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OBJECTIVES: To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk-) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk- NSGCT. PATIENTS AND METHODS: Observational prospective population-based study of patients diagnosed 2008-2019 with CS IIA Mk- NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk- disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. RESULTS: Overall, 126 patients with CS IIA Mk- NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6-18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk- NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. CONCLUSIONS: Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk- NSGCT had a high rate of cancer and a low rate of teratoma.
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Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/terapia , Estudos Prospectivos , Adulto , Adulto Jovem , Tomografia Computadorizada por Raios X , Excisão de Linfonodo , Biomarcadores Tumorais , Pessoa de Meia-Idade , Adolescente , Metástase Linfática , Suécia/epidemiologiaRESUMO
OBJECTIVE: To validate Vergouwe's prediction model using the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) RETROP database and to define its clinical utility. MATERIALS AND METHODS: Vergouwe's prediction model for benign histopathology in post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) uses the following variables: presence of teratoma in orchiectomy specimen; pre-chemotherapy level of alpha-fetoprotein; ß-Human chorionic gonadotropin and lactate dehydrogenase; and lymph node size pre- and post-chemotherapy. Our validation cohort consisted of patients included in RETROP, a prospective population-based database of patients in Sweden and Norway with metastatic nonseminoma, who underwent PC-RPLND in the period 2007-2014. Discrimination and calibration analyses were used to validate Vergouwe's prediction model results. Calibration plots were created and a Hosmer-Lemeshow test was calculated. Clinical utility, expressed as opt-out net benefit (NBopt-out ), was analysed using decision curve analysis. RESULTS: Overall, 284 patients were included in the analysis, of whom 130 (46%) had benign histology after PC-RPLND. Discrimination analysis showed good reproducibility, with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95% confidence interval 0.77-0.87) compared to Vergouwe's prediction model (AUC between 0.77 and 0.84). Calibration was acceptable with no recalibration. Using a prediction threshold of 70% for benign histopathology, NBopt-out was 0.098. Using the model and this threshold, 61 patients would have been spared surgery. However, only 51 of 61 were correctly classified as benign. CONCLUSIONS: The model was externally validated with good reproducibility. In a clinical setting, the model may identify patients with a high chance of benign histopathology, thereby sparing patients of surgery. However, meticulous follow-up is required.
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Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Espaço Retroperitoneal/cirurgia , Excisão de Linfonodo/métodos , Neoplasias Embrionárias de Células Germinativas/patologia , FibroseRESUMO
Cystoscopy is the gold standard for surveillance of non-muscle invasive bladder cancer (NMIBC), but the procedure is invasive and has suboptimal accuracy. The aim of this study was to investigate the potential of analyzing urine samples for the presence of urine tumor DNA (utDNA) to replace cystoscopy for surveillance of bladder cancer recurrence. In this longitudinal, prospective, and observational study, 47 patients were followed for recurrence for 2 years, involving analysis of utDNA using the BladMetrix DNA methylation biomarker test at each cystoscopy. In total, utDNA was detected in 21/23 recurrences (91% sensitivity), including 5/5 T1, T2, and carcinoma in situ (CIS) tumors (100%) and 10/12 Ta tumors (83%), with < 1% false-negative test results. Importantly, utDNA analysis showed the potential to reduce the number of cystoscopies by 55%, benefitting 79% of the patients. Eleven of 23 recurrences (48%) were detected earlier with utDNA than with cystoscopy, and distinct patterns of residual utDNA post-surgery indicated minimal residual disease (MRD) or field effect in 6% and 15% of the patients, respectively. In conclusion, utDNA analysis shows high sensitivity to detect tumor recurrence, potential to reduce the number of cystoscopies, and promise to guide patient-specific surveillance regimens.
