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Heidenreich A.,RWTH Aachen | Bastian P.J.,Klinikum Golzheim | Bellmunt J.,University of the Sea | Bolla M.,C.H.U. Grenoble | And 6 more authors.
European Urology | Year: 2014

Context The most recent summary of the European Association of Urology (EAU) guidelines on prostate cancer (PCa) was published in 2011. Objective To present a summary of the 2013 version of the EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined PCa. Evidence acquisition A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group. The guidelines have been updated, and levels of evidence and grades of recommendation have been added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews. Evidence synthesis A full version of the guidelines is available at the EAU office or online (www.uroweb.org). Current evidence is insufficient to warrant widespread population-based screening by prostate-specific antigen (PSA) for PCa. Systematic prostate biopsies under ultrasound guidance and local anesthesia are the preferred diagnostic method. Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy. A biopsy progression indicates the need for active intervention, whereas the role of PSA doubling time is controversial. In men with locally advanced PCa for whom local therapy is not mandatory, watchful waiting (WW) is a treatment alternative to androgen-deprivation therapy (ADT), with equivalent oncologic efficacy. Active treatment is recommended mostly for patients with localized disease and a long life expectancy, with radical prostatectomy (RP) shown to be superior to WW in prospective randomized trials. Nerve-sparing RP is the approach of choice in organ-confined disease, while neoadjuvant ADT provides no improvement in outcome variables. Radiation therapy should be performed with ≥74 Gy in low-risk PCa and 78 Gy in intermediate- or high-risk PCa. For locally advanced disease, adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice. Follow-up after local therapy is largely based on PSA and a disease-specific history, with imaging indicated only when symptoms occur. Conclusions Knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice. Patient summary A summary is presented of the 2013 EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined prostate cancer (PCa). Screening continues to be done on an individual basis, in consultation with a physician. Diagnosis is by prostate biopsy. Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to androgen-deprivation therapy in locally advanced PCa not requiring immediate local treatment. Radical prostatectomy is the only surgical option. Radiation therapy can be external or delivered by way of prostate implants. Treatment follow-up is based on the PSA level. © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Mukherjee S.,University of Oxford | Hurt C.N.,University of Cardiff | Bridgewater J.,University College London | Falk S.,Bristol Haematology and Oncology Center | And 15 more authors.
The Lancet Oncology | Year: 2013

Background: In the UK, chemotherapy is the standard treatment for inoperable, locally advanced, non-metastatic pancreatic cancer. Chemoradiotherapy is also an acceptable treatment option, for which gemcitabine, fluorouracil, or capecitabine can be used as concurrent chemotherapy agents. We aimed to assess the activity, safety, and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer. Methods: In this open-label, randomised, two-arm, phase 2 trial, patients aged 18 years or older with histologically proven, locally advanced pancreatic cancer (with a tumour diameter of 7 cm or less) were recruited from 28 UK centres between Dec 24, 2009 and Oct 25, 2011. After 12 weeks of induction gemcitabine and capecitabine chemotherapy (three cycles of gemcitabine [1000 mg/m2 on days 1, 8, 15 of a 28-day cycle] and capecitabine [830 mg/m2 twice daily on days 1-21 of a 28-day cycle]), patients with stable or responding disease, tumour diameter of 6 cm or less, and WHO performance status 0-1 were randomly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine (300 mg/m2 once per week) or capecitabine (830 mg/m2 twice daily, Monday to Friday only), both in combination with radiation (50·4 Gy in 28 fractions). Randomisation (1:1) was done via a central computerised system and used stratified minimisation. The primary endpoint was 9-month progression-free survival, analysed by intention to treat including only those patients with valid CT assessments. This trial is registered with ISRCTN, number 96169987. Findings: 114 patients were registered and 74 were randomly allocated (38 to the gemcitabine group and 36 to the capecitabine group). After 9 months, 22 of 35 assessable patients (62·9%, 80% CI 50·6-73·9) in the capecitabine group and 18 of 35 assessable patients (51·4%, 39·4-63·4) in the gemcitabine group had not progressed. Median overall survival was 15·2 months (95% CI 13·9-19·2) in the capecitabine group and 13·4 months (95% CI 11·0-15·7) in the gemcitabine group (adjusted hazard ratio [HR] 0·39, 95% CI 0·18-0·81; p=0·012). 12-month overall survival was 79·2% (95% CI 61·1-89·5) in the capecitabine group and 64·2 (95% CI 46·4-77·5) in the gemcitabine group. Median progression-free survival was 12·0 months (95% CI 10·2-14·6) in the capecitabine group and 10·4 months (95% CI 8·9-12·5) in the gemcitabine group (adjusted HR 0·60, 95% CI 0·32-1·12; p=0·11). Eight patients in the capecitabine group had an objective response at 26 weeks, as did seven in the gemcitabine group. More patients in the gemcitabine group than in the capecitabine group had grade 3-4 haematological toxic effects (seven [18%] vs none, p=0·008) and non-haematological toxic effects (ten [26%] vs four [12%], p=0·12) during chemoradiation treatment; the most frequent events were leucopenia, neutropenia, and fatigue. Two patients in the capecitabine group progressed during the fourth cycle of induction chemotherapy. Of the 34 patients in the capecitabine group who received chemoradiotherapy, 25 (74%) received the full protocol dose of radiotherapy, compared with 26 (68%) of 38 patients in the gemcitabine group. Quality-of-life scores were not significantly different between the treatment groups. Interpretation: Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer. However, these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small. Funding: Cancer Research UK. © 2013 Elsevier Ltd.


