Prostatic Neoplasms: Bolla M

Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP, Zattoni F, Anonymous00089. · Servicio de Urología, Hospital Universitario de Colonia, Colonia, Alemania. · Actas Urol Esp. · Pubmed #19418833 links to  free full text

Abstract: OBJECTIVES: To present a summary of the 2007 version of the European Association of Urology (EAU) guidelines on prostate cancer (PCa). METHODS: A literature review of the new data emerging from 2004 to 2007 was performed by the working panel. The guidelines have been updated, and the level of evidence/grade of recommendation was 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 at www.uroweb.org. Systemic prostate biopsy under ultrasound guidance is the preferred diagnostic method. Active treatment is mostly recommended for patients with localized disease and a long life expectancy, with radical prostatectomy being shown to be superior to watchful waiting in a prospective randomized trial. Nerve-sparing radical prostatectomy 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 72 and 78 Gy in low-risk and intermediate- to high-risk PCa, respectively. Monotherapeutic androgen deprivation is the standard of care in metastatic PCa; intermittent androgen deprivation might be an alternative treatment option for selected patients. Follow-up is largely based on prostate-specific antigen and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy with docetaxel has emerged as the reference treatment for metastatic hormone-refractory PCa. CONCLUSIONS: The 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.

Boehmer D, Maingon P, Poortmans P, Baron MH, Miralbell R, Remouchamps V, Scrase C, Bossi A, Bolla M, Anonymous00259. · Klinik f. Strahlentherapie, Universitätsmedizin Berlin, Charité Campus Mitte, Germany. · Radiother Oncol. · Pubmed #16797094 No free full text.

Abstract: BACKGROUND AND PURPOSES: The appropriate application of 3-D conformal radiotherapy, intensity modulated radiotherapy or image guided radiotherapy for patients undergoing radiotherapy for prostate cancer requires a standardisation of target delineation as well as clinical quality assurance procedures. PATIENTS AND METHODS: Pathological and imaging studies provide valuable information on tumour extension. In addition, clinical investigations on patient positioning and immobilisation as well as treatment verification data offer an abundance of information. RESULTS: Target volume definitions for different risk groups of prostate cancer patients based on pathological and imaging studies are provided. Available imaging modalities, patient positioning and treatment preparation studies as well as verification procedures are collected from literature studies. These studies are summarised and recommendations are given where appropriate. CONCLUSIONS: On behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group this article presents a common set of recommendations for external beam radiotherapy of patients with prostate cancer.

Aus G, Abbou CC, Bolla M, Heidenreich A, Schmid HP, van Poppel H, Wolff J, Zattoni F, Anonymous00098. · No affiliation provided · Eur Urol. · Pubmed #16046052 No free full text.

Abstract: OBJECTIVES: The first summary of the European Association of Urology (EAU) guidelines on prostate cancer was published in 2001. These guidelines have been continuously updated since many important changes affecting the clinical management of patients with prostate cancer have occurred over the past years. The aim of this paper is to present a summary of the 2005 update of the EAU guidelines on prostate cancer. METHODS: A literature review of the new data has been performed by the working panel. The guidelines have been updated and level of evidence/grade of recommendation added to the text. This enables readers to better understand the quality of the data forming the basis of the recommendations. RESULTS: A full version is available at the EAU Office or at . Systemic prostate biopsies under ultrasound guidance is the preferred diagnostic method and the use of periprostatic injection of a local anaesthetic can significantly reduce pain/discomfort associated with the procedure. Active treatment (surgery or radiation) is mostly recommended for patients with localized disease and a long life expectancy with radical prostatectomy being the only treatment evaluated in a randomized controlled trial. Follow-up is at large based on prostate specific antigen (PSA) and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy has become an option for selected patients with hormone refractory prostate cancer. CONCLUSION: The knowledge in the field of prostate cancer is rapidly changing. These EAU guidelines on prostate cancer summarize the most recent findings and put them into clinical practice.

Bolla M. · No affiliation provided · Eur Urol. · Pubmed #18295394 No free full text.

This publication has no abstract.

Bolla M, Fourneret P, Descotes JL. · Clinique universitaire de cancérologie-radiothérapie, centre hospitalier universitaire, Grenoble, France. · Bull Cancer. · Pubmed #19091656 No free full text.