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Background and objective: There is an unmet need to avoid long-term morbidity associated with standard cytotoxic treatment for low-volume metastatic seminoma. Our aim was to assess the oncological efficacy and surgical safety of retroperitoneal lymph node dissection (RPLND) as treatment in a population-based cohort of metastatic seminoma patients with limited retroperitoneal lymphadenopathy. Methods: Sixty-two seminoma patients in Norway and Sweden were included in the cohort from 2019 to 2022. Patients with lymphadenopathy ≤3 cm, having primary clinical stage (CS) IIA/B or CS I with a relapse, were operated with uni- or bilateral template RPLND, open or robot assisted. The outcome measures included surgical complications as per Clavien-Dindo, and Kaplan-Meier survival estimates for 24-mo progression-free survival (PFS) and overall survival (OS). Key findings and limitations: In the cohort, 33 (53%) had CS I with a relapse during surveillance, six (10%) CS I with a relapse following adjuvant chemotherapy, and 23 (37%) initial CS IIA/B. Metastatic seminoma was verified in 58 patients (94%) with a median largest diameter of 18 mm (interquartile range [IQR] 13-24). Robot-assisted RPLND was performed in 40 patients (65%). Clavien-Dindo III complications were observed in three patients (5%); no grade ≥IV complications occurred. Eighteen patients (29%) received adjuvant chemotherapy after surgery. The median follow-up was 23 mo (IQR 16-30), and recurrence occurred in six patients (10%) after a median of 8 mo (IQR 4-14). PFS was 90% (95% confidence interval: 0.86-1) and OS was 100% at 24 mo. Conclusions and clinical implications: RPLND as primary treatment is an option for selected low-stage seminomas with a limited burden of disease, showing low complications and low relapse rates, with the potential to reduce long-term morbidity. Patient summary: In seminoma patients with limited metastatic spread, surgery is a treatment option offering an alternative to chemotherapy or radiation. This paper covers the first 62 patients operated in Norway and Sweden.
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OBJECTIVE: Hexaminolevulinate (HAL) is an optical imaging agent used with fluorescence cystoscopy (FC) for the detection of non-muscle-invasive bladder cancer (NMIBC). Guidelines from the European Association of Urology (EAU) and a recent, more detailed European expert consensus statement agree that HAL-FC has a role in improving detection of NMIBC and provide recommendations on situations for its use. Since the publication of the EAU guidelines and the European consensus statement, new evidence on the efficacy of HAL-FC in reducing recurrence of NMIBC, compared with white light cystoscopy (WLC), have been published. MATERIAL AND METHODS: To consider whether these new trials have an impact on the expert guidelines and on clinical practice (e.g. supporting existing recommendations or providing evidence for a change or expansion of practice), a group of bladder cancer experts from Denmark, Finland, Norway and Sweden met to address the following questions: What is the relevance of the new data on HAL-FC for clinical practice in managing NMIBC? What impact do the new data have on European guidelines? How could HAL-FC be used in clinical practice? and What further information on HAL-FC is required to optimize the management of NMIBC? RESULTS AND CONCLUSIONS: This article reports the outcomes of the discussion at the Nordic expert panel meeting, concluding that, in line with European guidance, HAL-FC has an important role in the initial detection of NMIBC and for follow-up of patients to assess tumour recurrence after WLC. It provides practical advice, with an algorithm on the use of this diagnostic procedure for urologists managing NMIBC.
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Ácido Aminolevulínico/análogos & derivados , Cistoscopia/métodos , Fármacos Fotossensibilizantes , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Consenso , Europa (Continente) , Fluorescência , Humanos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Cystoscopy is the gold standard for bladder cancer detection, but is costly, invasive and has imperfect diagnostic accuracy. We aimed to identify novel and accurate DNA methylation biomarkers for non-invasive detection of bladder cancer in urine, with the potential to reduce the number of cystoscopies among hematuria patients. RESULTS: Biomarker candidates (n = 32) were identified from methylome sequencing of urological cancer cell lines (n = 16) and subjected to targeted methylation analysis in tissue samples (n = 60). The most promising biomarkers (n = 8) were combined into a panel named BladMetrix. The performance of BladMetrix in urine was assessed in a discovery series (n = 112), consisting of bladder cancer patients, patients with other urological cancers and healthy individuals, resulting in 95.7% sensitivity and 94.7% specificity. BladMetrix was furthermore evaluated in an independent prospective and blinded series of urine from patients with gross hematuria (n = 273), achieving 92.1% sensitivity, 93.3% specificity and a negative predictive value of 98.1%, with the potential to reduce the number of cystoscopies by 56.4%. CONCLUSIONS: We here present BladMetrix, a novel DNA methylation urine test for non-invasive detection of bladder cancer, with high accuracy across tumor grades and stages, and the ability to spare a significant number of cystoscopies among patients with gross hematuria.