Crosby T.,Velindre Hospital | Hurt C.N.,University of Cardiff | Falk S.,Bristol Haematology and Oncology Center | Gollins S.,North Wales Cancer Treatment Center | And 11 more authors.
The Lancet Oncology | Year: 2013

Background: Definitive chemoradiotherapy (CRT) is an alternative to surgery for the curative treatment of oesophageal carcinoma. The SCOPE1 trial aimed to investigate the addition of cetuximab to cisplatin and fluoropyrimidine-based definitive CRT in patients with localised oesophageal squamous-cell cancer and adenocarcinomas to assess activity, safety, and feasibility of use. Methods: In this multicentre, randomised, open-label, phase 2/3 trial, we recruited patients aged 18 years and older from UK radiotherapy centres who had non-metastatic, histologically confirmed carcinoma of the oesophagus (adenocarcinoma, squamous-cell, or undifferentiated; WHO status 0-1; stage I-III disease) and been selected to receive definitive CRT. Patients were randomly assigned (1:1) via a central computerised system using stratified minimisation (with an 80:20 random element) to receive CRT alone or CRT with cetuximab (400 mg/m2 on day 1 followed by 250 mg/m2 weekly), stratified by recruiting hospital, primary reason for not having surgery, tumour histology, and tumour stage. CRT consisted of cisplatin 60 mg/m2 (day 1) and capecitabine 625 mg/m2 twice daily (days 1-21) for four cycles; cycles three and four were given concurrently with 50 Gy in 25 fractions of radiotherapy. The primary endpoint was the proportion of patients who were treatment failure free at week 24 for the phase 2 trial and overall survival for the phase 3 trial, both measured from randomisation. We analysed data by intention to treat. This trial is an International Standard Randomised Controlled Trial, number 47718479. Findings: 258 patients (129 assigned to each treatment group) from 36 UK centres were recruited between Feb 7, 2008, and Feb 22, 2012. Recruitment was stopped without continuation to phase 3 because the trial met criteria for futility, but we continued to follow-up recruited patients until all had reached at least 24-week follow-up (median follow-up of patients who survived was 16·8 months [IQR 11·2-24·5]). Fewer patients were treatment failure free at 24 weeks in the CRT plus cetuximab group (79 of 119 patients [66·4%, 90% CI 58·6-73·6]) than in the CRT only group (93 of 121 patients [76·9%, 69·7-83·0]). The CRT plus cetuximab group also had shorter median overall survival (22·1 months [95% CI 15·1-24·5] vs 25·4 months [20·5-37·9]; adjusted HR 1·53 [95% CI 1·03-2·27]; p=0·035). Patients who received CRT plus cetuximab had more non-haematological grade 3 or 4 toxicities (102 [79%] of 129 patients vs 81 [63%] of 129 patients; p=0·004). The most common grade 3 or 4 toxicities were low white blood cell count (14 [11%] in the CRT plus cetuximab group vs 21 [16%] in the CRT only group), low absolute neutrophil count (15 [12%] vs 24 [19%]), fatigue (26 [20%] vs 25 [19%]), and dysphagia (35 [27%] vs 37 [29%]). Interpretation: The addition of cetuximab to standard chemotherapy and radiotherapy cannot be recommended for patients with oesophageal cancer suitable for definitive CRT. Funding: Cancer Research UK. © 2013 Elsevier Ltd.


