Search

Cancer Core Europe brings together the expertise, resources, and interests of seven leading cancer institutes committed to leveraging collective innovation and collaboration in precision oncology. Through targeted efforts addressing key medical challenges in cancer and partnerships with multiple stakeholders, the consortium seeks to advance cancer research and enhance equitable patient care., (©2024 American Association for Cancer Research.)

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia., Competing Interests: Disclosure RK declares institutional payments from Pfizer, MSD, BMS, Eisai, Amgen, Astellas, J&J, Novartis and Merck and support for meeting attendance or travel from Pfizer, MSD, BMS, Eisai, Amgen, Astellas, J&J, Novartis and Merck. EC declares an institutional grant from Janssen, consulting fees from Astellas, AstraZeneca, Bayer, MSD and Pfizer, fees and honoraria for lectures, presentations from Astellas, AstraZeneca, Bayer, Janssen, MSD and Pfizer and support for attending meetings or travel from AstraZeneca and Janssen. AW declares personal fees from MS, MSD, Pfizer, Eisai and IPSEN and participation on a data safety monitoring or advisory board for BMS, MSD, Pfizer, Eisai and IPSEN. KF declares institutional honoraria for participation in advisory boards and talks for: Amgen, Astellas, Astrazeneca, Bayer, Clovis, Janssen, MSD, Novartis/AAA, Pfizer and Sanofi, and personal honoraria for participation to advisory boards for CureVac and Orion. MLKC declares payments or honoraria from ImmunoScape, IQVIA, Telix, Atsellas, AstraZeneca, Bayer, Illumina, Janssen, MSD, Pfizer and Varian, participation on a data safety monitoring or advisory board for AstraZeneca, Astellas, Bayer Pharma, Illumina, Janssen Pharma, MSD Oncology and Varian, a grant from Ferring, stock option in Digital Life Line, a role with the F1000—Head and Neck Cancer Section, Singapore Society of Oncology and Head Neck Caner International Group and other financial interests in Medlever and Varian. HM declares personal fees from CIPLA, Novartis, AstraZeneca, Roche, Eli Lilly, Merck, Pfizer, MSD, CADILA, Bard India and Somex Research. YM declares payments or honoraria from BMS, MSD and Takeda, participation on an advisory board for Chugai Pharmaceutical and Takeda and local PI, institutional, financial interest from MSD. JLL declares institutional grants or contracts from Pfizer, Novartis BMS, Janssen, MSD, Roche/Genetech, AstraZeneca/MedImmune, Seagen Astellas, Bayer, Schering Pharma, Lilly and Merck and participation on a data safety monitoring or advisory board from Pfizer Korea, Astella Korea, BMS, Merck, MSD, AstraZeneca, stocks or stock options from Myovant Sciences, Amgen, Johnson and Johnson and Merck. YSP declares honoraria and consulting fees from MSD, Roche, Merck, Ipsen, BMS/ONO, Novartis, Pfizer, Astellas, Janssen and GSK and support for attending meetings and/or travel from Ipsen, BMS/ONO, Novartis, Pfizer, Astellas and Janssen. MS declares research grants from Johnson and Johnson, payments or honoraria from Johnson and Johnson, AstraZeneca, Amgen and CIPLA, support for meeting attendance from Astellas, fees for participation in data monitoring or advisory boards from Johnson and Johnson, Amgen and AstraZeneca and receipt of equipment/materials for a compassionate programme for drugs/drug samples from Johnson and Johnson, AstraZeneca and Astellas. HJL declares participation on a data safety monitoring or advisory board for Astellas Korea. HK declares payments or honoraria from Astellas, AstraZeneca, Janssen, Sanofi and Takeda and payment for expert testimony and participation in an advisory board for Janssen. KP declares institutional research funding from Dr Reddy’s Laboratories Inc., Fresenius Kabi India Pvt. Ltd., Alkem Laboratories, Natco Pharma Ltd., BDR Pharmaceuticals Intl. Pvt. Ltd and Roche Holding AG and a role with ICON and the FHNO. GC declares institutional grants from Merck, consulting fees from BMS, Roche, Pfizer, MSD, AstraZeneca, Daichii Sankyo, Lilly, Novartis Ellipsis and Seagen, payment or honoraria from Pfizer and Lilly and support for attending meetings from Roche and Pfizer. EP declares grants and contracts form the National Cancer Centre research fund and Singapore Health Duke-NUS Oncology Academic Clinical Programme Sarcoma Research Fund award and Vice Presidency of the SSO. SPC declares consulting fees from BMS, AstraZeneca, Roche and Eisai and payment or honoraria from BMS, AstraZeneca, Roche, MSD, Eisai