Abstract: Treatment of high-risk prostate cancer - localized or locally advanced - is based on the combination of external irradiation and hormonal treatment by LHRH analogue (aLHRH) according to the results of phases III randomized trials RTOG and/or EORTC trials. These trials show a significant improvement of overall or specific survival. Localized prostate cancer require 6-month complete androgen blockade, while locally advanced prostate cancer need a long-term hormonal treatment for a duration ranging from 2,5 to 3 years. Some trials, which have a long follow-up show that the risk of cardiovascular death is not significantly increased by hormonal treatment.

Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP, Zattoni F, Anonymous00006. · Department of Urology, University Hospital Cologne, Cologne, Germany. · Eur Urol. · Pubmed #17920184 No free full text.

Abstract: OBJECTIVES: To present a summary of the 2007 version of the European Association of Urology (EAU) guidelines on prostate cancer (PCa). METHODS: A literature review of the new data emerging from 2004 to 2007 was performed by the working panel. The guidelines have been updated, and the level of evidence/grade of recommendation was 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 at www.uroweb.org. Systemic prostate biopsy under ultrasound guidance is the preferred diagnostic method. Active treatment is mostly recommended for patients with localized disease and a long life expectancy, with radical prostatectomy being shown to be superior to watchful waiting in a prospective randomized trial. Nerve-sparing radical prostatectomy 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 72 and 78 Gy in low-risk and intermediate- to high-risk PCa, respectively. Monotherapeutic androgen deprivation is the standard of care in metastatic PCa; intermittent androgen deprivation might be an alternative treatment option for selected patients. Follow-up is largely based on prostate-specific antigen and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy with docetaxel has emerged as the reference treatment for metastatic hormone-refractory PCa. CONCLUSIONS: The 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.

Bolla M, Descotes JL, Artignan X, Fourneret P. · Department of Radiation Oncology, Albert Michallon University Hospital, Grenoble, France. · BJU Int. · Pubmed #17594359 No free full text.

This publication has no abstract.

Bolla M, Artignan X, Fourneret P, Brochon D, Ringeisen F, Descotes JL. · Département de cancérologie-hématologie, Service d'urologie, Centre hospitalier universitaire, BP 392, 63011 Grenoble. · Bull Cancer. · Pubmed #17145579 links to  free full text

Abstract: RTOG and EORTC trials have paved the way of the combination of radiation therapy and androgen suppression. Localized carcinoma with intermediate prognostic factors (cT2b, Gleason 7, or baseline PSA ranging between 10 and 20 ng/mL) may be submitted to a 4-month complete androgene blockade with 2 months before irradiation, unless to include patients in ongoing randomized trials. High risk cancers (cT2c, or Gleason > 7, or PSA > 20 ng/ml) should receive a 4-month or 6-month complete androgen blockade (RTOG trial 86-10), knowing that the results of EORTC trial 22961 are eagerly expected to tell us whether a 3- year androgen suppression is preferable. Very high risk prostate cancers, T3-4 N0 M0 or pelvic lymph node involvement (c or pN1) whatever the UICC T stage, need a long term androgen suppression of 3 years or more.

Artignan X, Rastkhah M, Balosso J, Fourneret P, Gilliot O, Bolla M. · Service de Radiothérapie, CHU de Grenoble, Boulevard de la Chantourne, 38700 La Tronche, France. · Cancer Radiother. · Pubmed #17049293 No free full text.

Abstract: Decrease treatment uncertainties is one of the most important challenge in radiation oncology. Numerous techniques are available to quantify prostate motion and visualise prostate location day after day before each irradiation: CT-scan, cone-beam-CT-Scan, ultrason, prostatic markers... The knowledge of prostate motion is necessary to define the minimal margin around the target volume needed to avoid mispositioning during treatment session. Different kind of prostate movement have been studied and are reported in the present work: namely, those having a large amplitude extending through out the whole treatment period on one hand; and those with a shorter amplitude happening during treatment session one the other hand. The long lasting movement are mostly anterior-posterior (3 mm standard deviation), secondary in cranial-caudal (1-2 mm standard deviation) and lateral directions (0.5-1 mm standard deviation). They are mostly due to the rectal state of filling and mildly due to bladder filling or inferior limbs position. On the other hand, the shorter movement that occurs during the treatment session is mostly variation of position around a steady point represented by the apex. Ones again, the rectal filling state is the principle cause. This way, during the 20 minutes of a treatment session, including the positioning of the patient, a movement of less than 3 mm could be expected when the rectum is empty. Ideally, real time imaging tools should allow an accurate localisation of the prostate and the adaptation of the dosimetry before each treatment session in a time envelope not exceeding 20 minutes.