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Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Metilação de DNA , Hematúria/diagnóstico , Hematúria/genética , Humanos , Estudos Prospectivos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/urinaRESUMO
BACKGROUND: The distribution of retroperitoneal lymph node metastases for patients with nonseminoma and a residual tumour of 10-49 mm in a population-based setting is unknown. This information is needed to justify selection of patients for a unilateral template resection. OBJECTIVE: To describe the location of retroperitoneal metastases and recurrences in patients with nonseminoma germ cell tumour (NSGCT) with a residual tumour of 10-49 mm. DESIGN, SETTING, AND PARTICIPANTS: RETROP is a population-based prospective observational mapping study of 213 patients in Sweden and Norway with a retroperitoneal residual tumour of 10-49 mm who underwent postchemotherapy retroperitoneal lymph node dissection for metastatic NSGCT during 2007-2014 with median follow-up of 100 mo. Patients were classified according to the testis primary tumour and the distribution of unilateral or bilateral lymph node metastases (with reference to the aorta) present on pre- and/or postchemotherapy computed tomography (CT) scans. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The distribution and rate of teratoma or cancer in unilateral or bilateral retroperitoneal fields and the location and rate of retroperitoneal recurrence were measured. RESULTS AND LIMITATIONS: In total, 65% of the patients had unilateral retroperitoneal lymph node metastases (RLNMs) on CT scans. Patients with unilateral RLNMs had a low risk of contralateral teratoma or cancer (1.6% for right- and 2.6% for left-sided NSGCT) or retroperitoneal recurrence (0% for right- and 4% for left-sided NSGCT). A weakness of the study is that the pathology specimen could not be fully designated to one specific area for some of the patients. CONCLUSIONS: Men with postchemotherapy residual disease of 10-49 mm and unilateral metastases on pre- and postchemotherapy CT scans have a low risk of contralateral disease and should be considered for a unilateral template resection. PATIENT SUMMARY: The surgeon can use computed tomography (CT) scans in deciding on the extent of lymph node dissection in patients with testicular cancer.
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Neoplasias Embrionárias de Células Germinativas , Neoplasias Retroperitoneais , Teratoma , Neoplasias Testiculares , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Masculino , Neoplasia Residual/cirurgia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Retroperitoneais/cirurgia , Suécia/epidemiologia , Teratoma/cirurgia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgiaRESUMO
OBJECTIVE: To explore the use of two-dimensional gel electrophoresis (2DE) for analysing the proteome of clinically relevant tissue samples such as biopsies from transurethral resections of the bladder (TURB), by generating a Ta proteome map, possibly identifying technical or biological artefacts, and searching for biological subgroups associated with clinical data. MATERIAL AND METHODS: Biopsies from 23 patients were homogenized and the protein content was separated by 2DE. The gels were silver stained and scanned, and the resulting pictures were analysed for similarities in the spot pattern. RESULTS: A majority of 18 patients displayed a consistent protein expression profile and a Ta proteome map was constructed by averaging the grey value of each pixel in all 18 pictures. Spot detection was performed on a project proteome map (based on all 23 samples) and resulted in 1583 detected spots. 416 of these which were positively detected in all 18 "Ta-map" samples. Three patients displayed a pattern with some marked alterations to the majority profile, possibly artefacts of yet unknown heredity. One patient revealed a protein pattern deemed to constitute a separate group, later revealed as a blinded control from a T4 tumour. Only one sample was sparse in protein spots, probably containing mostly blood owing to inadequate sampling. No biological subgroups associated with clinical data were identified. CONCLUSIONS: A Ta proteome map was successfully created from TURB samples. Deviating protein expression profiles were identified, indicating a future potential to reveal biologically relevant subgroups in this or other stages of urothelial cell carcinomas.
