[Is there a role for pelvic lymphadenectomy before radiation therapy in localized prostate carcinoma?]. / Faut-il faire un curage ganglionnaire avant la radiothérapie d'un cancer prostatique localisé, et si oui lequel?

Pelvic nodal irradiation has classically been recommended in all patients with a predicted lymph node invasion risk of 15% or greater. However, in view of the results of recent series of extended lymphadenectomy, this rule has been critically discussed. Moreover, the technological progress of radiotherapy has drastically decreased the risk of rectal and urinary injuries secondary to the pelvic irradiation. These two points have lead the teams who used to perform a staging lymphadectomy before radiation therapy in order to avoid a useless pelvic irradiation to the N0 patients, to question this attitude. The objective of this review is to discuss these points and to present the clinical situations in which a pelvic lymphadenectomy performed before the irradiation of a prostate cancer, either exclusive or associated to an androgen deprivation, keeps a potential benefit.

[Choice of optimal margins in prostate conformal radiotherapy]. / Radiothérapie conformationnelle prostatique : quelles marges ?

The planning CT allows the delineation of the prostate (clinical target volume, CTV) but with an imprecision at the apex and the inability to visualize the intraprostatic cancer. MRI enables accurate visualization of the prostate outlines and in some extent the intraprostatic tumour (gross tumour volume [GTV]). The integration of MRI data within the CT remains still complex. Analysis of prostatectomy specimen has guided the definition of a CTV beyond the capsule, depending on pretreatment factors. In practice, the CTV can be defined as follows: prostate-only, for good prognosis tumours; prostate (+0 to 5mm margins, excluding the rectum) and seminal vesicles (possibly limited to 2 cm of their proximal region) for intermediate-risk tumours; prostate (+5mm margins) and seminal vesicles for high-risk tumours. The planning target volume (PTV) should be between 5mm and 10mm depending on the space directions, in the absence of image-guidance (IGRT). It could be reduced to 5mm in case of IGRT. In the adjuvant setting after prostatectomy, the definition of the CTV should follow the recommendations from cooperative groups. It takes into account both the analysis of pattern of local recurrence after prostatectomy, but also the specific histological analysis of the surgical specimen of the patient. The corresponding PTV margin is 6 to 8mm.

Proposal for a predictive model of erectile function after permanent (125)I prostate brachytherapy for localized prostate cancer.

To determine the risk factors for EDin men treated by prostate brachytherapy (PB) for localized prostate cancer and to propose a model to predict post-implant erectile function. Out of a series of 270 sexually active men treated by PB, 241 (89%) (mean age=66 years (range, 43-80)) accepted to participate in a mail-based study on erectile function. The risk factors for erectile dysfunction were determined by regression analysis and a predictive model was proposed. The performance of the model was determined in this population and subsequently verified in a population of 50 men treated by PB in another treatment center. The risk factors for ED after PB were age, the pre-implant IIEF score and prostate volume. In the studied population, the final model to predict a post-treatment IIEF-5 score, using these factors, had a sensitivity of 69% and a specificity of 68% associated to an area under the ROC curve (AUC) of 0.75. The same performance was obtained in another treatment center. Age, pre-implant IIEF-5 score and prostate volume may be used to predict post-implant erectile function in patients treated by PB.

[Prospective economic evaluation of image-guided radiation therapy for prostate cancer in the framework of the national programme for innovative and costly therapies assessment]. / Évaluation économique prospective de la radiothérapie guidée par l'image des cancers de la prostate dans le cadre du programme national de soutien aux thérapeutiques innovantes et coûteuses.

PURPOSE: The main objective of the economical study was to prospectively and randomly assess the additional costs of daily versus weekly patient positioning quality control in image-guided radiotherapy (IGRT), taking into account the modalities of the 3D-imaging: tomography (CBCT) or gold seeds implants. A secondary objective was to prospectively assess the additional costs of 3D versus 2D imaging with portal imaging for patient positioning controls. PATIENTS AND METHODS: Economics data are issued from a multicenter randomized medico-economics trial comparing the two frequencies of patient positioning control during prostate IGRT. A prospective cohort with patient positioning control with PI (control group) was constituted for the cost comparison between 3D (IGRT) versus 2D imaging. The economical evaluation was focused to the radiotherapy direct costs, adopting the hospital's point of view and using a microcosting method applied to the parameters that may lead to cost differences between evaluated strategies. RESULTS: The economical analysis included a total of 241 patients enrolled between 2007 and 2011 in seven centres, 183 in the randomized study (128 with CBCT and 55 with fiducial markers) and 58 in the control group. Compared to weekly controls, the average additional cost per patient of daily controls was €847 (CBCT) and €179 (markers). Compared to PI, the average additional cost per patient was €1392 (CBCT) and €997 (fiducial markers) for daily controls; €545 (CBCT) and €818 (markers) in case of weekly controls. CONCLUSION: A daily frequency for image control in IGRT and 3D images patient positioning control (IGRT) for prostate cancer lead to significant additional cost compared to weekly control and 2D imaging (PI). Long-term clinical assessment will permit to assess the medico-economical ratio of these innovative radiotherapy modalities.

