RESUMEN
BACKGROUND: Little is known regarding sperm production following adjuvant treatment in testicular cancer (TC) clinical stage I (CS I) patients. PATIENTS AND METHODS: A total of 182 TC patients aged 18-50 years were prospectively included during 2001-2006 at any given time within 5 years of orchiectomy. Semen samples were delivered postorchiectomy but before further treatment, 6, 12, 24, 36 and 60 months (T0-T60) after completed therapy. Total sperm number (TSN) and sperm concentration (SC) were used as measurements of testicular function. Four groups according to treatment modality were identified; Radiotherapy; To a total dose of 25.2 Gy to the infradiaphragmal paraaortic and ipsilateral iliac lymph nodes (RT, N = 70), one cycle of adjuvant BEP (bleomycin, etoposide, cisplatin, 5 day regimen) (BEP, N = 62), one cycle of adjuvant carboplatin AUC 7 (Carbo, N = 22), and patients managed by surveillance (SURV, N = 28). RESULTS: In the cross-sectional analysis, a significant but transient drop in mean TSN and mean SC (T0-T60) was seen at T6 after radiotherapy. Apart from a significant increase in mean SC at T12 compared with baseline, no significant differences were observed in the other treatment groups. In 119 patients delivering 3 or more samples, values in TSN and SC were rather stable over time. Azoospermic patients (N = 11) were observed in most treatment groups except for in the BEP group. During follow-up, one azoospermic patient belonging to the Carbo group became normospermic. CONCLUSIONS: No clinically significant long-term effect on TSN or SC associated with adjuvant treatment in TC CSI patients was found. However, as patients may have low sperm counts before orchiectomy as well as after adjuvant treatment, we offer sperm banking before orchiectomy as assisted reproductive measures may be necessary regardless of treatment given.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia Adyuvante/efectos adversos , Orquiectomía , Recuento de Espermatozoides , Neoplasias Testiculares/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Estudios Transversales , Preservación de la Fertilidad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Bancos de Esperma , Espermatozoides/efectos de los fármacos , Espermatozoides/efectos de la radiación , Suecia , Neoplasias Testiculares/patología , Testículo/efectos de los fármacos , Testículo/patología , Testículo/efectos de la radiación , Testículo/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
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Oncología Médica/normas , Recurrencia Local de Neoplasia/prevención & control , Neoplasias de Células Germinales y Embrionarias/terapia , Guías de Práctica Clínica como Asunto , Neoplasias Testiculares/terapia , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Supervivientes de Cáncer/psicología , Quimioradioterapia Adyuvante/métodos , Quimioradioterapia Adyuvante/normas , Conferencias de Consenso como Asunto , Europa (Continente) , Humanos , Masculino , Oncología Médica/métodos , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/normas , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/patología , Orquiectomía/psicología , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Pronóstico , Calidad de Vida , Factores de Riesgo , Terapia Recuperativa/métodos , Terapia Recuperativa/normas , Sociedades Médicas/normas , Supervivencia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , Testículo/diagnóstico por imagen , Testículo/patología , Testículo/cirugíaRESUMEN
BACKGROUND: The purpose of the protocol was to reduce the treatment burden in clinical stage I (CSI) seminoma by offering risk-adapted treatment. The protocol aimed to prospectively validate the proposed risk factors for relapse, stromal invasion of the rete testis and tumor diameter >4 cm, and to evaluate the efficacy of one course of adjuvant carboplatin. PATIENTS AND METHODS: From 2007 to 2010, 897 patients were included in a prospective, population-based, risk-adapted treatment protocol implementing one course of adjuvant carboplatin AUC7 (n = 469) or surveillance (n = 422). In addition, results from 221 patients receiving carboplatin between 2004 and 2007 are reported. RESULTS: At a median follow-up of 5.6 years, 69 relapses have occurred. Stromal invasion of the rete testis [hazard ratio (HR) 1.9, P = 0.011] and tumor diameter >4 cm (HR 2.7, P < 0.001) were identified as risk factors predicting relapse. In patients without risk factors, the relapse rate (RR) was 4.0% for patients managed by surveillance and 2.2% in patients receiving adjuvant carboplatin. In patients with one or two risk factors, the RR was 15.5% in patients managed by surveillance and 9.3% in patients receiving adjuvant carboplatin. We found no increased RR in patients receiving carboplatin <7 × AUC compared with that in patients receiving ≥7 × AUC. CONCLUSION: Stromal invasion in the rete testis and tumor diameter >4 cm are risk factors for relapse in CSI seminoma. Patients without risk factors have a low RR and adjuvant therapy is not justified in these patients. The efficacy of adjuvant carboplatin is relatively low and there is need to explore more effective adjuvant treatment options in patients with high-risk seminoma. The data do not support the concept of a steep dose response for adjuvant carboplatin.