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Proteômica , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Eletroforese em Gel Bidimensional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Reports on perioperative complications after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for nonseminoma germ cell tumour (NSGCT) are from experienced single centres, with a lack of population-based studies. OBJECTIVE: To assess the complications of bilateral and unilateral PC-RPLND. DESIGN, SETTING, AND PARTICIPANTS: A prospective, population-based, observational multicentre study included all patients with NSGCT who underwent PC-RPLND in Norway and Sweden during 2007-2014. Of a total of 318 patients, 87 underwent bilateral PC-RPLND and 231 underwent unilateral PC-RPLND. The median follow-up was 6 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bilateral and unilateral PC-RPLND were compared for the outcomes of intra- and postoperative complications (graded by Clavien-Dindo) and retrograde ejaculation (with or without nerve-sparing surgery). Complications were reported as absolute counts and percentages. The χ2 test was used for comparisons. RESULTS AND LIMITATIONS: The incidence of intraoperative complications was higher for bilateral PC-RPLND than for unilateral PC-RPLND (14% vs 4.3%, p = 0.003), with ureteral injury as the most frequent reported complication (2% of the patients). Postoperative complications were more common after bilateral than after unilateral PC-RPLND (45% vs 25%, p = 0.001) with Clavien ≥3b reported in 8.3% and 2.2%, respectively (p = 0.009). Lymphatic leakage was the most common complication occurring in 11% of the patients. Retrograde ejaculation occurred more frequently after bilateral than after unilateral surgery (59% vs 32%, p < 0.001). Limitations of the study include reporting of retrograde ejaculation, which was based on a chart review. CONCLUSIONS: Intra- and postoperative complications including retrograde ejaculation are more frequent after bilateral PC-RPLND than after unilateral PC-RPLND. PATIENT SUMMARY: Lymph node dissection in patients with testicular cancer puts them at risk of complications. In this study, we present the complications after lymph node dissection.
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Complicações Intraoperatórias/epidemiologia , Excisão de Linfonodo/métodos , Neoplasias Embrionárias de Células Germinativas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Testiculares/cirurgia , Adulto , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Noruega , Estudos Prospectivos , Espaço Retroperitoneal , Suécia , Neoplasias Testiculares/tratamento farmacológico , Adulto JovemRESUMO
OBJECTIVE: To study the concordance between the Gleason scores of needle biopsies and radical prostatectomy (RP) specimens in a population-based registry, to clarify whether the concordance depends on the annual number of RP specimens assessed in the pathology unit, and to identify preoperative clinical factors that predict upgrading from a Gleason score of
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Próstata/patologia , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Idoso , Biópsia por Agulha , Métodos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Noruega/epidemiologia , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/cirurgiaRESUMO
OBJECTIVE: To assess the main characteristics of late relapsing malignant germ cell tumors (MGCTs). These tumors are rare and occur by definition 2 years or later after successful treatment. METHODS: We present relevant literature on relapsing MGCT in order to highlight the following issues: incidence, impact of initial treatment on the subsequent risk of late relapse, treatment, and survival. RESULTS: A pooled analysis of 5,880 patients with MGCT revealed late relapses in 119 of 3,704 (3.2%) and in 31 of 2,176 (1.4%) patients with non-seminoma and seminoma, respectively. The retroperitoneal space is the predominant site of relapse in both histological types. The initial treatment is important for the risk and localization of late relapses. Patients with single site teratoma are usually cured by surgery alone, whereas viable MGCT or teratoma with malignant transformation may require multimodal treatment with chemo- and/or radiotherapy as well as surgery. Surgery is the most important part in the treatment of late relapses. Salvage chemotherapy should, if feasible, be based on a representative biopsy. Five-year cancer-specific survival is above 50% in the recent large series and reaches 100% in case of single site teratoma. CONCLUSIONS: Treatment of late relapsing MGCT patients is challenging and should be performed in experienced centers only. Referral of late relapsing patients to high-volume institutions ensures the best chances of cure and enables multimodal treatment, and contributes to increased knowledge of tumor biology as well experience with the clinical course of these patients.