Maingon P, Bolla M, Truc G, Bosset M, Peignaux K, Ammor A. · Département de radiothérapie, centre Georges-François-Leclerc, 1, rue du Professeur-Marion, 21079 Dijon cedex, France. · Cancer Radiother. · Pubmed #16095944 No free full text.

Abstract: Conformal radiation therapy has now to be considered as a standard treatment of localized prostatic adenocarcinomas. Using conformational methods and intensity modulated radiation therapy requires a rigorous approach for their implementation in routine, focused on the reproducibility of the treatment, target volume definitions, dosimetry, quality control, setup positioning. In order to offer to the largest number of patients high-dose treatment, the clinicians must integrate as prognostic factors accurate definition of microscopic extension as well as the tolerance threshold of critical organs. High-dose delivery is expected to be most efficient in intermediary risks and locally advanced diseases. Intensity modulated radiation therapy is specifically dedicated to dose escalation. Perfect knowledge of classical constraints of conformal radiation therapy is required. Using such an approach in routine needs a learning curve including the physicists and a specific quality assurance program.

Bolla M. · Service de cancérologie, radiothérapie, centre hospitalier universitaire Albert-Michallon, BP 217, Grenoble, France. · Cancer Radiother. · Pubmed #11194946 No free full text.

Abstract: Localized prostate cancer can be treated by surgery, 3D conformal radiotherapy, brachytherapy: age, clinical stage, Gleason grade, baseline PSA, multidisciplinary approach enable physicians to tailor the therapeutic strategy. Patients are more informed of therapeutic morbidity and health related quality of life and want to give their feeling. Clinical research remains mandatory to set up the treatment policy with more objectivity.

Van Poppel H, Vanuytsel L, Petrovich Z, Baert L, Boccon-Gibod L, Bolla M, Artignan X, Balosso J, Chirpaz E. · Department of Urology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium. · Eur J Cancer. · Pubmed #10673989 No free full text.

This publication has no abstract.

Chauvet B, Oozeer R, Bey P, Pontvert D, Bolla M. · Institut Sainte-Catherine, Avignon, France. · Cancer Radiother. · Pubmed #10572509 No free full text.

Abstract: Recent progress in radiotherapeutic management of localized prostate cancer is reviewed. Clinical aspects--including dose-effect beyond 70 Gy, relative role of conformal radiation therapy techniques and of early hormonal treatment--are discussed as well as technical components--including patient immobilization, organ motion, prostate contouring, beam arrangement, 3-D treatment planning and portal imaging. The local control and biological relapse-free survival rates appear to be improved by high dose conformal radiotherapy from 20 to 30% for patients with intermediate and high risk of relapse. A benefit of overall survival is expected but not yet demonstrated. Late reactions, especially the rectal toxicity, remain moderate despite the dose escalation. However, conformal radiotherapy demands a high precision at all steps of the procedure.

Matzinger O, Poortmans P, Giraud JY, Maingon P, Budiharto T, van den Bergh AC, Davis JB, Musat E, Ataman F, Huyskens DP, Gulyban A, Bolla M, Anonymous00028. · EORTC Headquarters, Belgium. · Radiother Oncol. · Pubmed #19038468 No free full text.