[Dosimetric and clinical benefits of respiratory-gated radiotherapy for lung and breast cancers: results of the STIC 2003]. / Intérêts dosimétriques et cliniques de la radiothérapie asservie à la respiration des cancers du poumon et du sein : résultats du Stic 2003.

PURPOSE: To compare respiratory-gated conformal radiotherapy versus conventional conformal radiotherapy for the irradiation of non-small cells lung cancer and breast cancer. PATIENTS AND METHODS: The STIC 2003 project was a comparative, non-randomized, multicenter and prospective study that included in 20 French centers between April 2004 and June 2008, 634 evaluable patients, 401 non-small cells lung cancer and 233 breast cancers. RESULTS: The final results confirmed the feasibility and good reproducibility of the various respiratory-gated conformal radiotherapy systems regardless of tumour location. The results of this study demonstrated a marked reduction of dosimetric parameters predictive of pulmonary, cardiac and esophageal toxicity, especially for non-small cells lung cancer, as a result of the various respiratory gating techniques. These dosimetric benefits were mainly observed with deep inspiration breath-hold techniques (ABC and SDX), which markedly increased the total lung volume compared to the inspiration-synchronized system based on tidal volume (RPM). For non-small cells lung cancer, these theoretical dosimetric benefits were correlated with a significant reduction in clinically acute and late toxicities, especially the pulmonary. For breast cancer, although less clear due to the lower total dose, there was a decrease in the dose delivered to the heart, potentially reducing the risk of cardiac toxicity in the long-term, especially during the irradiation of the left breast, and a reduction in dose to the contra lateral breast. CONCLUSION: Respiratory-gated radiotherapy appears to be essential to reduce the risk of acute and late toxicities, especially for lungs and heart, during irradiation of non-small cells lung cancer and breast cancers.

[Fertility after prostate brachytherapy with Iode 125 permanent implants for localized prostate cancer]. / Fertilité après curiethérapie par implants permanents d'Iode 125 pour cancer localisé de la prostate.

OBJECTIVES: Preservation of fertility in men of middle age is an issue that is experiencing a growing interest. Prostate cancer is the second most common cancer in men and is diagnosed earlier than before. Brachytherapy is a treatment for prostate cancer that preserves ejaculation. Our aim was to study the fertility of men treated with prostate brachytherapy in order to improve patient information. PATIENTS AND METHODS: In a series of 270 sexually active men with localized prostate cancer treated with brachytherapy (permanent implants of Iode 125) at the Institute Claudius Regaud between 2000 and 2006, mean age 65 years (43-80), four patients spontaneously expressed their interest in the preservation of fertility and had an andrological evaluation. RESULTS: Four patients were aged 43, 48, 57 and 61 years, all working (including two businessmen), their partner was aged respectively 42, 37, 47 and 38 years. All four had a post-treatment semen analysis (done over a year after brachytherapy) rich in spermatozoa, with moderate asthenospermia, the main anomaly being severe hypospermia. These spermiograms were nonetheless consistent with the occurrence of spontaneous pregnancy (occurrence of miscarriage in the patient 1). CONCLUSION: There is an interest in applying to men with prostate cancer their position on fertility in order to inform them about the morbidity of various treatments, options for fertility preservation, and the need to continue a contraception after brachytherapy if the partner is not menopausal.

[Orgasm after curietherapy with permanent iodine-125 radioimplants for localized prostate cancer]. / Orgasme après curiethérapie de prostate par implants permanents d'iode 125 pour cancer localisé de la prostate.

