Base bibliographique

Sommaire :

Angiogenèse : l'exemple du cancer rénal
- Réf : Prog Urol, 2008, 18, S309, suppl. S7

VHL gene inactivation, involved in the majority of metastatic non inherited renal carcinoma, I responsible of HIF accumulation. HIF leads to the activation of numerous genes including VEGF and PDGF. VEGF binds to his receptors present on endothelial cells to promote tumoral angiogenesis. Targeted therapy inhibit tumoral blood vessels growth and involves probably others complex mechanisms.

Aspects radiologiques des métastases des cancers urologiques
- Réf : Prog Urol, 2008, 18, S196, suppl. S7

Metastases from cancers in urology do not exhibit specific radiological patterns that would allow identification of the primary site. Their detection relies upon usual imaging techniques, and mainly contrast-enhanced Computed Tomography (CT) that allows the study of the thorax, the abdomen and the pelvis. Ultrasound imaging, and the up-to-date contrast-enhanced ultrasound imaging, as well as Magnetic Resonance Imaging are used in addition to CT in case of contra indication of iodinated contrast agents or for targeted indications (focal liver lesion characterization, MR lymphography for lymph node metastases…). PET CT is playing an increasing role but its performances remain limited for the detection of urological metastases. New anti-angiogenic drugs are questioning the traditional evaluation of the therapeutic response based on RECIST criteria. They require more and more the use of functional imaging techniques, such as MRI or CT dynamic studies as well as contrast-enhanced ultrasound.

Cancer urothéliaux métastatiques : le futur et les perspectives
- Réf : Prog Urol, 2008, 18, S277, suppl. S7

Although bladder cancer is a chemosensitive tumor, results concerning metastatic lesions are poor. Nevertheless, Cisplatin-based chemotherapies are still the treatment of choice. Nowadays, the arrival of new active molecules especially anti-angiogenic drugs incites urooncologists to test their activity on urothelial carcinoma. Furthermore, the development of the concept of individualized treatment through identification of molecular prognostic factors and the application of targeted therapy have gained huge interest.

Chimiothérapies du cancer de prostate métastatique hormonoréfractaire ou hormonorésistant
- Réf : Prog Urol, 2008, 18, S365, suppl. S7

Since 2004 and the first improvement in overall survival in hormone refractory prostate cancer patients (HRPC) brought about by docetaxel, numerous phase II and III studies have been initiated. Considering the lack of efficacy in terms of overall survival, hormonal manipulations such as antiandrogen withdrawal, di-ethylstilbesterol or dexamethason are only indicated in “rising PSA” patients without clinical or radiological evidence of metastases. As first line treatment, the optimal chemotherapy regimen is docetaxel (75mg/m2 every 3 weeks) in association with prednisone (5mg twice daily). Second line chemotherapies (mitoxantron, ixabepilon, docetaxel as a re-treatment, vinorelbin, doxorubicin…) provide modest results only in terms of progression-free survival. A phase III study of Straplatin has been prematurely interrupted.

Targeted anti-angiogenic therapies have shown encouraging results in patients with metastatic localizations, and underline the need to identify target patients early through cellular markers (mTOR or EGFR overexpression) as well as the uselessness of PSA dosage to monitor efficacy. An ongoing phase III study is evaluating bevacizumab in association with docetaxel to improve overall survival. Both the Provenge vaccine and DN 101 (calcitriol) showed a survival gain of a few months in phase III studies. An ongoing EORTC phase II trial is evaluating antisense oligonucleotids in HRPC. Early introduction of docetaxel raises the issue of when to start chemotherapy as it may be relevant to initiate this treatment before the onset of hormone independence. GETUG 15 trial will try to answer this question.

Chirurgie des métastases thoraciques des cancers urologiques
- Réf : Prog Urol, 2008, 18, S250, suppl. S7

Surgery of thoracic metastases from urological malignancies essentially concerns renal carcinoma and non seminomatous testicular germ cell tumors (NSGCT). Complete resection of renal cell cancer lung metastases can be done with low mortality and an appreciable long survival rate, especially for single lesion with a long free interval. For NSGCT, resection of all pulmonary lesions and mediastinal residual masses after chemotherapy affords a very high long term survival rate. In the case of multiple lesions, surgical approaches must be carefully chosen.

Cibles, voies et molécules
- Réf : Prog Urol, 2008, 18, S173, suppl. S7

Human malignancies progress using uncontrolled transduction pathways. Molecules (like VEGF for example) bind to membrane receptors that stimulate transduction pathways (like RAS/MEK/ERK) and activate or inhibit the production of cytoplasmic proteins. Thus it is possible to define targets which can be receptors, molecules or proteins and consequently develop active drugs for targeted therapy.