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Carboplatino/administración & dosificación , Quimioterapia Adyuvante/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Seminoma/tratamiento farmacológico , Adulto , Anciano , Carboplatino/efectos adversos , Terapia Combinada/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Noruega/epidemiología , Factores de Riesgo , Seminoma/epidemiología , Seminoma/patología , Suecia/epidemiología , Resultado del TratamientoRESUMEN
Testicular cancer (TC) is the most common neoplasm in males aged 15-40 years. The majority of patients have no evidence of metastases at diagnosis and thus have clinical stage I (CSI) disease [Oldenburg J, Fossa SD, Nuver J et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi125-vi132; de Wit R, Fizazi K. Controversies in the management of clinical stage I testis cancer. J Clin Oncol 2006; 24: 5482-5492.]. Management of CSI TC is controversial and options include surveillance and active treatment. Different forms of adjuvant therapy exist, including either one or two cycles of carboplatin chemotherapy or radiotherapy for seminoma and either one or two cycles of cisplatin-based chemotherapy or retroperitoneal lymph node dissection for non-seminoma. Long-term disease-specific survival is â¼99% with any of these approaches, including surveillance. While surveillance allows most patients to avoid additional treatment, adjuvant therapy markedly lowers the relapse rate. Weighing the net benefits of surveillance against those of adjuvant treatment depends on prioritizing competing aims such as avoiding unnecessary treatment, avoiding more burdensome treatment with salvage chemotherapy and minimizing the anxiety, stress and life disruption associated with relapse. Unbiased information about the advantages and disadvantages of surveillance and adjuvant treatment is a prerequisite for informed consent by the patient. In a clinical scenario like CSI TC, where different disease-management options produce indistinguishable long-term survival rates, patient values, priorities and preferences should be taken into account. In this review, we provide an overview about risk factors for relapse, potential benefits and harms of adjuvant chemotherapy and active surveillance and a rationale for involving patients in individualized decision making about their treatment rather than adopting a uniform recommendation for all.
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Antineoplásicos/uso terapéutico , Técnicas de Apoyo para la Decisión , Neoplasias de Células Germinales y Embrionarias/terapia , Participación del Paciente , Autonomía Personal , Seminoma/terapia , Neoplasias Testiculares/terapia , Espera Vigilante , Adolescente , Adulto , Antineoplásicos/efectos adversos , Quimioterapia Adyuvante , Conducta de Elección , Progresión de la Enfermedad , Humanos , Masculino , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/patología , Orquiectomía/efectos adversos , Selección de Paciente , Valor Predictivo de las Pruebas , Radioterapia Adyuvante , Factores de Riesgo , Seminoma/patología , Neoplasias Testiculares/patología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Although clinical stage I (CS I) testicular cancer is highly curable, the optimal management is controversial. The aims of the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) studies for CS I non-seminoma (NS) and seminoma (S) have been to reduce treatment intensity while maintaining high survival rates, reduce the number of patients needing salvage treatment and implement patient autonomy with regard to adjuvant treatment. During 1998-2010 NS CSI patients with lymphovascular invasion (LVI) of the primary tumor (high risk) were recommended bleomycin, etoposide, cisplatin (BEP) × 1. During 2000-2006 S CS I patients had the option to choose surveillance