OBJECTIVES: Orgasm is a domain of male sexuality that remains underreported in literature. Our aim was to realize the first detailed analysis of orgasm in patients treated by 125 I permanent prostate brachytherapy for localized prostate cancer. PATIENTS AND METHODS: In a series of 270 sexually active men treated by prostate brachytherapy (125I permanent implantation), 241 (89%), mean age of 65 (43-80), participated in a mailed survey about sexual function after a mean time of 36 months (9-70). Erectile and ejaculatory functions and orgasm were explored using a mailed questionnaire. Two questions focused on orgasm. The first was about quality of orgasm (fast/intense/late, difficult/weak/absent) and the second about the presence of painful orgasm and its frequency (always/sometimes/often). RESULTS: After prostate brachytherapy, 81.3% of sexually active men conserved ejaculation and 90% orgasm. There was a significant deterioration of the quality of orgasm (P=0.0001). More than 50% of the patients had an altered orgasm (weak, difficult, absent) after brachytherapy, vs 16% before implantation (P=0.001). Men with a diminished ejaculation volume often had a weak/difficult orgasm (P=0.007). Neoadjuvant hormonal therapy did not seem to impact the quality of orgasm or the frequency of painful ejaculation. Patients who had an IIEF-5 score higher than 12 had frequently intense orgasm (26.7% vs 2.7%; P<0.001) after brachytherapy. Sixty patients (30.3%) experienced often/sometimes painful ejaculation 12.9% (n=31) before implantation (P=0.0001). CONCLUSION: Most of the patients treated by prostate brachytherapy conserved orgasm after treatment. However, most of the patients described a deterioration of the quality of orgasm.

Male pattern baldness and the risk of prostate cancer.

BACKGROUND: Androgens play a role in the development of both androgenic alopecia, commonly known as male pattern baldness, and prostate cancer. We set out to study if early-onset androgenic alopecia was associated with an increased risk of prostate cancer later in life. PATIENTS AND METHODS: A total of 669 subjects (388 with a history of prostate cancer and 281 without) were enrolled in this study. All subjects were asked to score their balding pattern at ages 20, 30 and 40. Statistical comparison was subsequently done between both groups of patients. RESULTS: Our study revealed that patients with prostate cancer were twice as likely to have androgenic alopecia at age 20 [odds ratio (OR) 2.01, P = 0.0285]. The pattern of hair loss was not a predictive factor for the development of cancer. There was no association between early-onset alopecia and an earlier diagnosis of prostate cancer or with the development of more aggressive tumors. CONCLUSIONS: This study shows an association between early-onset androgenic alopecia and the development of prostate cancer. Whether this population can benefit from routine prostate cancer screening or systematic use of 5-alpha reductase inhibitors as primary prevention remains to be determined.

[PSA kinetics after radiotherapy]. / Cinétique de PSA après radiothérapie.

The prostate specific antigen (PSA) is the best marker of the prostate cancer today although not very specific of this pathology. The dynamic interpretation of this marker always has to prevail over that of overtaking a threshold. After radiotherapy, PSA can decrease after a mean interval of one to two years to a value less than 1 microg/L (predictive of recurrence-free survival). Biochemical recurrence after radiotherapy is defined by an increase of PSA by 2 microg/L or more above the PSA nadir, whether or not it is associated with endocrine therapy. The time of appearance of the recurrence and the PSA doubling time after total radiotherapy have a diagnostic value on the nature of the site of recurrence, local or metastatic.

[Sexual dysfunction after curietherapy and external radiotherapy of the prostate for localized prostate cancer]. / Dysfonctions sexuelles après curiethérapie et radiothérapie externe de la prostate pour cancer de la prostate localisé.

OBJECTIVES: Knowing the importance of sexuality items in the choice by the patient of the modality of treatment of localized prostate cancer, we aimed at reviewing and updating the effects of prostate radiotherapy and brachytherapy on sexual functions. METHOD: A PubMed search was done using the keywords: prostate cancer, erectile dysfunction, radiotherapy, brachytherapy, ejaculation and orgasm. RESULTS: After both radiotherapy and brachytherapy, sexual troubles occur progressively, the onset of occurrence of erectile dysfunction being 12-18 months after both treatments. Even though the pathophysiological pathways by which radiotherapy and brachytherapy result in erectile dysfunction have not yet been fully clarified, arterial damage and exposure of neurovascular bundle to high levels of radiation seem to be two main causes of erectile dysfunction after radiotherapy and brachytherapy. The radiation dose received by the corpora cavernosa at the crurae of the penis may also be important in the etiology of erectile dysfunction. Another important factor following radiotherapy is the treatment modality. Not many data about ejaculation and orgasm after radiation treatments have been published yet. Recent data show that most of the population treated by brachytherapy conserves ejaculation and orgasm after treatment, even if a majority describe reduction of volume and deterioration of orgasm. Patients need to be correctly informed on the possible sequela of radiotherapy and brachytherapy on their sexual well-being while planning their treatment. Patients should also be informed about the possible treatment modalities for erectile dysfunction.

[Pathological stage T3 prostate cancer after radical prostatectomy: a retrospective study of 246 cases]. / Cancer de la prostate de stade pT3 après prostatectomie totale : étude rétrospective de 246 cas.