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Recidiva Local de Neoplasia/cirurgia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Retroperitoneais/cirurgia , Seminoma/cirurgia , Terapia Combinada , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/secundário , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/secundário , Seminoma/tratamento farmacológico , Seminoma/secundário , Teratoma/tratamento farmacológico , Teratoma/secundário , Teratoma/cirurgia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgiaRESUMO
BACKGROUND: The two major therapeutic options for early diagnosed prostate cancer are radical prostatectomy or radiation therapy. The National Program for Prostate Cancer in Norway conducted this study in order to document the use of treatment with curative intention in five geographical regions in Norway. MATERIAL AND METHODS: The study is based on data from the Cancer Registry of Norway on patients diagnosed with prostate cancer in 1998 and 2001. The departments of oncology have provided relevant information about radiation therapy. Treatment with curative intention is defined as radical prostatectomy or radiation therapy with > or = 64 Gy. RESULTS: About one third of all patients under the age of 75 years with recently diagnosed prostate cancer were treated with curative intention in 1998 and 2001 (1998: 28%, 2001: 33%); the total number increased from 440 in 1998 to 556 in 2001. There were marked variations between the geographical regions in the use of treatment with curative intention and in the use of radical prostatectomy versus radiation therapy. INTERPRETATION: The fact that no more than one third of the patients were treated with curative intention is probably due to uncertainty about the therapeutic benefit in relation to side effects. The regional variations probably reflect different opinions on the true effect of early diagnosis and treatment.
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Adenocarcinoma/terapia , Neoplasias da Próstata/terapia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Padrões de Prática Médica , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Dosagem Radioterapêutica , Sistema de Registros , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this article is to present the Swedish and Norwegian Testicular Cancer Group (SWENOTECA), with an emphasis on the history of SWENOTECA, organization, results and current status. MATERIALS AND METHODS: SWENOTECA was founded in 1981 as a binational organization open to hospitals in Sweden and Norway treating testicular cancer. It has since published treatment protocols for testicular cancer and prospectively registered patients with testicular cancer. Today, all hospitals in Norway and Sweden involved in the care of testicular cancer participate in SWENOTECA, and all patients with testicular cancer are prospectively registered in a population-based database. RESULTS: Nine protocols with standardized guidelines on the diagnosis, treatment and follow-up of testicular cancer have been published. In addition to the guidelines, several studies have been performed or initiated within the scope of SWENOTECA. The details are presented in this article. CONCLUSIONS: SWENOTECA has been a very fruitful binational collaboration and has thoughtfully evolved over time. The group's continuous work and dedication have provided an example for other national and international cancer networks. The binational implementation of standardized guidelines has resulted in excellent patient outcomes, regardless of place of residence. Although testicular cancer is a relatively rare disease, the population-based binational organization of SWENOTECA has made it possible to publish some of the largest studies in the field of testicular cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Comportamento Cooperativo , Cooperação Internacional , Neoplasias Embrionárias de Células Germinativas/terapia , Orquiectomia , Sistema de Registros , Neoplasias Testiculares/terapia , Bases de Dados Factuais , Humanos , Comunicação Interdisciplinar , Excisão de Linfonodo , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/patologia , Noruega , Suécia , Neoplasias Testiculares/patologiaRESUMO