Abstract: INTRODUCTION: EORTC trial 22991 was designed to evaluate the addition of concomitant and adjuvant short-term hormonal treatments to curative radiotherapy in terms of disease-free survival for patients with intermediate risk localized prostate cancer. In order to assess the compliance to the 3D conformal radiotherapy protocol guidelines, all participating centres were requested to participate in a dummy run procedure. An individual case review was performed for the largest recruiting centres as well. MATERIALS AND METHODS: CT-data of an eligible prostate cancer patient were sent to 30 centres including a description of the clinical case. The investigator was requested to delineate the volumes of interest and to perform treatment planning according to the protocol. Thereafter, the investigators of the 12 most actively recruiting centres were requested to provide data on five randomly selected patients for an individual case review. RESULTS: Volume delineation varied significantly between investigators. Dose constraints for organs at risk (rectum, bladder, hips) were difficult to meet. In the individual case review, no major protocol deviations were observed, but a number of dose reporting problems were documented for centres using IMRT. CONCLUSIONS: Overall, results of this quality assurance program were satisfactory. The efficacy of the combination of a dummy run procedure with an individual case review is confirmed in this study, as none of the evaluated patient files harboured a major protocol deviation. Quality assurance remains a very important tool in radiotherapy to increase the reliability of the trial results. Special attention should be given when designing quality assurance programs for more complex irradiation techniques.

van der Kwast TH, Collette L, Van Poppel H, Van Cangh P, Vekemans K, DaPozzo L, Bosset JF, Kurth KH, Schröder FH, Bolla M, Anonymous00359. · Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada, and Department of Urology, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium. · Virchows Arch. · Pubmed #16941153 No free full text.

Abstract: Pathological staging and surgical margin status of radical prostatectomy specimens are next to grading the most important prognosticators for recurrence. A central review of pathological stage and surgical margin status was performed on a series of 552 radical prostatectomy specimens of patients, participating in the European Organisation for Research and Treatment of Cancer trial 22911. Inclusion criteria of the trial were pathological stage pT3 and/or positive surgical margin at local pathology. All specimens were totally embedded. Data of the central review were compared with those of local pathologists and related to clinical follow-up. Although a high concordance between review pathology and local pathologists existed for seminal vesicle invasion (94%, kappa=0.83), agreement was much less for extraprostatic extension (57.5%, kappa=0.33) and for surgical margin status (69.4%, kappa=0.45). Review pathology of surgical margin status was a stronger predictor of biochemical progression-free survival in univariate analysis [hazard ratio (HR)=2.16 and p=0.0002] than local pathology (HR=1.08 and p>0.1). The review pathology demonstrated a significant difference between those with and without extraprostatic extension (HR=1.83 and p=0.0017), while local pathology failed to do so (HR=1.05 and p>0.8). The observations suggest that review of pathological stage and surgical margin of radical prostatectomy strongly improves their prognostic impact in multi-institutional studies or trials.

Bolla M, Maingon P, Fourneret P, Artignan X, Descotes JL. · Département de cancérologie-hématologie, CHU de Grenoble, France. · Cancer Radiother. · Pubmed #16226044 No free full text.

Abstract: RTOG and EORTC randomised phase III trials investigated combination of radiation therapy and hormonal treatment in locally advanced prostate cancer T2c-T4 N0-1 M0 (UICC 2002). Complete androgen blockade initiated 2 months prior to starting radiotherapy and stopped at the completion of radiotherapy vs radiation therapy alone, increased overall survival in patients with Gleason score 2-6. Adjuvant androgen suppression started at the end of the radiotherapy and continued indefinitely improved significantly overall survival of patients Gleason score 8 to 10. Complete androgen blockade in two months before and two months during radiation followed by 24 additional months of LHRH analogue alone improved overall survival of patients Gleason score 8-10 with respect to CAB alone. EORTC trial 22861 has shown that androgen suppression with LHRH analogue given during and for 3 years after external irradiation improved overall survival whatever the Gleason score. The role of hormonal treatment is currently assessed in localized prostate cancer (T1-2 N0) with poor prognostic factors: Gleason score 8-10, PSA>20 ng/ml.

Collette L, van Poppel H, Bolla M, van Cangh P, Vekemans K, Da Pozzo L, de Reijke TM, Verbaeys A, Bosset JF, Piérart M, Anonymous00389. · European Organisation for Research and Treatment of Cancer (EORTC) Data Center--Biostatistics, Avenue E. Mounier 83/11, B-1200, Brussels, Belgium. · Eur J Cancer. · Pubmed #16223581 No free full text.