or adjuvant radiotherapy (AR). In 2004, carboplatin × 1 (AUC7) was added as a third treatment option. In 2007 a new risk-adapted treatment protocol for S CS I was initiated. Patients with two risk factors (tumor size > 4 cm, tumor growth in the rete testis) were recommended carboplatin × 1 and patients with 0-1 risk factor were recommended surveillance. All patients were provided with oral and written information of possible management options and could choose the other alternative. The relapse rate for NS CS I with BEP × 1 was 3.2% for high risk, and 1.6% for low-risk patients. Five-year cause-specific survival was 100%. For S CS I-patients treated before 2007, 14.3% on surveillance relapsed, 3.9% after carboplatin, and 0.8% after AR. Five-year cause-specific survival was 99.9%. For S CS I-patients treated from 2007, a relapse rate <3% was confirmed for patients without risk factors. SWENOTECA considers BEP × 1 standard adjuvant treatment in NS CS I high-risk patients. Low-risk patients should have the opportunity to receive BEP × 1 following thorough information regarding pros and cons. For S CS I patients without risk factors, adjuvant treatment is not necessary. For patients with risk factors, patient autonomy should be respected.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias Testiculares/patología , Neoplasias Testiculares/terapia , Espera Vigilante , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Humanos , Masculino , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/mortalidad , Noruega/epidemiología , Selección de Paciente , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Suecia/epidemiología , Neoplasias Testiculares/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Carga TumoralRESUMEN
BACKGROUND: SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. PATIENTS AND METHODS: In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. RESULTS: At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. CONCLUSIONS: The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.
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Bleomicina/administración & dosificación , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Neoplasias Testiculares/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/patologíaRESUMEN
Azoospermia is a serious potential side effect following treatment for testicular cancer (TC). Our purpose was to examine possible predictors of long-term azoospermia in TC survivors. Ejaculates and blood samples were obtained from 217 patients at post-orchidectomy but before further treatment (T0 ) and/or at one or more of the time points 6, 12, 24, 36-60 months after treatment (T6 , T12 , T24 , T36-60 ). All patients delivered ejaculates at T36-60 , of which 117 also had confirmed presence of spermatozoa in the ejaculate at T0 , enabling longitudinal analyses. Types of therapy, cryptorchidism and Inhibin B before and after treatment were evaluated in relation to risk of azoospermia at T36 . Inhibin B levels at T6 , T12 and T24 were predictors of azoospermia at T36 with cut-off levels at 49.7, 55.9 and 97.8 ng/L respectively (sensitivity 100%, specificity 57-78%). The frequency of azoospermia in all patients at T36-60 was 7.8% (95% CI 4.9-12%). As compared to surveillance patients, only those receiving >4 cycles of chemotherapy or ≥4 cycles of chemotherapy + radiotherapy (RT) had increased risk of long-term azoospermia (63% vs. 4.4% in the surveillance group; p = 0.0018). In conclusion, all patients with sperm production at post-orchidectomy but before further treatment and Inhibin B >56 ng/L 12 months after treatment had sperm production 3 years post-treatment. Eight per cent of TC survivors had azoospermia 3-5 years post-treatment, with highest risk in those receiving >4 cycles of chemotherapy or ≥4 cycles of chemotherapy in combination with RT.