Comment lire la littérature anglophone d'oncologie médicale ?
- Réf : Prog Urol, 2008, 18, S430, suppl. S7

Peer review of an english oncological paper needs to focus on the principal evaluation criteria. The total of patients is a crucial element to determine the power of the study. This number must be determinated before starting the trial and must be raised at the end before interpreting results. Results and statistical analysis should be evaluated by the reviewer, keeping in mind that the weight of evidence is not correlated to the “p” value.

Douleur et métastases osseuses
- Réf : Prog Urol, 2008, 18, S399, suppl. S7

Average 20% of the cancer patients will have bone metastasis most of time painful and with variable clinical expressions. Due to animal models, the bone metastasis pain is better known and it explains the different treatments mechanisms. After a suitable evaluation of the pain, several therapeutic approaches can be suggested. In addition to the classical analgesics, several medications are known to be efficient in few indications like neuropathic pain. Besides a local surgery, an external radiotherapy or an interventional radiology treatment can often be useful along with a medical treatment. When there is a bone progression, the anti-cancer treatment by chemotherapy, hormonotherapy or targeted therapies must always be reviewed, because if efficient it could have an analgesic action.

Évaluation oncogériatrique du sujet âgé ayant un cancer urologique métastatique
- Réf : Prog Urol, 2008, 18, S415, suppl. S7

The elderly are often the population affected by urologic cancer, especially prostate adenocarcinoma and urothelial tumors. Treatment, especially at the metastatic stage, is the subject of debate due to the problem of iatrogenic consequences compared to potential benefit. A treatment is beneficial when it leads to an increase in the duration and / or quality of life. The evaluation of a patient before treatment should allow estimation of the risk of morbidity, mortality for the patient and treatment should be the tailored to the patient’s physiological condition. The scales of assessment of competitive morbidity and measurement of the level of activity now available provide useful prognostic information to help the urologist to make the best decision concerning the therapeutic approach.

Événements moléculaires impliqués dans le processus métastatique
- Réf : Prog Urol, 2008, 18, S167, suppl. S7

The occurrence of metastasis is probably the least characterised process in tumour progression. It is difficult to study, due to the limited access to metastatic tissues, to the multiple steps involved and the long time required to observe metastasis growth, even in model systems. Our understanding of metastatic processes has been changed in recent years by a number of observations and the development of new concepts.

Gestion des effets secondaires de la suppression androgénique
- Réf : Prog Urol, 2008, 18, S338, suppl. S7

Androgeno-deprivation is the treatment of reference for metastatic prostate cancer but it generates side effects which are too often ignored by physicians due to concentration on hopes of carcinologic benefit. Hot flashes, metabolic syndrome (body mass and lipid changes), decreased libido, erectile dysfunction, anemia, cognitive dysfunction, gynecomastia, decreased muscular mass and osteoporosis are the most frequent symptoms. They can and must be prevented by advice on physical activity and nutrition.

Gestion des toxicités des traitements cibles dans le traitement du cancer du rein métastatique
- Réf : Prog Urol, 2008, 18, S315, suppl. S7

Important advances have been achieved in the treatment of metastatic renal cell carcinoma in the last few years with the targeted therapy. The consequences on the physiological microvasculature could be at the origin of the adverse effects. It seems important for the clinician to know the physiopathology and the management of these toxicities.

Indications de la chimiothérapie dans le traitement des cancers urologiques métastatiques
- Réf : Prog Urol, 2008, 18, S219, suppl. S7

Chemotherapy is useful for many metastatic urological cancer treatments. The main aim is to improve survival and quality of life. Efficacy is directly linked to the type of carcinoma and its chemosensitivity. Very efficient for testis tumors, it is at present the best weapon against metastatic urothelial tumors, especially for transitional cell carcinoma of the bladder. For prostate cancer, chemotherapy is used when metastatic adenocarcinoma has become refractory to hormonal treatment. It is not useful for renal carcinoma. New targeted therapies could soon modify the role of chemotherapy. Thus in clinical trials, some molecules are being tested alone or in association with referent chemotherapies in order to improve results.

Indications de la radiothérapie dans le traitement des métastases des cancers urologiques
- Réf : Prog Urol, 2008, 18, S223, suppl. S7

Radiotherapy is an efficient weapon as part of the treatment of urological carcinoma Metastases. Palliative radiotherapy for bone metastasis has specific caracteristics in Comparison to conventional radiotherapy: rapid initiation, short overall time, efficient and Persistent action and reduced side effects. The indications are often painful symptomatic Lesions. It should be considered as a part of the whole therapeutic schedule for the patient. Generally, this radiotherapy uses a single fraction.