Abstract: EORTC trial 22911 demonstrated that immediate postoperative irradiation significantly improved biochemical failure free survival (BPFS) compared to wait-and-see (W and S) until relapse in patients with pT2-3 tumours and pathological risk factors after radical prostatectomy. In this study, we have investigated the heterogeneity of the treatment benefit across defined subgroups of patients. Data from 972 patients were used. A risk model was developed in the W and S group and the Log-rank test for heterogeneity was applied (alpha=0.05). Positive surgical margin (SM+), seminal vesicle invasion (SV+), WHO differentiation grade, pre- and post-operative PSA were independent predictors for BPFS in the W and S group. Men with SV+ were at higher risk of relapse whereas those with SM+ but no capsule infiltration (ECE-) did not seem to differ from those with SM-ECE+ or with SM+ECE+. Postoperative irradiation improved biochemical progression-free survival in all patient groups. Longer follow-up is needed to assess the endpoint of clinical progression-free survival.

Bolla M, van Poppel H, Collette L, van Cangh P, Vekemans K, Da Pozzo L, de Reijke TM, Verbaeys A, Bosset JF, van Velthoven R, Maréchal JM, Scalliet P, Haustermans K, Piérart M, Anonymous00253. · Department of Radiation Oncology, Centre Hospitalier Universitaire A Michallon, Grenoble, France. · Lancet. · Pubmed #16099293 No free full text.

Abstract: BACKGROUND: Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer. METHODS: After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat. FINDINGS: The median age was 65 years (IQR 61-69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74.0%, 98% CI 68.7-79.3 vs 52.6%, 46.6-58.5; p<0.0001). Clinical progression-free survival was also significantly improved (p=0.0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (p=0.0726). INTERPRETATION: Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival.

Kouloulias VE, Giraud JY, Davis BJ, Dusserre A, Zurlo A, Bolla M. · EORTC, DATA CENTER, Av. Mounier 83, B-1200, Brussels, Belgium. · Radiother Oncol. · Pubmed #15465141 No free full text.

Abstract: PURPOSE: The EORTC trial 22961, opened in 1997, was designed to investigate the optimal combination of hormonal adjuvant treatment by LHRH analogue and radiation therapy for the management of locally advanced prostate cancer. A dummy run was established to assess centre compliance to the radiotherapy protocol. MATERIALS AND METHODS: Medical and anatomical data obtained from 37 CT slices (5mm thickness) of an eligible patient were sent to 19 participating centres, which were asked to complete a questionnaire according to their practice and plan a theoretical radiotherapy treatment. The Planning Target Volume 1 (PTV1) should include prostate, seminal vesicles, internal iliac lymph nodes and inferior part of common iliac lymph nodes (extended pelvic fields). Centres which usually irradiate with small pelvic fields (N0 patients), were allowed to include the prostate, seminal vesicles and internal iliac lymph nodes plus a safety margin of 2 cm. For the Planning Target Volume 2 (PTV2), a safety margin of 1.5 to 2 cm should be around the prostate and seminal vesicles. Checks included patient positioning, treatment simulation, target volume definition, treatment set-up and clinical controls during treatment. RESULTS: Eleven institutions with actual 81% of patients' accrual in the protocol have responded. All centres used a supine treatment position and positioning lasers for the set-up, while 73 and 45% of the centres performed cystograms and used rectal contrast, respectively. Among the participating centres, 45% and 55% used blocks and MLC, respectively, to treat patients. Extended pelvic fields in terms of PTV1 were used by 63% of the centres. The remaining centres treated a small PTV1 with a 10-20 mm margin around to CTV1. All centres defined PTV2 according to protocol guidelines. Doses to PTV1 and PTV2 were correctly prescribed. It was difficult to assess the treated volumes due to a lack of standardisation in DVH calculations. CONCLUSION: In general, centres participating in the dummy run adhered to the guidelines. The dummy run enhances the reliability of the conclusions of the trial.

Ataman F, Zurlo A, Artignan X, van Tienhoven G, Blank LE, Warde P, Dubois JB, Jeanneret W, Keuppens F, Bernier J, Kuten A, Collette L, Pierart M, Bolla M. · EORTC Data Center, Radiotherapy Group, Avenue E. Mounier 83, bte 11, B-1200 Brussels, Belgium. · Eur J Cancer. · Pubmed #15251156 No free full text.