and Servier. SP declares fees for consultancy/advisory roles from AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, BMS, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Foundation Medicine, Illumina, Imedex, Incyte, Janssen, Medscape, MSD, Merck Serono, Merrimack, Novartis, Pharma Mar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, Roche/Genentech, RTP, Sanofi, Seattle Genetics and Takeda, speaker roles for AstraZeneca, Boehringer Ingelheim, BMS, ecancer, Eli Lilly, Illumina, Imedex, Medscape, MSD, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda and the receipt of grants/research support: (Sub) investigator in trials (institutional financial support for trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, BMS, Clovis, GSK, Illumina, Lilly, MSD, Merck Serono, Mirati, Novartis, Pfizer, Phosplatin Therapeutics and Roche/Genentech. TY declares institutional grants or contracts from Taiho Pharmaceuticals, Sumitomo Dainippon, Ono Pharmaceuticals, Chugai Pharmaceuticals, Amgen K.K., Parexel International, MSD K.K., Daiichi Sankyo and Sanofi. All other authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure CP has reported honoraria from Bayer, Janssen and Advanced Accelerator Applications (AAA) and research grants from Bayer; EC has reported honoraria from Astellas, AstraZeneca, Bayer, Janssen and Pfizer and research grants from AstraZeneca, Bayer and Janssen; KF has reported participation to advisory boards/honoraria for Astellas, AAA, Bayer, Clovis, Curevac, Incyte, Janssen, Merck Sharp & Dohme, Orion, Sanofi; AH has reported paid consultancy for Amgen, Astellas, Ferring, Ipsen, Jansen, Pfizer, Sanofi, Takeda and has received research grants from Astellas and Sanofi; PO has reported institutional honoraria from Janssen, Bayer, Ferring Pharmaceuticals for consultancy and research grants from Merck and Varian; GP has reported advisory boards/honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Janssen, Merck Sharp & Dohme, Novartis and Pfizer; BT has reported paid consultancy for Amgen, Bayer, Astellas, Ferring Pharmaceuticals, Janssen, Sanofi-Genzyme, Steba and that he is an investigator for Bayer, Astellas, Ferring Pharmaceuticals, Myovant Sciences, Janssen, Sanofi-Genzyme and Steba; SG has reported advisory role (including independent data monitoring committees) and speakers bureau for AAA International, Active Biotech AB, Amgen, Astellas Pharma, Bayer, Bristol-Myers Squibb, CellSearch, Clovis, CureVac, Dendreon, ESSA Pharma, Ferring, Innocrin Pharmaceuticals, Janssen Cilag, MaxiVAX, Millenium, Nectar, Novartis, Orion, Pfizer, ProteoMediX, Roche, Sanofi, and has reported being the co-inventor for a method for biomarker discovery (on patent application WO 2009138392 A1, granted in China, Europe, Japan and the USA).

Background: LATITUDE was the first phase 3 trial examining the survival benefit of adding abiraterone acetate (AA) + prednisone (P) to androgen-deprivation therapy (ADT) in newly diagnosed metastatic, castration-sensitive prostate cancer (mCSPC). Due to significant improvement in overall survival after the first interim analysis, patients in the placebos + ADT arm could switch to AA + P + ADT during an open-label extension. As in other studies where switching is allowed, statistical adjustments are needed to assess the real benefit of new drugs., Patients and Methods: This was a post hoc analysis to estimate the true survival benefit of AA + P + ADT in patients with newly diagnosed mCSPC by applying statistical adjustments commonly used to adjust for treatment switching., Results: Of 112 patients still receiving placebos + ADT at the first interim analysis, 72 switched to AA + P + ADT during the open-label extension. Final analysis was conducted after median follow-up of 51.8 months. Compared to the placebos + ADT arm, the risk of death in the AA + P + ADT arm was 34% lower [hazard ratio (HR) = 0.663 (95% confidence interval 0.566-0.778)] by unadjusted intent-to-treat analysis, 37% lower [HR = 0.629 (95% confidence interval 0.526-0.753)] by rank preserving structure failure time modeling, and 38% lower [HR = 0.616 (95% confidence interval 0.524-0.724)] by inverse probability of censoring weights., Conclusions: Analyses adjusting for treatment switching using two different statistical approaches confirm the improved survival benefit of adding AA + P to ADT in patients with newly diagnosed mCSPC., Trial Registration: ClinicalTrials.gov identifier NCT01715285.