OBJECTIVE: To determine the survival and prognosis criteria of pT3NxM0 prostate tumours (TNM 2002) after radical retropubic prostatectomy (RRP). MATERIAL AND METHODS: Between 1988 and 2000, 606 consecutive RRP were performed for T1-3 tumours, whose 246 (40.6%) specimens were classified pT3, followed in 53 cases by adjuvant radiotherapy and in 71 cases by salvage radiotherapy. Fifty-five patients received postoperative hormonotherapy at the time of biochemical recurrence. Biochemical recurrence was determined by two PSA values greater than 0.2 ng/ml. RESULTS: Mean age of this group was 65 years at surgery. Mean follow-up was 91.4 months. Mean preoperative PSA was 12.8 ng/ml. Distribution of cases was 170 pT3a (69.1%) and 76 (30,9%). At 10 years, the biochemical progression-free, metastasis-free, specific and overall survival was 54, 86, 92 and 75% respectively. Worse biochemical prognostic factors were lymph node extension, high Gleason score, high preoperative PSA, seminal vesicles involvement, positive surgical margins and adjuvant radiotherapy absence. CONCLUSION: This study shows that pT3 tumours treated with therapeutic associations including RRP presents an excellent specific survival at 10 years. The determination of biochemical recurrence prognostic factors could help to select patients who need complementary treatments after surgery.

[The French preliminary experience of the use of a seed-projector for exclusive iodine 125 prostate brachytherapy: feasibility and acute toxicity]. / L'expérience française de l'utilisation d'un projecteur de source pour la curiethérapie prostatique exclusive par implants permanents d'iode radioactif: faisabilité et données de toxicité aiguë.

PURPOSE: To analyse a new technique for prostate brachytherapy with permanent Iodine implants characterized by the use of a seed projector after a 3D dosimetric peroperative treatment planning (FIRST technique). PATIENTS AND METHOD: 395 patients have been treated in France with this technique in six radiotherapy centres between November 2002 and December 2005 for a localized prostate cancer. RESULTS: Thirteen patients (3.3%) developped a urinary retention, and respectively 7.8 and 26.5% an acute RTOG grade 3 and 2 toxicity. The 6-weeks IPSS score was equal or lower to 15 in 73% with a 11 median IPSS value. A failure of the loading with the seed-projector, leading to a manual loading of the seeds, occurred in 9 patients (2.3%) in two centres, directly related to the loading procedure with the seed-projector in 5 cases. The median duration of the procedure was reduced by 30 minutes for the patients treated in 2005. CONCLUSIONS: This multicenter study establishes the feasibility of the routine use of a seed projector for permanent iodine 125 prostate implants with an initial tolerance similar to the best results published for other implants techniques.

[The impact of 18F-fluorodeoxyglucose positron emission tomography on the 3D conformal radiotherapy planning in patients with non-small cell lung cancer]. / Intérêt de la tomographie par émission de positons au [18F]-fluoro-2-désoxyglucose dans la détermination des volumes cibles de radiothérapie. Application à l'irradiation conformationnelle des cancers bronchiques non à petites cellules.

Traditional radiation treatment planning relies on density imaging such as Computed Tomography for anatomic information of various structures of interest including target and normal tissues. However, the difficulties to distinguish malignant from normal tissue on CT slides often leads to inaccurate outlining of the GTV and/or to geographic misses. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has shown an increase in both sensitivity and specificity over CT in locoregional staging of patients with non-small cell lung cancer (NSCLC). The co registration of FDG-PET images to the data of the CT planning offers the radiation oncologist the possibility to include functional information into the target outlining. For the treatment of patients with NSCLC, it has been shown that the use of FDG-PET images: 1) modified the shape and volume of radiation fields in 22-62% of cases, mainly due to a better nodal staging and distinction of atelectasis from tumor and; 2) significatively reduced the interobserver and intraobserver variability. This paper reviews the results reported in the literature. Challenges and proposed solutions are discussed.

[Nodular bronchioloalveolar carcinoma at early stage]. / Carcinome bronchioloalvéolaire nodulaire de stade IA.

INTRODUCTION: The aim of our study was to describe the main characteristics of bronchioloalveolar carcinoma (BAC) in the light of the latest WHO classification. The clinical, pathological and radiological features of 16 consecutive resected cases of early BAC (stage IA) were reviewed. METHODS: Retrospective pathology of 249 adenocarcinomas over a 32 months period. RESULTS: Computerised tomography (CT) features which supported a diagnosis of BAC included a peripheral location, irregular margins forming a star pattern, pleural tagging, ground-glass attenuation and an air bronchogram. Immunochemistry was positive in all cases for cytokeratins 7 and 19, EMA and TTF-1, but was only variably positive for ACE, P53 and MIB-1. For 14 out of 16 patients clinical outcome was favourable with no evidence to date of recurrence since surgery. Of the others, one developed extra-thoracic metastases and the other a local recurrence requiring further surgery. CONCLUSION: Recognising these characteristics of BAC is important as early diagnosis and treatment of this condition can be associated with an excellent prognosis.