Abstract: Late toxicity and other serious adverse events (SAE) were analysed in the European Organisation for Research and Treatment of Cancer (EORTC) trial 22863. The study evaluated the value of adjuvant endocrine treatment for locally advanced prostate cancer treated with radiotherapy. From 1987 to 1995, 415 patients were randomised. There was long-term toxicity information for 377 patients (91%). Median age was 70 years (range 50-80 years). Median follow-up for late toxicity was 42 months (range 3-136 months). Toxicity was graded according to a modified Radiotherapy and Oncology Group (RTOG) scale. Other late SAE, that was not classified as severe treatment toxicity, but were still life-threatening, were also assessed. There were 72 patients with grade 2, 10 patients with grade 3 and 4 patients with grade 4 toxicity. There were 20 patients with other late SAE, who were grouped according to their relationship to treatment; likely related (n = 1), unrelated (n = 7) and not assessable (n = 12). Although four treatment-related deaths (1%) occurred, grade 3 or 4 late complications were less than 5%.

Davis JB, Reiner B, Dusserre A, Giraud JY, Bolla M, Anonymous00346. · Radiation Oncology, University Hospital Zurich, Ramistrasse 100, 8091, Zurich, Switzerland. · Radiother Oncol. · Pubmed #12208577 No free full text.

Abstract: INTRODUCTION: A dry run of a clinical trial (EORTC 22911) is presented in which 12 centres have participated. These are the centres which have contributed the largest number of patients to the trial. MATERIAL AND METHODS: Each participating centre received data from a suitable patient. Investigators were asked to plan and 'treat' the patient according to the protocol guidelines and return the data for evaluation of compliance. RESULTS: The results show that compliance to the protocol guidelines was generally good. There were a few minor deviations in the dose and fractionation schedule, in the volume reduction for the booster dose and in the dose prescription point. None of these deviations will affect the outcome of the study. The most important observation is the large inter-centre variation in target volumes. CONCLUSIONS: The results of this study underlines the need for a strict definition of the target volume and the adoption of the ICRU 50 recommendations in future protocols.

Zurlo A, Collette L, van Tienhoven G, Blank L, Warde P, Dubois J, Jeanneret W, Storme G, Bernier J, Kuten A, Pierart M, Bolla M, Anonymous00142. · EORTC Data Center, Avenue E. Mounier 83, 1200, Brussels, Belgium. · Eur Urol. · Pubmed #12160582 No free full text.

Abstract: OBJECTIVES: We analysed the acute toxicity observed in the European Organisation for Research and Treatment of Cancer (EORTC) randomised trial 22863 comparing conventional external irradiation with or without an agonist analogue of gonadotropin-releasing hormone in high-risk prostate cancer patients.METHODS: Four hundred five patients that received a dose of at least 30 Gy were considered evaluable for acute toxicity assessment. Toxicity was grouped in a few categories: general, genito-urinary, and lower gastro-intestinal. Univariate and multivariate analyses were performed using the World Health Organisation (WHO) toxicity score and grouping together toxicity scores in different bimodal and trimodal groups.RESULTS: Overall, our data show that age, previous surgery and irradiation dose are important predictive factors for acute toxicity, but not the use of combined hormone therapy. Fifteen percent of patients suffered of moderate to severe acute toxicity (WHO G3-G4). Life threatening toxicity was observed in six cases (1.5%).CONCLUSIONS: The assessment of toxicity combining in different groups the original five scores scale produced conflicting results similar to those commonly reported in literature. Interpretation of the role of pre-treatment factors with uneven distribution in the study requires careful evaluation. These data obtained with conventional curative irradiation of high-risk prostate cancer patients are proposed for comparison with results achieved using modern state-of-the-art irradiation techniques.

Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Pierart M. · University Hospital, Grenoble, France · Lancet. · Pubmed #12126818 No free full text.