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.

Background: Enzalutamide and abiraterone acetate plus prednisone, which target the androgen receptor axis, have expanded the treatment of advanced prostate cancer. Retrospective analyses suggest some cross-resistance between these two drugs when used sequentially, but robust, prospective studies have not yet been reported., Objective: To fulfil a regulatory postregistration commitment by evaluating the efficacy and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed following abiraterone acetate plus prednisone treatment., Design, Setting, and Participants: Multicentre, single-arm, open-label study, enrolled patients with progressing mCRPC after ≥24 wk of abiraterone acetate plus prednisone treatment. All patients maintained castration therapy during the trial. Prior chemotherapy was allowed but not required., Intervention: Patients received enzalutamide 160mg/d orally., Outcome Measurements and Statistical Analysis: The primary endpoint was radiographic progression-free survival. Secondary endpoints were overall survival, prostate-specific antigen (PSA) response, and time-to-PSA progression. Safety data were also assessed. Kaplan-Meier methods were used to descriptively analyse time-to-event endpoints., Results and Limitations: Overall, 214 patients received enzalutamide treatment, 145 of whom were chemotherapy-naïve. Median radiographic progression-free survival was 8.1 mo (95% confidence interval: 6.1-8.3); median overall survival had not been reached. Unconfirmed PSA response rate was 27% (48 of 181). Median time-to-PSA progression was 5.7 mo (95% confidence interval: 5.6-5.8). The most common treatment-emergent adverse events were fatigue (32%), decreased appetite (25%), asthenia (18%), back pain (17%), and arthralgia (16%). No seizures were reported., Conclusions: Enzalutamide showed antitumour activity in some patients with mCRPC who had previously progressed following ≥24 wk of abiraterone acetate plus prednisone treatment., Patient Summary: Patients with mCRPC who progressed on previous abiraterone acetate plus prednisone treatment, with or without prior chemotherapy, received enzalutamide. Although cross-resistance between the two agents was observed in a majority of patients, some still benefited from enzalutamide treatment., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Phase 3 trials have made major contributions to advances in prostate cancer (PCa). However, funding limitations and excess bureaucracy are now making it difficult to conduct trials., Objective: To describe the collaborative groups in Europe and their academic phase 3 PCa trials., Evidence Acquisition: Leaders of collaborative groups from Scandinavia, the European Organisation for Research and Treatment of Cancer (EORTC), France, Spain, the United Kingdom, Germany, Switzerland, The Netherlands, and Ireland were asked to provide information., Evidence Synthesis: Approximately 40 academic European phase 3 trials focussing on PCa have been completed, and about 10 are accruing patients. Cross-border trials have been successfully conducted led by EORTC (11), Scandinavian Prostate Cancer Group (9), European Association of Urology (1), Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficiency (STAMPEDE) (1), and the French Genito-Urinary Tumor Group (1). Among these studies were practise-changing trials showing the superiority of prostatectomy over watchful waiting in patients <65 yr of age, the benefits of combining androgen-deprivation therapy (ADT) with radiation therapy (RXT) in high-risk localised disease, the superiority of long-term versus short-term ADT, the benefit of RXT in men treated with ADT, and the role of adjuvant RXT. To bridge the numbers gap for phase 3 studies, the Prostate Cancer Consortium in Europe (PEACE) is a recently established initiative that aims to favour cross-border networks of investigators. PEACE 1 is testing the addition of abiraterone and that of RXT directed at the primary cancer in patients with de novo metastatic PCa treated with ADT. PEACE 2 is testing the addition of cabazitaxel and that of pelvic irradiation in patients with at least two criteria for high-risk localised PCa., Conclusions: European academic phase 3 trials have contributed to establishing the current standard treatment of PCa. The PEACE consortium was recently tasked with the goal of addressing unanswered questions and specific biology-related issues more efficiently., Patient Summary: The Prostate Cancer Consortium in Europe was established to conduct comparative trials aiming at assessing new treatments for prostate cancer patients., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer (PCa) after docetaxel in the randomised, phase 3, double-blind, placebo-controlled, multinational Patients with Progressive Castration-Resistant Prostate Cancer Previously Treated with Docetaxel-Based Chemotherapy (AFFIRM) trial (NCT00974311). Prostate-specific antigen (PSA) is commonly used as a marker of PCa disease burden, and the relationship of baseline PSA level to consequent treatment effect is of clinical interest., Objective: Exploratory analysis to evaluate any differences in patient characteristics and efficacy outcomes by baseline PSA level in the AFFIRM trial., Design, Setting, and Participants: Post hoc subanalysis of all randomised patients (n=1199) from the AFFIRM trial., Intervention: Participants were randomly assigned in a two-to-one ratio to receive oral enzalutamide 160 mg/d or placebo., Outcome Measurements and Statistical Analysis: The major clinical efficacy end points were overall survival (OS), radiographic progression-free survival (rPFS), and time to PSA progression (TTPP) versus placebo; baseline characteristics, treatment duration, and subsequent antineoplastic therapy were compared by baseline PSA quartile., Results and Limitations: Baseline PSA quartiles corresponded to the following PSA groups: <40 ng/ml (n=299), 40 to <111 ng/ml (n=300), 111 to <406 ng/ml (n=300), and ≥406 ng/ml (n=300). Enzalutamide consistently improved OS, rPFS, and TTPP compared with placebo across all subgroups, regardless of baseline PSA level. Hazard ratios for improvements in OS were 0.55 (95% confidence interval [CI], 0.36-0.85), 0.69 (95% CI, 0.47-1.02), 0.73 (95% CI, 0.53-1.01), and 0.53 (95% CI, 0.39-0.73) for PSA groups 1-4, respectively. The post hoc design of this analysis was not statistically powered to assess the relationship between baseline PSA and clinical efficacy outcomes., Conclusions: This post hoc analysis of the AFFIRM trial demonstrates consistent benefits in OS, rPFS, and TTPP with enzalutamide regardless of baseline disease severity, as assessed by PSA., Patient Summary: Exploratory post hoc analysis of the AFFIRM trial showed that enzalutamide improves overall survival, radiographic progression-free survival, and time to prostate-specific antigen progression compared with placebo regardless of baseline disease severity, as assessed by prostate-specific antigen., Trial Registration: ClinicalTrials.gov identifier NCT00974311., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311)., Patients and Methods: Phase III, double-blind, placebo-controlled, multinational AFFIRM trial in men with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel. Participants were randomly assigned in a 2:1 ratio to receive oral enzalutamide 160 mg/day or placebo. The primary end point was overall survival (OS) in a post hoc analysis., Results: Enzalutamide significantly improved OS compared with placebo in both EU and NA patients. The median OS in EU patients was longer than NA patients in both treatment groups. However, the relative treatment effect, expressed as hazard ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82) for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions. The tolerability profile of enzalutamide was comparable between EU and NA patients, with fatigue and nausea the most common adverse events. Four EU patients (4/461 enzalutamide-treated, 0.87%) and one NA patient (1/263 enzalutamide-treated, 0.38%) had seizures. The difference in median OS was related in part to the timing of development of mCRPC and baseline demographics on study entry., Conclusion: This post hoc exploratory analysis of the AFFIRM trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA- and EU-treated patients, although the median OS was higher in EU relative to NA patients. Efficacy benefits were consistent across end points, with a comparable safety profile in both regions., (© 2014 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Abiraterone acetate plus prednisone significantly improves radiographic progression-free survival in asymptomatic or mildly symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer compared with prednisone alone. We describe analyses of data for patient-reported pain and functional status in a preplanned interim analysis of a phase 3 trial., Methods: Between April 28, 2009, and June 23, 2010, patients with progressive, metastatic castration-resistant prostate cancer were enrolled into a multinational, double-blind, placebo-controlled trial. Patients were eligible if they were asymptomatic (score of 0 or 1 on item three of the Brief Pain Inventory Short Form [BPI-SF] questionnaire) or mildly symptomatic (score of 2 or 3) and had not previously received