Barrett-Lee P.,Velindre Hospital | Casbard A.,University of Cardiff | Abraham J.,Velindre Hospital | Hood K.,University of Cardiff | And 7 more authors.
The Lancet Oncology | Year: 2014

Background: Bisphosphonates are routinely used in the treatment of metastatic bone disease from breast cancer to reduce pain and bone destruction. Zoledronic acid given by intravenous infusion has been widely used, but places a substantial logistical burden on both patient and hospital. As a result, the use of oral ibandronic acid has increased, despite the absence of comparative data. In the ZICE trial, we compared oral ibandronic acid with intravenous zoledronic acid for the treatment of metastatic breast cancer to bone. Methods: This phase 3, open-label, parallel group active-controlled, multicentre, randomised, non-inferiority phase 3 study was done in 99 UK hospitals. Eligibility criteria included at least one radiologically confirmed bone metastasis from a histologically confirmed breast cancer. Patients with ECOG performance status 0 to 2 and clinical decision to treat with bisphosphonates within 3 months of randomisation were randomly assigned to receive 96 weeks of treatment with either intravenous zoledronic acid at 4 mg every 3-4 weeks or oral ibandronic acid 50 mg daily. Randomisation (1:1) was done via a central computerised system within stratified block sizes of four. Randomisation was stratified on whether patients had current or planned treatment with chemotherapy; current or planned treatment with hormone therapy; and whether they had a previous skeletal-related event within the last 3 months or had planned radiotherapy treatment to the bone or planned orthopaedic surgery due to bone metastases. The primary non-inferiority endpoint was the frequency and timing of skeletal-related events over 96 weeks, analysed using a per-protocol analysis. All active (non-withdrawn) patients have now reached the 96-week timepoint and the trial is now in long-term follow-up. The trial is registered with ClinicalTrials.gov, number NCT00326820. Findings: Between Jan 13, 2006, and Oct 4, 2010, 705 patients were randomly assigned to receive ibandronic acid and 699 to receive zoledronic acid; three patients withdrew immediately after randomisation. The per-protocol analysis included 654 patients in the ibandronic acid group and 672 in the zoledronic acid group. Annual rates of skeletal-related events were 0·499 (95% CI 0·454-0·549) with ibandronic acid and 0·435 (0·393-0·480) with zoledronic acid; the rate ratio for skeletal-related events was 1·148 (95% CI 0·967-1·362). The upper CI was greater than the margin of non-inferiority of 1·08; therefore, we could not reject the null hypothesis that ibandronic acid was inferior to zoledronic acid. More patients in the zoledronic acid group had renal toxic effects than in the ibandronic acid group (226 [32%] of 697 vs 172 [24%] of 704) but rates of osteonecrosis of the jaw were low in both groups (nine [1%] of 697 vs five [<1%] of 704). The most common grade 3 or 4 adverse events were fatigue (97 [14%] of 697 patients allocated zoledronic acid vs 98 [14%] of 704 allocated ibandronic acid), increased bone pain (92 [13%] vs 86 [12%]), joint pain (42 [6%] vs 38 [5%]), infection (33 [5%] vs 24 [3%]), and nausea or vomiting (38 [5%] vs 41 [6%]). Interpretation: Our results suggest that zoledronic acid is preferable to ibandronic acid in preventing skeletal-related events caused by bone metastases. However, both drugs have acceptable side-effect profiles and the oral formulation is more convenient, and could still be considered if the patient has a strong preference or if difficulties occur with intravenous infusions. Funding: Roche Products Ltd (educational grant), supported by National Institute for Health Research Cancer Network, following endorsement by Cancer Research UK (CRUKE/04/022). © 2014 Elsevier Ltd.


