia , Dor/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Radioterapia/métodos , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Terapia Combinada , Quimioterapia Combinada , Flutamida/uso terapêutico , Seguimentos , Hematúria/etiologia , Hemospermia/etiologia , Humanos , Incidência , Leuprolida/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND OBJECTIVE: Few studies have investigated the association between surgical volume and outcome of robot-assisted radical prostatectomy (RARP) in an unselected cohort. We sought to investigate the association between surgical volume with peri-operative and short-term outcomes in a nation-wide, population-based study group. METHODS: 9,810 RARP's registered in the National Prostate Cancer Register of Sweden (2015-2018) were included. Associations between outcome and volume were analyzed with multivariable logistic regression including age, PSA-density, number of positive biopsy cores, cT stage, Gleason score, and extent of lymph node dissection. RESULTS: Surgeons and hospitals in the highest volume group compared to lowest group had shorter operative time; surgeon (OR 9.20, 95% CI 7.11-11.91), hospital (OR 2.16, 95% CI 1.53-3.06), less blood loss; surgeon (OR 2.58. 95% CI 2.07-3.21) hospital (no difference), more often nerve sparing intention; surgeon (OR 2.89, 95% CI 2.34-3.57), hospital (OR 2.02, 95% CI 1.66-2.44), negative margins; surgeon (OR 1.90, 95% CI 1.54-2.35), hospital (OR 1.28, 95% CI 1.07-1.53). There was wide range in outcome between hospitals and surgeons with similar volume that remained after adjustment. CONCLUSIONS: High surgeon and hospital volume were associated with better outcomes. The range in outcome was wide in all volume groups, which indicates that factors besides volume are of importance. Registration of surgical performance is essential for quality control and improvement.
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Prostatectomia/instrumentação , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Hospitais com Alto Volume de Atendimentos , Hospitais com Baixo Volume de Atendimentos , Humanos , Excisão de Linfonodo , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Gradação de Tumores , Duração da Cirurgia , Período Perioperatório , Neoplasias da Próstata/patologia , Cirurgiões , Suécia , Resultado do TratamentoRESUMO
BACKGROUND: Treatment adaptation based on tumour biomarker response during radiotherapy of prostate cancer, could be used for both escalation and de-escalation of radiation doses and volumes. To execute an adaptation involving extension of treatment volumes during radiation can however be restricted by the doses already delivered. The aim of this work was to develop a treatment planning method that addresses this challenge. MATERIAL AND METHODS: A volumetric-modulated-arc-therapy (VMAT) planning method with sequential plan-on-plan optimization was developed for a prospective phase II trial including 100 patients on salvage radiotherapy (SRT) for prostate cancer recurrence. A treatment adaptation was performed after five weeks of SRT based on prostate-specific antigen response during this phase of the treatment. This involved extension of treatment volumes for non-responders (n = 64) to include pelvic lymph nodes and boost to 68Gallium-Prostate-Specific-Membrane-Antigen-Positron-Emission-Tomography positive lesions. This method was evolved by introducing an EQD2 (equivalent dose in 2.0 Gy fractions) correction of the base plan for improved dose coverage. RESULTS: All dose-volume criteria for target coverage were met for the non-responders when based on physical dose. An EQD2 correction of the base plan for non-responders, implemented for the final 29 patients, led to a statistically significant improvement in dose coverage as compared to the 35 patients treated without EQD2 correction. CONCLUSIONS: This is to our knowledge the only study presented on biomarker-guided sequential VMAT radiotherapy using a plan-on-plan technique in the pelvis. By using a biologically adapted technique an improved target coverage was achieved without compromising doses to organs at risk.
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BACKGROUND AND PURPOSE: Biochemical recurrence after prostatectomy is commonly treated with salvage radiotherapy (SRT). In this prospective observational study we investigated the PSA decay rate, determined by predefined serial PSA measurements during SRT, as a predictor for treatment outcome. MATERIALS AND METHODS: Between 2013 and 2016, 214 patients were included in the study. The prescribed dose to the prostate bed was 70 Gy in 35 fractions (7 weeks) without hormonal treatment. PSA was measured weekly during SRT. Assuming first order kinetics, a PSA decay-rate constant (k) was calculated for 196 eligible patients. The ability of k to predict disease progression was compared with known clinical prediction parameters using Cox regression, logistic regression and ROC analyses. Disease progression was defined as continuously rising PSA after SRT, PSA increase by ≥0.2 ng/ml above nadir after SRT, hormonal treatment or clinical progression. RESULTS: After a median follow up of 4.7 years the estimated failure-free survival at 5 years was 56%. The PSA decay-rate constant (k) was found to be the strongest predictor of disease progression in both uni-and multivariable analyses. CONCLUSION: The addition of k to established clinical variables significantly improves the possibility to predict treatment outcome after SRT and could be used to personalize future therapies.