Abstract: BACKGROUND: We did a randomised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone (LHRH) to investigate the added value of long-term androgen suppression in locally advanced prostate cancer. METHODS: Between 1987 and 1995, 415 patients were randomly assigned radiotherapy alone or radiotherapy plus immediate androgen suppression. Eligible patients had T1-2 tumours of WHO grade 3 or T3-4 N0-1 M0 tumours; the median age of participants was 71 years (range 51-80). In both treatment groups, 50 Gy radiation was delivered to the pelvis over 5 weeks, and 20 Gy over 2 weeks as a prostatic boost. Goserelin (3.6 mg subcutaneously every 4 weeks) was started on the first day of irradiation and continued for 3 years; cyproterone acetate (150 mg orally) was given for 1 month starting 1 week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analyses were by intention to treat. FINDINGS: 412 patients had evaluable data, with median follow-up of 66 months (range 1-126). 5-year clinical disease-free survival was 40% (95% CI 32-48) in the radiotherapy-alone group and 74% (67-81) in the combined-treatment group (p=0.0001). 5-year overall survival was 62% (52-72) and 78% (72-84), respectively (p=0.0002) and 5-year specific survival 79% (72-86) and 94% (90-98). INTERPRETATION: Immediate androgen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer.

Neymark N, Adriaenssen I, Gorlia T, Caleo S, Bolla M. · EORTC Health Economics Unit, Brussels, Belgium. · Health Econ. · Pubmed #11921320 No free full text.

Abstract: The problem of estimating expected outcomes for the economic evaluation of treatments for which the outcome of principal interest is (quality adjusted) survival time has so far not received sufficient attention in the literature. The best estimate of expected survival is mean survival time, but with censored survival data, the true survival time for all the subjects is not known, so the mean is not defined.A possible solution to this estimation problem is illustrated by a retrospective cost-effectiveness analysis of the addition of hormonal therapy to standard radiotherapy for patients with locally advanced prostate cancer. A recently proposed method is used to approach the problem caused by censored cost data, and the impact of uncertainty is assessed by bootstrap resampling techniques. Mean survival time is estimated by a restricted means analysis with the time point of restriction determined by statistical criteria. When average total costs and mean survival time is evaluated at this time point of restriction, the result is that the combined therapy (radiotherapy plus hormonal therapy) increases mean survival time by about 1 year, while reducing the costs per patient for the French health insurance system by 12 700 FF. The time point of restriction may also be determined by other criteria and mean survival time may be estimated by extrapolating the survival curves by means of various parametric survival distributions. We show that the exact results of the economic evaluation are decisively determined by the restriction time point chosen and the approach taken to estimate mean survival time.

Neymark N, Adriaenssen I, Gorlia T, Caleo S, Bolla M, Brochon D. · EORTC Health Economics Unit, Avenue E. Mounier 83, bte. 11, B 1200, Brussels, Belgium. · Eur J Cancer. · Pubmed #11549430 No free full text.

Abstract: We present a retrospective cost-effectiveness analysis using data from a randomised controlled trial (EORTC 22863) of the addition of early hormonal therapy with a luteinising hormone-releasing hormone (LHRH) analogue to radiotherapy in the treatment of patients with locally advanced prostate cancer. Data on the use of medical resources were extracted from the hospital charts of 90 patients recruited into the trial by one French hospital. Costs are assessed from the viewpoint of the French healthcare financing system and adjusted for censoring. Expected costs per patient of each treatment is related to the expected outcome, mean survival time, estimated by a restricted means analysis. The time point of restriction is determined by statistical criteria. In the base case analysis with a cut-off time point at 8.58 years, the combined therapy group (COMB) had a gain in mean survival time of 1.06 years (7.05 versus 5.99 years) and a reduction of average total costs of 12700 French francs (FF) (58300 FF versus 71000 FF). The analysis of uncertainty uses bootstrap techniques with 5000 replicates to examine the joint distribution of cost and survival outcomes. In 76% of the cases, COMB results in longer mean survival time and lower costs than the radiotherapy group (RT). In cases where COMB therapy raises costs (13% of the cases), it is rarely by more than 20000 FF per patient, no matter the size of the associated survival gain. It is thus highly likely that COMB should be considered a cost-effective option compared with RT for these patients. The exact result of the economic evaluation is decisively determined by the restriction time point selected for the determination of mean survival time, partly also because the average total costs of the two treatments develop entirely differently as a function of the survival time.