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Azoospermia/sangre , Azoospermia/epidemiología , Inhibinas/sangre , Neoplasias Testiculares , Adolescente , Adulto , Carboplatino/efectos adversos , Carboplatino/uso terapéutico , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Criptorquidismo/complicaciones , Etopósido/efectos adversos , Etopósido/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Orquiectomía/efectos adversos , Espermatozoides , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/radioterapia , Neoplasias Testiculares/cirugía , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , Adulto JovenRESUMEN
In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, â¼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
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Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/terapia , Europa (Continente) , Estudios de Seguimiento , Humanos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/clasificación , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Tasa de SupervivenciaRESUMEN
Contexto: La Asociación Europea de Urología (EAU) estableció la guía clínica para el diagnóstico, la terapia y el seguimiento del cáncer de testículo. Objetivo: Este artículo es una versión abreviada de la guía clínica del cáncer de testículo de la EAU y resume las conclusiones principales de la guía sobre el tratamiento del cáncer testicular. Obtención de evidencia: Un equipo multidisciplinar de guías clínicas compiló esta guía. Se llevó a cabo una revisión sistemática mediante Medline y Embase, tomando también datos Cochrane e información del European Germ Cell Cancer Consensus Group. Un grupo de expertos valoró las referencias y se asignó un nivel de evidencia y grado de recomendación. Resultados: La bibliografía, especialmente con respecto al seguimiento a más largo plazo, es escasa y los resultados de varios ensayos en curso están a la espera. La elección del centro de tratamiento es de suma importancia y el tratamiento en centros de referencia en ensayos clínicos, especialmente en tumores de células germinativas no seminomatosos, proporciona mejores resultados. En los pacientes con seminoma en estadio clínico I, en base a información publicada recientemente sobre toxicidad a largo plazo, ya no se recomienda la radioterapia adyuvante como tratamiento adyuvante de primera línea. Se recomienda la clasificación TNM del 2009. Conclusiones: Esta guía contiene información para el tratamiento normalizado de los pacientes con cáncer de testículo en base a las apreciaciones científicas más recientes. Las tasas de curación son generalmente excelentes, pero como el cáncer de testículo afecta principalmente a hombres en su tercera o cuarta década de vida, los efectos del tratamiento en la fertilidad requieren ayuda psicológica para los pacientes. Además, el tratamiento debe ser individualizado teniendo en cuenta las circunstancias individuales y las preferencias del paciente. Mensaje a principal: Aunque el cáncer de testículo presenta unas tasas de curación excelentes, la elección del centro de tratamiento es de capital importancia. Los centros expertos logran mejores resultados tanto para el cáncer testicular en estadio inicial (tasas de recidiva más bajas) como para la supervivencia global (estadios más altos en los ensayos clínicos). En los pacientes con seminoma en estadio clínico I, ya no se recomienda la radioterapia adyuvante como tratamiento adyuvante de primera línea (AU)
Context: On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established. Objective: This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer. Evidence acquisition: Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned. Results: There is a paucity of literature especially regarding longer term follow-up, and results from a number of on going trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor prognosis non seminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended. Conclusions: These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account. Take Home Message: Although testicular cancer has excellent cure rates, the choice of treatment centre is of the utmost importance. Expert centres achieve better results for both early stage testicular cancer (lower relapse rates) and overall survival (higher stages within clinical trials). For patients with clinical stage I seminoma, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment (AU)
Asunto(s)
Humanos , Masculino , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Pautas de la Práctica en Medicina , Estudios de Seguimiento , Evaluación de Resultados de Intervenciones Terapéuticas , Seminoma/patología , Terapia NeoadyuvanteRESUMEN
BACKGROUND: 2-¹8fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) has been recommended in international guidelines in the evaluation of postchemotherapy seminoma residuals. Our trial was designed to validate these recommendations in a larger group of patients. PATIENTS AND METHODS: FDG-PET studies in patients with metastatic seminoma and residual masses after platinum-containing chemotherapy were correlated with either the histology of the resected lesion(s) or the clinical outcome. RESULTS: One hundred and seventy seven FDG-PET results were contributed. Of 127 eligible PET studies, 69% were true negative, 11% true positive, 6% false negative, and 15% false positive. We compared PET scans carried out before and after a cut-off level of 6 weeks after the end of the last chemotherapy cycle. PET sensitivity, specificity, negative predictive value (NPV), and positive predictive value were 50%, 77%, 91%, and 25%, respectively, before the cut-off and 82%, 90%, 95%, and 69% after the cut-off. PET accuracy significantly improved from 73% before to 88% after the cut-off (P=0.032). CONCLUSION: Our study confirms the high specificity, sensitivity, and NPV of FDG-PET for evaluating postchemotherapy seminoma residuals. When carried out at an adequate time point, FDG-PET remains a valuable tool for clinical decision-making in this clinical setting and spares patients unnecessary therapy.