[Standards, options, and recommendation for external radiotherapy of prostatic cancer: evaluation of the effect of dosage]. / Standards, Options et Recommandations pour la radiothérapie externe des patients atteints de cancer de la prostate: évaluation de l'effet dose.

CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical speciality societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the radiotherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC and the French Urology Association (AFU) designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1/ a minimal dose of 70 Gy must be used, whatever the prognostic factors; 2/ it appeared that patients with favourable prognostic indicators (stage T1-2, PSA < or = 10 micrograms/L and Gleason score < or = 6) do not benefit from a dose escalation effect for doses over 70-74 Gy; 3/ patients with intermediate prognosis are the ones who benefit most from the dose escalation effect over 74 Gy, provided they receive exclusive radiation therapy; 4/ whenever possible, patients should be included in controlled trials designed to assess the effects of dose escalation and hormonotherapy.

[Target-volume and critical-organ delineation for conformal radiotherapy of prostate cancer: experience of French dose-escalation trials]. / Délimitation des volumes-cibles et des organes critiques pour la radiothérapie conformationnelle du cancer de la prostate: expérience des essais français d'escalade de dose.

The delineation of target volume and organs at risk depends on the organs definition, and on the modalities for the CT-scan acquisition. Inter-observer variability in the delineation may be large, especially when patient's anatomy is unusual. During the two french multicentric studies of conformal radiotherapy for localized prostate cancer, it was made an effort to harmonize the delineation of the target volumes and organs at risk. Two cases were proposed for delineation during two workshops. In the first case, the mean prostate volume was 46.5 mL (extreme: 31.7-61.3), the mean prostate and seminal vesicles volume was 74.7 mL (extreme: 59.6-80.3), the rectal and bladder walls varied respectively in proportion from 1 to 1.45 and from 1 to 1.16; in the second case, the mean prostate volume was 53.1 mL (extreme: 40.8-73.1), the volume of prostate plus seminal vesicles was 65.1 mL (extreme: 53.2-89), the rectal wall varied proportionally from 1 to 1, 24 and the vesical wall varied from 1 to 1.67. For participating centers to the french studies of dose escalation, a quality control of contours was performed to decrease the inter-observer variability. The ways to reduce the discrepancies of volumes delineation, between different observers, are discussed. A better quality of the CT images, use of urethral opacification, and consensual definition of clinical target volumes and organs at risk may contribute to that improvement.

Trans-rectal ultrasonography (TRUS) with lipiodol injection for localization of the prostatic apex before radiotherapy planning.

PURPOSE: To evaluate reliability of Trans-rectal ultra-sonography (TRUS) guidance with lipiodol injection for prostate localization before radiotherapy planning. MATERIAL AND METHODS: From October 1997 to March 2000, 31 patients with prostatic adenocarcinoma and six patients with anastomotic recurrence after radical prostatectomy had TRUS-guided injection of lipiodol. Two milliliters of lipiodol were injected into each side of the prostate and 1 ml into both seminal vesicles with a 22 Gauge CHIBA needle and US probe guide before radiotherapy planning. We had established a contrast quality index (0 for no prostate enhancement to 5 for efficient pacification without any diffusion). On simulation films, we had performed anatomic measurements for comparison with other anatomic studies. RESULTS: For all 37 patients, TRUS-guided injection was well tolerated. Among 31 patients with the prostate in situ, three had no apex opacification and 15 had no vesicle enhancement or peri-vesicle space diffusion. However, in 19 patients there was good contrast quality with an index score of > or =3. The majority of patients had prostatic apex between 1.5 and 3.5 cm from ischial tuberosities ligne (27 from 28 evaluable for apex). Among 19 evaluable patients, 15 had seminal vesicles 2-4 cm above the top of pubis. For six patients with anastomotic recurrence after radical prostatectomy, lipiodol was precious aid to locate it. We had only one failure because of a precocious bladder absorption relating to a delay which is too long between rectal probe locating and portal films. CONCLUSION: TRUS injection of lipiodol is a simple, inexpensive, relatively safe technique for localization of prostatic apex, but not appropriate for seminal vesicles enhancement. This is also an interesting method to locate anastomotic recurrence.