chemotherapy. Patients were randomly assigned (1:1) to receive oral abiraterone (1 g daily) plus prednisone (5 mg twice daily) or placebo plus prednisone in continuous 4-week cycles. Pain was assessed with the BPI-SF questionnaire, and health-related quality of life (HRQoL) with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. We analysed data with prespecified criteria for clinically meaningful pain progression and deterioration in HRQoL. All patients who underwent randomisation were included in analyses., Findings: 1088 patients underwent randomisation: 546 were assigned to abiraterone plus prednisone and 542 to placebo plus prednisone. At the time of the second prespecified interim analysis, median follow-up was 22·2 months (IQR 20·2-24·8). Median time to progression of mean pain intensity was longer in patients assigned to abiraterone plus prednisone (26·7 months [95% CI 19·3-not estimable]) than in those assigned to placebo plus prednisone (18·4 months [14·9-not estimable]; hazard ratio [HR] 0·82, 95% CI 0·67-1·00; p=0·0490), as was median time to progression of pain interference with daily activities (10·3 months [95% CI 9·3-13·0] vs 7·4 months [6·4-8·6]; HR 0·79, 95% CI 0·67-0·93; p=0·005). Median time to progression of worst pain was also longer with abiraterone plus prednisone (26·7 months [95% CI 19·4-not estimable]) than with placebo plus prednisone (19·4 months [16·6-not estimable]), but the difference was not significant (HR 0·85, 95% CI 0·69-1·04; p=0·109). Median time to HRQoL deterioration was longer in patients assigned to abiraterone plus prednisone than in those assigned to placebo plus prednisone as assessed by the FACT-P total score (12·7 months [95% CI 11·1-14·0] vs 8·3 months [7·4-10·6]; HR 0·78, 95% CI 0·66-0·92; p=0·003) and by the score on its prostate-cancer-specific subscale (11·1 months [8·6-13·8] vs 5·8 months [5·5-8·3]; HR 0·70, 95% CI 0·60-0·83; p<0·0001)., Interpretation: Abiraterone plus prednisone delays patient-reported pain progression and HRQoL deterioration in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. These results provide further support for the efficacy of abiraterone in this population., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands., Methods: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update., Results: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma., Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

Objectives: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands., Methods: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update., Results: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities., Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.

Background: The association between primary germ cell tumors of the mediastinum (the space between the lung pleura that contains the heart and other chest viscera) and hematologic malignancies has been described by retrospective analysis of patients treated at individual clinical centers. To better characterize the risk of hematologic disorders in patients with extragonadal germ cell tumors and to describe the clinical and biologic features of the disorders, we studied an unselected population in a large, international, multicenter database., Methods: Six hundred thirty-five patients treated at 11 centers in the United States and Europe from 1975 through 1996 were evaluated retrospectively., Results: A hematologic disorder was observed in 17 patients with germ cell tumors. All cases developed among the 287 patients with primary mediastinal nonseminomatous germ cell tumors, giving an incidence rate in this group of 2.0% (95% confidence interval [CI] = 1.1%-3.1%) per year over a median follow-up time of 3 years. The risk of developing hematologic disorders was statistically significantly increased in patients with primary mediastinal nonseminomatous germ cell tumors in comparison with the age-matched general population (standardized incidence ratio = 250; 95% CI = 140-405). The median time to onset of hematologic neoplasia was 6 months (range, 0-47 months), and the median survival after diagnosis of the hematologic disorder was 5 months (range, 0-16 months) (two-sided P<.0001, comparing survival from the time of diagnosis of the germ cell tumor of patients with and without hematologic disorders)., Conclusion: In our study, approximately one in 17 patients with primary mediastinal nonseminomatous germ cell tumors was affected by a hematologic disorder, whereas no cases were seen among 334 patients with other extragonadal germ cell tumors. The hematologic disorder had a statistically significant impact on prognosis, with none of the 17 reported patients surviving for more than 2 years.