Intérêt du TEP-FDG dans la prise en charge des métastases des cancers urologiques
- Réf : Prog Urol, 2008, 18, S208, suppl. S7

FDG-PET is useful for both topographic and metabolic analysis of metastatic cells. It uses a radioactive metabolite integrated into a molecule which penetrates into the tumoral cells. At present, concerning urologic carcinoma, there is no indication for its use in routine to diagnose primary tumors or to explore their development. However it can be useful for minor recurrences for which CT scan and MRI cannot be conclusive. In particular for kidney and urothelial carcinoma it may represent a diagnostic benefit. Nevertheless, interpretation is often made difficult by tracer urinary excretion. New radio tracers are being tested and will probably lead to new indications. Research on androgen receptors and molecular imaging is ongoing.

L'annonce du diagnostic de métastase : les difficultés psychologiques auxquelles le patient est confronté
- Réf : Prog Urol, 2008, 18, S213, suppl. S7

For the patient learning that there are metastases is frequently comparable to a traumatism. After a period of stupefaction, depression may appear, it must be treated as soon as it is diagnosed. The announcement procedure must favour discussion between patient, pratician and all the health care team. Metastasis announcement management must avoid the patient becoming detached from himself.

L'histoire naturelle du cancer de prostate métastatique
- Réf : Prog Urol, 2008, 18, S327, suppl. S7

Prostate cancer is a pathology which progress with successive stages directly dependant on hormonosensitivity. When metastasis occur, cell modifications and biologic transformations lead to disease diffusion. PSA is useful to practically follow the evolution of the prostate cancer but it is probably the molecular biology which probably will be necessary to get pronostic and predictive markers of metastasis power. At each step of the metastatic cascade, it is possible to imagine a specifique targeted therapy for this disease which is today non curable.

La cascade métastatique : angiogenèse et nouveaux concepts
- Réf : Prog Urol, 2008, 18, S156, suppl. S7

Metastatic progression consists in multiple, progressive, well structured and organized steps, called the metastatic cascade. These steps are becoming clearer, for example, angiogenesis which is absolutely necessary for tumor growth but also for metastatic colonization in the new organ. There are other concepts such as epithelial mesenchymal transition, the premetastatic niche or the metastatic signature theory. They all participate in an irreversible process which escapes from the host control. Tumor progression is highly dependent on genes that mediate the process but also on important extrinsic phenomena such as the tumor microenvironment (basement membranes, the extracellular matrix). The capacity to colonize one organ and not another could be explained by the “seed and soil” theory which postulates that tumor cells (the seed) will only grow in an

Le point sur la scintigraphie osseuse dans les cancers urologiques de l'adulte
- Réf : Prog Urol, 2008, 18, S202, suppl. S7

Bone scintigraphy still is a first line examination to assess bone extension from urological cancers. Technological progress of note has been the arrival of gamma cameras associated with computed tomography with fusion imaging which increases the scintigraphy performance. Nevertheless, bone scintigraphy indications have decreased particularly for the initial assessment of prostate cancer over many years.

Le rôle du pathologiste dans le diagnostic des métastases d'origine urologique
- Réf : Prog Urol, 2008, 18, S178, suppl. S7

Metastases are sometimes the first revelation of urologic cancers. The role of the pathologist in case metastatic disease of unknown origin is to affirm the malignant character of the lesion; provide histological information for possible origins; and to give histological therapeutic arguments. In most of the cases the histological analysis based on cellular morphology is sufficient to suspect a particular origin. In case of poor differentiated carcinoma in addition to the histological analysis, the immunohistochemical study allows the detection of various specific antigens. In this review we approach the various morphological criteria and the interest of the various antibodies to confirm the urologic origin of a metastasis.

Les angoisses de mort et la peur de mourir, l'accompagnement de la fin de vie
- Réf : Prog Urol, 2008, 18, S426, suppl. S7

During metastatic patient follow up, anguish about death is different from the fear of dying. In fact anguish is unconscious and associated with anxiety, on the other hand the fear of dying is a reaction to the threat of imminent death. Physical pain and isolation are factors that increase the pangs of death. The support of friends and family constitutes a real benefit for the treatment of patients during this period.

Les métastases des cancers urologiques : historique, définitions et enjeux
- Réf : Prog Urol, 2008, 18, S143, suppl. S7

The word metastasis came from grec “I move”. Bayle and Récamier were the first to show the relation between a secondary tumor from a primitive carcinoma but it is really Stephen Paget who is the father of the “seed and soil” theory to explain metastasis dissemination. Since, a lot of works have been done to better understand the metastasis physiopathology and in particular Judah Folkman participated very actively in angiogenesis mechanisms research. Today, even if all is not totally understood, physicians know that metastasis is a decisive event in the carcinoma story.