Hoskin P.J.,Mount Vernon Cancer Center | Kirkwood A.A.,University College London | Popova B.,University College London | Smith P.,University College London | And 9 more authors.
The Lancet Oncology | Year: 2014

Background: Follicular lymphoma has been shown to be highly radiosensitive with responses to doses as low as 4 Gy in two fractions. This trial was designed to explore the dose response for follicular lymphoma comparing 4 Gy in two fractions with 24 Gy in 12 fractions. Methods: FORT is a prospective randomised, unblinded, phase 3 non-inferiority study comparing radiotherapy given as 4 Gy in two fractions with a standard dose of 24 Gy in 12 fractions. Entry criteria included all patients aged over 18 years, having local radiotherapy for radical or palliative local control, with follicular lymphoma or marginal zone lymphoma, who had received no previous treatment for at least 1 month before. The primary outcome was time to local progression analysed on an intention-to-treat basis. Randomisation was centralised through the Cancer Research UK and University College London Cancer Trials Centre. Radiotherapy target sites were randomised (1:1) with minimisation stratified by histology (follicular lymphoma vs marginal zone lymphoma), treatment intent (palliative or curative) and centre. This trial is registered with ClinicalTrials.gov number, NCT00310167. Findings: 299 sites were randomly assigned to 24 Gy and 315 sites to 4 Gy between April 7, 2006, and June 8, 2011, at 43 centres in the UK. After a median follow-up of 26 months (range 0·39-75·4), 91 local progressions had been recorded (21 in the 24 Gy group and 70 in the 4 Gy group). Time to local progression with 4 Gy was not non-inferior to 24 Gy (hazard ratio 3·42, 95% CI 2·09-5·55, p<0·0001). Eight (3%) of 282 patients in the 24 Gy group and four (1%) of 300 in the 4 Gy group had acute grade 3-4 toxic effects. Four (1%) patients in the 24 Gy group and four (1%) patients in the 4 Gy group had late toxic effects. Mucositis was the most common event in the 24 Gy group (two patients with acute mucositis and two with late mucositis; all grade 3) and was not reported in the 4 Gy group. The most common acute effect was pain at the site of irradiation (two patients in the 4 Gy group, one patient in the 24 Gy group; all grade 3), and the most common late effect was fatigue (two patients in the 4 Gy group, one patient in the 24 Gy group; all grade 3). Interpretation: 24 Gy in 12 fractions is the more effective radiation schedule for indolent lymphoma and should be regarded as the standard of care. However, 4 Gy remains a useful alternative for palliative treatment. Funding: Cancer Research UK. © 2014 Elsevier Ltd.


Heidenreich A.,RWTH Aachen | Bellmunt J.,University of the Sea | Bolla M.,C.H.U. Grenoble | Joniau S.,University Hospital Gasthuisberg | And 5 more authors.
European Urology | Year: 2011