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Glucosa-6-Fosfato/análogos & derivados , Tomografía de Emisión de Positrones , Radiofármacos , Seminoma/diagnóstico por imagen , Neoplasias Testiculares/diagnóstico por imagen , Humanos , Masculino , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
CONTEXT: On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established. OBJECTIVE: This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer. EVIDENCE ACQUISITION: Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned. RESULTS: There is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended. CONCLUSIONS: These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account. TAKE HOME MESSAGE: Although testicular cancer has excellent cure rates, the choice of treatment centre is of the utmost importance. Expert centres achieve better results for both early stage testicular cancer (lower relapse rates) and overall survival (higher stages within clinical trials). For patients with clinical stage I seminoma, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment.
Asunto(s)
Neoplasias Testiculares/terapia , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Instituciones Oncológicas , Quimioterapia Adyuvante , Terapia Combinada , Diagnóstico por Imagen/métodos , Manejo de la Enfermedad , Medicina Basada en la Evidencia , Humanos , Escisión del Ganglio Linfático , Masculino , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/cirugía , Orquiectomía , Tratamientos Conservadores del Órgano , Pronóstico , Radioterapia Adyuvante/efectos adversos , Terapia Recuperativa , Tumores de los Cordones Sexuales y Estroma de las Gónadas/tratamiento farmacológico , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/cirugía , Sociedades Médicas/normas , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: To offer minimized risk-adapted adjuvant treatment on a community and nationwide basis for patients with clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT). The aim was to reduce the risk of relapse and thereby reducing the need of later salvage chemotherapy while maintaining a high cure rate. PATIENTS AND METHODS: From July 1995 to January 1998, a total of 232 Swedish and Norwegian patients were treated for CS1 NSGCT. All were eligible for inclusion into one of two community-based multicenter Swedish and Norwegian Testicular Cancer Project (SWENOTECA) III studies. One study was a prospective randomized study for patients without vascular invasion in the testicular tumor (VASC-), evaluating the effect of one adjuvant course of cisplatin, vinblastine and bleomycin (CVB) compared with surveillance. The second study was a prospective study evaluating the effect of two adjuvant courses of CVB for VASC+ patients. RESULTS: Due to slow accrual and emerging data on toxicity of CVB, the studies were prematurely closed for inclusion in 1998. Of the 232 CS1 patients treated during the study period, only 97 were included in the studies. As all remaining patients were managed according to the SWENOTECA III protocol, although not randomized, the data were pooled. At a median follow-up of 10.1 years, there have been 24 relapses. While one course of CVB to VASC- patients had limited effect on the relapse rate, two courses of adjuvant CVB reduced the relapse rate among VASC+ patients by >90%. Toxicity was high in patients administered adjuvant CVB as 24% of patients experienced grade 3 or 4 obstipation/ileus and 23% grade 3 or 4 infection. CONCLUSIONS: There was no statistical difference in relapse rate between one course of adjuvant CVB and surveillance for VASC- NSGCT patients. Two courses of adjuvant CVB for VASC+ NSGCT patients reduced the relapse rate with >90% in comparison to the surveillance group. Toxicity was unacceptably high for all patients receiving CVB. Adjuvant CVB chemotherapy has no place in the treatment of CS1 NSGCT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/prevención & control , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Vasculares/tratamiento farmacológico , Adulto , Bleomicina/administración & dosificación , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Estudios de Seguimiento , Humanos , Masculino , Invasividad Neoplásica , Recurrencia Local de Neoplasia/diagnóstico , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/patología , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Neoplasias Testiculares/patología , Factores de Tiempo , Resultado del Tratamiento , Neoplasias Vasculares/patología , Vinblastina/administración & dosificaciónRESUMEN