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BACKGROUND: Adjuvant chemotherapy is standard treatment for other solid tumours, but to date has not proven effective in prostate cancer. OBJECTIVE: o evaluate whether six cycles of docetaxel alone improve biochemical disease-free survival after radical prostatectomy for high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Open-label, randomised multinational phase 3 trial. Enrolment of 459 patients after prostatectomy. INCLUSION CRITERIA: high-risk pT2 margin positive or pT3a Gleason score ≥4+3, pT3b, or lymph node positive disease Gleason score ≥3+4. Patients assigned (1:1) to either six cycles of adjuvant docetaxel 75mg/m2 every 3 wk without daily prednisone (Arm A) or surveillance (Arm B) until endpoint was reached. Primary endpoint was prostate-specific antigen progression ≥0.5 ng/ml. INTERVENTION: Docetaxel treatment after prostatectomy. RESULTS AND LIMITATIONS: Median time to progression, death, or last follow-up was 56.8 mo. Primary endpoint was reached in 190/459 patients-the risk of progression at 5 yr being 41% (45% in Arm A and 38% in Arm B). There was evidence of nonproportional hazards in Kaplan-Meier analysis, so we used the difference in restricted mean survival time as the primary estimate of effect. Restricted mean survival time to endpoint was 43 mo in Arm A versus 46 mo in Arm B (p=0.06), a nonsignificant difference of 3.2 mo (95% confidence interval: 6.7 to -1.5 mo). A total of 116 serious adverse events were recorded in Arm A and 41 in Arm B with no treatment-related deaths. Not all patients received docetaxel by protocol. The endpoint is biochemical progression and some patients received radiation treatment before the endpoint. CONCLUSIONS: Docetaxel without hormonal therapy did not significantly improve biochemical disease-free survival after radical prostatectomy. PATIENT SUMMARY: In this randomised trial, we tested whether chemotherapy after surgery for high-risk prostate cancer decreases the risk of a rising prostate-specific antigen. We found no benefit from docetaxel given after radical prostatectomy.
Assuntos
Antineoplásicos/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Conduta Expectante , Idoso , Antineoplásicos/efeitos adversos , Quimioterapia Adjuvante , Progressão da Doença , Intervalo Livre de Doença , Docetaxel/efeitos adversos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasia Residual , Período Pós-Operatório , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Prostatectomia/efeitos adversos , Neoplasias da Próstata/sangue , Fatores de Risco , Taxa de SobrevidaAssuntos
Biomarcadores Tumorais/sangue , Programas de Rastreamento , Educação de Pacientes como Assunto , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Detecção Precoce de Câncer/efeitos adversos , Humanos , Masculino , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/normas , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Projetos Piloto , Neoplasias da Próstata/sangue , Sensibilidade e Especificidade , Inquéritos e Questionários , Suécia/epidemiologia , Procedimentos DesnecessáriosRESUMO
BACKGROUND: Urothelial bladder cancer (UBC) is a disease that often is discovered when the tumour is non-muscle invasive, i.e. in Ta or T1 stage. Some patients will progress into muscle-invasive disease, a potentially deadly condition. Although there are some prognostic models, the need for prognostic and predictive biomarkers is considerate and urgent. Membranous expression of podocalyxin-like protein 1 (PODXL) and low expression of the RNA-binding motif 3 (RBM3) has previously been shown to be associated with an aggressive tumour phenotype and poor prognosis in several forms of cancer, including UBC. In this study, we sought to validate the prognostic impact of PODXL and RBM3 in an independent cohort of UBC. METHODS: Using tissue microarrays and immunohistochemistry, PODXL and RBM3 expression was evaluated in 272 incident UBC cases from the prospective, population-based cohort study Malmö Diet and Cancer. Kaplan-Meier analysis and Cox proportional hazards modelling were used to evaluate the prognostic impact of these markers on 5-year overall survival (OS). RESULTS: In line with previous studies, both membranous PODXL expression and low RBM3 expression was significantly associated with disadvantageous clinicopathological features. Membranous PODXL expression was significantly associated with a reduced 5-year overall survival in the entire cohort (univariable HR 3.28; 95% CI 1.89-5.69), but this association did not remain significant in multivariable analysis. In T1 tumours, PODXL was significantly associated with reduced survival in univariable analysis (HR = 2.83; 95% CI 1.04-7.72) and borderline significant in multivariable analysis (HR = 2.60; 95% CI 0.91-7.39). Low RBM3 expression was an independent predictor of a reduced survival in the entire cohort (univariable HR 3.19; 95% CI 2.02-5.04, and multivariable HR 1.85; 95% CI 1.11-3.09), and in T1 tumours (univariable HR 2.64; 95% CI 1.11-6.27, and multivariable HR 2.63; 95% CI 1.01-6.84). CONCLUSIONS: A link between membranous PODXL expression and clinically more aggressive tumours was further confirmed, but PODXL expression was not an independent prognostic biomarker in this study. Low RBM3 expression was validated as an independent factor of poor prognosis in UBC, including T1 disease. These findings suggest that these biomarkers could be useful in stratifying patients with non-muscle invasive disease for more aggressive first line treatment.