Objective: Our aim was to present a summary of the 2010 version of the European Association of Urology (EAU) guidelines on the screening, diagnosis, and treatment of clinically localised cancer of the prostate (PCa). Methods: The working panel performed a literature review of the new data emerging from 2007 to 2010. The guidelines were updated, and level of evidence and grade of recommendation were added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews. Results: A full version is available at the EAU office or Web site (www.uroweb.org). Current evidence is insufficient to warrant widespread population-based screening by prostate-specific antigen (PSA) for PCa. A systematic prostate biopsy under ultrasound guidance and local anaesthesia is the preferred diagnostic method. Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy. PSA doubling time in <3 yr or a biopsy progression indicates the need for active intervention. In men with locally advanced PCa in whom local therapy is not mandatory, watchful waiting (WW) is a treatment alternative to androgen-deprivation therapy (ADT) with equivalent oncologic efficacy. Active treatment is mostly recommended for patients with localised disease and a long life expectancy with radical prostatectomy (RP) shown to be superior to WW in a prospective randomised trial. Nerve-sparing RP represents the approach of choice in organ-confined disease; neoadjuvant androgen deprivation demonstrates no improvement of outcome variables. Radiation therapy should be performed with at least 74 Gy and 78 Gy in low-risk and intermediate/high-risk PCa, respectively. For locally advanced disease, adjuvant ADT for 3 yr results in superior disease-specific and overall survival rates and represents the treatment of choice. Follow-up after local therapy is largely based on PSA, and a disease-specific history with imaging is indicated only when symptoms occur. Conclusions: The knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. © 2010 European Association of Urology.


Bellmunt J.,University of the Sea | Bolla M.,C.H.U. Grenoble | Joniau S.,University Hospital | Mason M.,Velindre Hospital | And 5 more authors.
European Urology | Year: 2011

Objectives: Our aim is to present a summary of the 2010 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC). Methods: The working panel performed a literature review of the new data emerging from 2007 to 2010. The guidelines were updated, and the levels of evidence (LEs) and/or grades of recommendation (GR) were added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews. Results: Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). Although LHRH antagonists decrease testosterone without any testosterone surge, their clinical benefit remains to be determined. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation (IAD) results in equivalent oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (CT) are of limited importance if the PSA is <2.5 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include screening for the metabolic syndrome and an analysis of PSA and testosterone levels. Treatment of castration-resistant prostate cancer (CRPC) includes second-line hormonal therapy, novel agents, and chemotherapy with docetaxel at 75 mg/m2 every 3 wk. Cabazitaxel as a second-line therapy for relapse after docetaxel might become a future option. Zoledronic acid and denusomab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications. Conclusion: The knowledge in the field of advanced, metastatic, and CRPC is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. A full version is available at the EAU office or online at www.uroweb.org. © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.


James R.D.,Kent Cancer Center | Glynne-Jones R.,Mount Vernon Hospital | Meadows H.M.,University College London | Cunningham D.,Royal Marsden Hospital | And 13 more authors.
The Lancet Oncology | Year: 2013

Background: Chemoradiation became the standard of care for anal cancer after the ACT I trial. However, only two-thirds of patients achieved local control, with 5-year survival of 50%; therefore, better treatments are needed. We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response, and whether maintenance chemotherapy after chemoradiation improves survival. Methods: In this 2×2 factorial trial, we enrolled patients with histologically confirmed squamous-cell carcinoma of the anus without metastatic disease from 59 centres in the UK. Patients were randomly assigned to one of four groups, to receive either mitomycin (12 mg/m2 on day 1) or cisplatin (60 mg/m2 on days 1 and 29), with fluorouracil (1000 mg/m2 per day on days 1-4 and 29-32) and radiotherapy (50·4 Gy in 28 daily fractions); with or without two courses of maintenance chemotherapy (fluorouracil and cisplatin at weeks 11 and 14). The random allocation was generated by computer and patients assigned by telephone. Randomisation was done by minimisation and stratified by tumour site, T and N stage, sex, age, and renal function. Neither patients nor investigators were masked to assignment. Primary endpoints were complete response at 26 weeks and acute toxic effects (for chemoradiation), and progression-free survival (for maintenance). The primary analyses were done by intention to treat. This study is registered at controlled-trials.com, number 26715889. Findings: We enrolled 940 patients: 472 were assigned to mitomycin, of whom 246 were assigned to no maintenance, 226 to maintenance; 468 were assigned to cisplatin, of whom 246 were assigned to no maintenance, 222 to maintenance. Median follow-up was 5·1 years (IQR 3·9-6·9). 391 of 432 (90·5%) patients in the mitomycin group versus 386 of 431 (89·6%) in the cisplatin group had a complete response at 26 weeks (difference -0·9%, 95% CI -4·9 to 3·1; p=0·64). Overall, toxic effects were similar in each group (334/472 [71%] for mitomycin vs 337/468 [72%] for cisplatin). The most common grade 3-4 toxic effects were skin (228/472 [48%] vs 222/468 [47%]), pain (122/472 [26%] vs 135/468 [29%]), haematological (124/472 [26%] vs 73/468 [16%]), and gastrointestinal (75/472 [16%] vs 85/468 [18%]). 3-year progression-free survival was 74% (95% CI 69-77; maintenance) versus 73% (95% CI 68-77; no maintenance; hazard ratio 0·95, 95% CI 0·75-1·21; p=0·70). Interpretation: The results of our trial-the largest in anal cancer to date-show that fluorouracil and mitomycin with 50·4 Gy radiotherapy in 28 daily fractions should remain standard practice in the UK. Funding: Cancer Research UK. © 2013 Elsevier Ltd.