BACKGROUND: Large, prospective, randomized trials with long term follow-up are required to obtain an unbiased evaluation of the significance of resection margins in patients with cutaneous melanoma. METHODS: The Swedish Melanoma Study Group performed a prospective, randomized, multicenter study of patients with primary melanoma located on trunk or extremities and with a tumor thickness > 0.8 mm and = 2 mm. Patients were allocated randomly to a 2-cm excision margin or a 5-cm excision margin. In total, 989 patients were recruited during the period 1982-1991. The median follow-up was 11 years (range, 7-17 years) for estimation of survival and 8 years (range, 0-17 years) for evaluation of recurrent disease. RESULTS: The crude rate of local recurrence, defined as a recurrence in the scar or transplant, was < 1% (8 of 989 patients). Twenty percent of the patients (194 of 989 patients) experienced any disease recurrence, and 15% (146 of 989 patients) died of melanoma. There were no statistically significant differences between the two treatment arms. In a multivariate Cox analysis with patients allocated to wide excision as the reference group, the estimated relative hazards for overall survival and recurrence free survival among those allocated to a 2-cm resection margin were 0.96 (95% confidence interval, 0.75-1.24), and 1.02 (95% confidence interval, 0.80-1.30), respectively. CONCLUSIONS: In this long term follow-up study, local recurrences were found to be rare among patients with tumors > 0.8 mm thick and = 2.0 mm thick. No difference in recurrence rate or survival between the two treatment groups was found. Patients in this category can be treated with a resection margin of 2 cm as safely as with a resection margin of 5 cm.
Asunto(s)
Melanoma/cirugía , Recurrencia Local de Neoplasia , Neoplasias Cutáneas/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasia Residual , Neoplasias Cutáneas/patología , Análisis de SupervivenciaRESUMEN
BACKGROUND: The rise in melanoma-related mortality in Sweden has been less pronounced than the increase in incidence. Interventional activities aimed at early detection may have contributed to this discrepancy. METHODS: Individuals with malignant melanoma as the underlying cause of death between 1970 and 1996 (n = 7177) formed the basis of this study. Annual age-standardized mortality rates were calculated using the direct method of standardization with the Swedish population of 1970 as reference. Temporal trends in the standardized rates were evaluated using a log-linear model. The effects of age, period, and cohort on the mortality trends were estimated using a Poisson regression model. RESULTS: Since the mid-1980s, melanoma-related mortality in Sweden has leveled off, with no further increase during the last 10-15 years. The contribution to the mortality from noncutaneous melanoma was proportionally stable (20-25%) during the studied period. In females, a significant decrease in mortality from cutaneous melanoma was shown for the period of 1987-1996 with an estimated annual decrease of -2.3% (95% confidence interval: -4.3 to -0.3). This trend appeared to be more pronounced in the Stockholm-Gotland region. The observed trends were best explained with the age-period model in both genders. CONCLUSIONS: Melanoma-related mortality in Sweden has leveled off since the mid-1980s. During the period 1987-1996, a statistically significant downward trend was observed for females. This trend coincides with increased preventional activities.
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Melanoma/mortalidad , Neoplasias Cutáneas/mortalidad , Adulto , Factores de Edad , Anciano , Femenino , Educación en Salud , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/prevención & control , Persona de Mediana Edad , Mortalidad/tendencias , Análisis Multivariante , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/prevención & control , Análisis de Supervivencia , Suecia/epidemiologíaRESUMEN
The objective of this population-based study was to assess metastatic pathways and outcomes vs. selected clinical and histopathologic features of the primary tumor in patients with recurrent cutaneous malignant melanoma. At a median follow-up time of 11 years, 569/2493 patients with recurrence were identified. We demonstrated a 5-year survival rate of 82% and 30% among those with a primary local or regional recurrence, respectively. Patients with primary distant skin, distant lymph node, or pulmonary metastases had a significantly better survival compared with those with CNS, bone, visceral, liver, or multiple sites of first distant metastases. The metastatic pathways were similar with regard to histogenetic type, primary tumor thickness, Clark's level of invasion, and primary tumor ulceration. Different histogenetic types, as assessed by light microscopy, imply different risks of recurrence. However, once the recurrence is manifest, the metastatic pathways are uniform, as well as prognosis, and survival.