RESUMO
Prostate cancer units - hubs in the future care of men with prostate cancer Prostate cancer is the most common form of cancer in Sweden. The past decade has seen a tremendous development of new methods for diagnosing, staging, treating and rehabilitating men with suspicious or confirmed prostate cancer. This development necessitates a multidisciplinary and multiprofessional approach to the management of men with suspicious or confirmed prostate cancer. A recent survey showed that currently few Swedish men with prostate cancer receive the quality of care that is outlined in the national clinical guidelines. Specialised prostate cancer units are increasingly common in Europe, but as yet there are no such units in Sweden. We believe that the creation of prostate cancer units in Sweden would be an essential step forward, towards an improved future care of men with prostate cancer.
Assuntos
Serviços Centralizados no Hospital , Neoplasias da Próstata , Humanos , Masculino , Programas de Rastreamento , Guias de Prática Clínica como Assunto , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Qualidade da Assistência à Saúde , Suécia/epidemiologiaRESUMO
OBJECTIVE: Functional outcomes after ileal bladder substitution reflect the expectations of future patients at a particular centre. The aim of this study was to use validated questionnaires and a pad-weighing test to investigate functional outcomes after neobladder reconstruction at long-term follow-up in patients at a single centre. MATERIALS AND METHODS: During 2005 - 2015, 75 patients received a Studer ileal bladder substitute at the Department of Urology, Malmö. Forty-six of these patients were alive for follow-up and were evaluated using the pad-weighing test and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), the Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF). RESULTS: Five of 37 evaluable patients (14%) were considered fully continent, reporting a pad-weighing test result of 0â g and an ICIQ-UI-SF score of 0. The median ICIQ-UI-SF score was 8 [interquartile range (IQR) 3-11], and seven patients (17%) were continent according to the ICIQ-UI-SF score only. In the pad-weighing test, 28 out of 37 patients (76%) reported 0â g day-time leakage whereas only 12 out of 37 patients (32%) reported 0â g night-time leakage. At follow-up, nine out of 39 (23%) of evaluable male patients were potent. The median ICIQ-UI-SF score was significantly lower during the second half of the study period [4 (IQR 0-8) vs 10 (IQR 6-14); p = .003]. The inverse applied to the median IIEF score [5 (IQR 3-12) vs 2 (IQR 1-4); p = .02]. CONCLUSIONS: Functional outcomes at long-term follow-up after radical cystectomy and Studer ileal bladder substitute were at best modest in this series. Better outcomes during the second half of the study period might be explained by improved patient selection and a refined surgical technique, but possibly also by longer follow-up of patients during the first half of the period resulting in a more pronounced time-dependent decline in functional outcomes.
Assuntos
Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Disfunção Erétil/epidemiologia , Íleo/transplante , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Incontinência Urinária/epidemiologia , Idoso , Feminino , Seguimentos , Humanos , Tampões Absorventes para a Incontinência Urinária , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Autorrelato , Disfunções Sexuais Fisiológicas/epidemiologia , Inquéritos e Questionários , Resultado do Tratamento , Incontinência Urinária/etiologia , Coletores de UrinaRESUMO
BACKGROUND: In observational studies, men with prostate cancer treated with gonadotropin-releasing hormone (GnRH) agonists had a higher risk of cardiovascular disease (CVD) compared to men who had undergone orchiectomy. However, selection bias may have influenced the difference in risk. OBJECTIVE: To investigate the association of type of androgen deprivation therapy (ADT) with risk of CVD while minimising selection bias. DESIGN, SETTING, AND PARTICIPANTS: Semi-ecologic study of 6556 men who received GnRH agonists and 3330 men who underwent orchiectomy as primary treatment during 1992-1999 in the Prostate Cancer Database Sweden 3.0. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured the proportion of men who received GnRH agonists as primary treatment in 580 experimental units defined by healthcare provider, diagnostic time period, and age at diagnosis. Incident or fatal CVD events in units with high and units with low use of GnRH agonists were compared. Net and crude probabilities were also analysed. RESULTS AND LIMITATIONS: The risk of CVD was similar between units with the highest and units with the lowest proportion of GnRH agonist use (relative risk 1.01, 95% confidence interval [CI] 0.93-1.11). Accordingly, there was no difference in the net probability of CVD after GnRH agonist compared to orchiectomy (hazard ratio 1.02, 95% CI 0.96-1.09). The 10-yr crude probability of CVD was 0.56 (95% CI 0.55-0.57) for men on GnRH agonists and 0.52 (95% CI 0.50-0.54) for men treated with orchiectomy. The main limitation was the nonrandom allocation to treatment, with younger men with lower comorbidity and less advanced cancer more likely to receive GnRH agonists. CONCLUSION: Our data do not support previous observations that GnRH agonists increase the risk of CVD in comparison to orchiectomy. PATIENT SUMMARY: We found a similar risk of cardiovascular disease between medical and surgical treatment as androgen deprivation therapy for prostate cancer.