Heidenreich A.,RWTH Aachen | Bastian P.J.,Klinikum Golzheim | Bellmunt J.,University of the Sea | Bolla M.,Grenoble University Hospital Center | And 7 more authors.
European Urology | Year: 2014

Objective To present a summary of the 2013 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC). Evidence acquisition The working panel performed a literature review of the new data (2011-2013). The guidelines were updated, and levels of evidence and/or grades of recommendation were added to the text based on a systematic review of the literature that included a search of online databases and bibliographic reviews. Evidence synthesis Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they may be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT (SRT) at PSA levels <0.5 ng/ml and SRP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel at 75 mg/m2 every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications. Conclusions The knowledge in the field of advanced, metastatic, and castration-resistant PCa is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. A full version is available at the EAU office or at www.uroweb.org. Patient summary We present a summary of the 2013 version of the European Association of Urology guidelines on treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC). Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they might be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy. Therapy for PSA relapse after RP includes salvage radiation therapy at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Multiparametric magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans, and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of castration-resistant CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel 75 mg/m2 every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications. The guidelines reported should be adhered to in daily routine to improve the quality of care in PCa patients. As we have shown recently, guideline compliance is only in the area of 30-40%. © 2013 European Association of Urology.


Hudson E.,Velindre Hospital | Lester J.F.,Velindre Hospital
European Journal of Cancer Care | Year: 2010

The objectives of this study are to evaluate patient outcomes in clinical practice using gemcitabine and carboplatin (GCarbo) as first-line treatment in metastatic transitional cell carcinoma (TCC) of the urothelium, and to review the published evidence on the use of GCarbo in this setting. From July 2003, all cases of metastatic TCC of the urothelium referred to a single consultant were treated using 3-weekly gemcitabine 1200 mg/m2 i.v. days 1 and 8 plus carboplatin AUC 5-6 i.v. day 1 to a maximum of six cycles. Fifteen patients (median age 67 years) were treated. Grade 3 or 4 toxicity included neutropenia (47%), anaemia (27%) and thrombocytopenia (20%). No patients required admission for neutropenic pyrexia/sepsis, and there were no treatment-related deaths. The overall response rate was 67%. The median survival was 9 months (95% CI 7.4-10.6), and 1-year survival 42%. Gemcitabine and carboplatin is well tolerated, and has activity as first-line treatment in metastatic TCC of the urothelium. However, there is now evidence suggesting that gemcitabine and cisplatin may be more efficacious, and until the appropriate randomized phase 3 trials have been carried out, gemcitabine and cisplatin should probably remain the preferred first-line therapy. Gemcitabine and carboplatin is an effective alternative in those patients not deemed fit enough for cisplatin. © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.

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