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Melanoma/patología , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Sistema de Registros , Neoplasias Cutáneas/patología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Pronóstico , Análisis de SupervivenciaRESUMEN
The objectives of this population-based study were to assess putative prognostic factors for central nervous system (CNS) metastases among patients with cutaneous malignant melanoma, to assess the cumulative risk of CNS metastases in different subsets of patients with recurrent disease, and to describe patient outcome. At a median follow-up of 11 years, 201/2516 patients with melanoma had developed CNS metastases, corresponding to a cumulative risk at 5 years of 7%. In 41 of these 201 patients the CNS metastases were recorded as the first site of recurrence. In a Cox's multivariate model, primary tumor thickness and ulceration in stage I patients were independent risk factors. The cumulative rates of incidence of CNS metastases 5 years after local or regional recurrence as first event were 5 and 42%, respectively. These results may help to form an individually based risk assessment, which might be of value for melanoma patients in certain occupations.
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Neoplasias del Sistema Nervioso Central/secundario , Melanoma/secundario , Neoplasias Cutáneas/patología , Adulto , Anciano , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/epidemiología , Neoplasias del Sistema Nervioso Central/mortalidad , Femenino , Humanos , Incidencia , Masculino , Melanoma/diagnóstico , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Neoplasias Cutáneas/diagnóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The definition of local recurrence of cutaneous malignant melanoma varies. The outcomes of patients with a local recurrence reported in the literature also vary, but the appearance of a local recurrence has generally been considered a negative prognostic sign. Few studies have been population-based thus far. METHODS: During the period 1976-1997, 3706 patients with cutaneous malignant melanoma (including 575 patients with melanoma in situ) were registered in a population-based regional cancer registry. Local recurrence was defined as a recurrence within the scar or transplant with no signs of regional or distant spread of the disease. Prognostic factors were investigated using univariate and multivariate analytic techniques. The prognostic importance of a local recurrence in terms of survival was analyzed using the Cox proportional hazards regression model, with local recurrence as a time-dependent covariate. RESULTS: Local recurrence as a first event was rare (occurring in 48 of 3706 patients, or 1.3%). Twenty-eight percent (11 of 39) of the patients with local recurrence of invasive primary melanoma developed distant metastases and subsequently died. Only ulceration had prognostic significance in univariate analysis. A Cox analysis, with melanoma death as the endpoint and local recurrence as a time-dependent covariate, demonstrated a relative risk of 1.3 associated with local recurrence; however, this was not statistically significant (confidence interval, 0.7-2.3). CONCLUSIONS: In this population-based study, local recurrence was a rare event. The outcomes after diagnosis were relatively favorable. The results did not indicate a major detrimental effect on survival from the local recurrence per se.
Asunto(s)
Melanoma/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Melanoma/epidemiología , Melanoma/cirugía , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Modelos de Riesgos Proporcionales , Sistema de Registros , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/cirugíaRESUMEN
The authors studied prognostic factors in 77 patients with primary cystosarcoma phyllodes (CSP) of the breast. Median patient age was 50 years of age, and the median follow-up time was 8 years. Sixteen patients (21%) had distant metastases and subsequently died of CSP. Clinical variables such as age, symptom duration, clinical tumor size, and type of surgery were not of prognostic value. Local recurrence was more common among patients treated with breast-conserving surgery than among those treated with mastectomy. However, there was no significant difference between these two subgroups in terms of distant metastasis-free survival or overall survival. The prognostic significance of several histopathologic parameters was also assessed, e.g., stromal cellularity, stromal cellular atypism, mitotic activity, atypic mitoses, stromal overgrowth, tumor contour, tumor necrosis, and heterologous stromal elements. In a multivariate Cox analysis, the only features that were found to be independent prognostic factors were tumor necrosis (P less than 0.05) and presence of stromal elements other than fibromyxoid tissue (P less than 0.01). In summary, additional studies of prognostic factors in CSP are warranted because of the conflicting results in published reports.