BACKGROUND: Characterising responders to neoadjuvant chemotherapy (NAC) is important to minimise overtreatment and the unnecessary delay of definitive treatment of urothelial urinary bladder cancer. OBJECTIVE: To assess the effect of NAC on tumour downstaging and overall survival. DESIGN, SETTING, AND PARTICIPANTS: A total of 449 patients from the randomised prospective Nordic Cystectomy Trials 1 and 2 were analysed retrospectively. Eligible patients were defined as T2-T4aNXM0 preoperatively and pT0-pT4aN0-N+M0 postoperatively. The median follow-up time was 5 yr. INTERVENTION: The experimental arm consisted of cisplatin-based NAC; the control arm consisted of cystectomy only. MEASUREMENTS: The primary outcome was tumour downstaging defined as pathologic TNM less than clinical TNM. Different downstaging thresholds were applied: complete downstaging (CD) (pT0N0), noninvasive downstaging (NID) (pT0/pTis/pTaN0), and organ confinement (OC) (≤ pT3aN0). Downstaging rates and nodal status were compared between the study arms using the chi-square test. Secondary outcome was overall survival (OS) stratified by treatment arm, downstaging categories, and clinical stages, analysed by the Kaplan-Meier method. The following covariates were tested as prognostic factors in univariate and multivariate analyses using the Cox regression method: age, sex, clinical stage, pN status, NAC, CD, NID, and OC. RESULTS AND LIMITATIONS: Downstaging rates increased significantly in the NAC arm independent of the downstaging threshold. The impact was more prominent in clinical T3 tumours, with a near threefold increase in CD tumours. The combination of CD and NAC showed an absolute risk reduction of 31.1% in OS at 5 yr compared with CD controls. The combination of NAC and CD revealed a hazard ratio of 0.32 compared with 1.0 for the combination of no NAC and no CD. Limitations were the retrospective approach and uncertain clinical TNM staging. CONCLUSIONS: Survival benefits of NAC are reflected in downstaging of the primary tumour. Chemo-induced downstaging might be a potential surrogate marker for OS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistectomia , Terapia Neoadjuvante , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Distribuição de Qui-Quadrado , Cisplatino/administração & dosagem , Cistectomia/efeitos adversos , Cistectomia/mortalidade , Doxorrubicina/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Músculo Liso/patologia , Músculo Liso/cirurgia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Países Escandinavos e Nórdicos , Fatores de Tempo , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Urotélio/cirurgiaRESUMO
PURPOSE: From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. METHODS: Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for α-fetoprotein (AFP) of ≤ 7 days and/or for ß-human chorionic gonadotropin (ß-HCG) of ≤ 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. RESULTS: Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. CONCLUSION: With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Bleomicina/uso terapêutico , Cisplatino/uso terapêutico , Esquema de Medicação , Etoposídeo/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Noruega , Vigilância da População , Prognóstico , Suécia , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologiaRESUMO
Trends in incidence and mortality rates of prostate cancer were analyzed using data from the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden. Joinpoint regression models were used to quantify temporal trends for the period from 1980 to 2004. Incidence rates were increasing and similar in the Nordic countries during the 1980s. Around 1990, a more rapid incidence increase began in all Nordic countries except Denmark, where an increase was seen 5 years later. In 2001, incidence rates in Denmark were half of those seen in the other Nordic countries, but mortality rates varied only marginally among countries. Mean annual declines in prostate cancer mortality of 1.9% (95% CI = 0.4% to 3.3%) and 1.8% (95% CI = 0.5% to 3.0%) were observed from 1996 to 2004 in Finland and Norway, respectively. During the same period, mortality rates leveled off in Iceland and Sweden but continued to increase in Denmark. The rapid increase in incidence during the early 1990s coincided with the introduction of the prostate-specific antigen (PSA) test and conveys little information about the occurrence of potentially lethal disease. Mortality rates, however, have recently stabilized or declined in countries where PSA testing and curative treatment have been commonly practiced since the late 1980s. Although other explanatory factors may be in operation, these trends are consistent with a moderate effect of increased curative treatment of early diagnosed prostate cancer and improved treatment of more advanced disease.