Les métastases des cancers urologiques Rapport 2008 du 102 e congrès de l'AFU
- Réf : Prog Urol, 2008, 18, S141, suppl. S7

Les métastases des cancers urothéliaux : place de la chimiothérapie
- Réf : Prog Urol, 2008, 18, S261, suppl. S7

Chemotherapy is the first line treatment for metastatic urothelial carcinoma. Cytotoxic drugs, in particular cisplatin-based, play an important role in the first line treatment of metastatic patients. Since the 80’s, no drug association has done better than M-VAC (methotrexate, vinblastin, adriamycin et cisplatin) in terms of response rate and 5-year survival rate. The Gemcitabin-Cisplatin (GC) association gives less side effects with similar results. The use of G-CSF (granulocyte/colony stimulating factor) with M-VAC has led to propose a new schedule with dose intensification and better tolerance: M-VAC-HD. In 2008, GC and M-VAC-HD are the two recommended drug associations. Unfortunately, some patients cannot be treated with these toxic drugs, in particular because of Cisplatin toxicity for kidney function. Therefore it is important to continue research to improve tolerance and anti-tumoral efficacy. After failure of first line therapy no consensual drugs exist in the second line, ongoing trials and new agents should increase options in the future.

Les sites métastatiques atypiques des cancers de la prostate
- Réf : Prog Urol, 2008, 18, S357, suppl. S7

The bone tissue is the most frequent site for prostate carcinoma metastasis. Nevertheless many other areas have also been described. Using Pubmed and Cochrane the most exhaustive research possible has been carried out to list these secondary prostate carcinoma lesions.

Les soins de support pour les patients souffrant d'un cancer urologique métastasé
- Réf : Prog Urol, 2008, 18, S410, suppl. S7

Supportive cancer care is defined as “all the care and support necessary for the patient throughout the illness together with specific oncological treatment”. This includes side effect treatments, advice to facilitate access to all therapeutic approaches (i. e. home care) and to keep the patient in the social community. Acute pain centers and palliative care units are at the core of this new approach. In urology, the example of patients with bone metastasis demonstrates the usefulness of this concept. In fact it participates in: antalgic treatment, prevention of bone events (bisphosphonates), adaptation of daily life with a handicap, access to physiotherapy, psychological help. It also includes financial allowances. In France, supportive care centers are being set up in most hospital to facilitate the coordination of all the multidisciplinary teams.

Métastases des cancers du pénis
- Réf : Prog Urol, 2008, 18, S392, suppl. S7

Penile cancer is a rare carcinoma and visceral metastases are uncommon. Metastasis diagnosis is carried out with TDM and MRI but markers can sometimes be helpful (ie SSCAg). There is no referent chemotherapy, a trial has been started (CAVER).

Physiopathologie de la métastase : du primitif au secondaire
- Réf : Prog Urol, 2008, 18, S147, suppl. S7

Metastasis genesis is the result of a series of many steps which make a tumoral cell localised in a primary tumor move and graft onto another organ to form a new tumor. Tumoral cells must go through the following steps: primary tumor formation, proliferation and angiogenesis, deep tissue invasion and arrival in the circulatory system, preparation for travel, migration, embolization in an organ, attachment to the wall of blood vessel, exit from the vessel, adaptation to the micro-surrounding, anchorage and neo-angiogenesis which corresponds to the metastasis establishment. At each step, there are defence and regulation mechanisms which, when they fail, lead to metastatic dissemination.

Physiopathologie, diagnostic et prise en charge des métastases osseuses du cancer de prostate
- Réf : Prog Urol, 2008, 18, S349, suppl. S7

Bone metastasis is very frequent in prostate cancer. Diagnosis is generally easy to make with scintigraphy and it can be confirmed by TDM and RMI. Before metastasis become symptomatic, treatment includes physical and nutritional advice with drugs to prevent bone events (pain, fracture, compression and hypercalcemia). Associated with a effective hormonal treatment, radiotherapy, surgery and analgesics are the principal treatments for symptomatic bone metastasis. Bisphosphonates play a very important role to prevent bone mass loss and to reduce bone complication events. Endothelin inhibitors belong to a new exciting concept to treat these bone metastases, data are needed in order to use them routinely.

Place de l'hormonothérapie dans le traitement du cancer de prostate métastatique
- Réf : Prog Urol, 2008, 18, S332, suppl. S7

Androgen privation is considered as the referent first line treatment for metastatic prostate cancer. Based on LHRH agonist, different therapeutic schedule included maximum androgenic blokage, intermittent treatment and associations with other drugs like oestrogen leading to possible hormonal manipulations. Since metastasis is confirmed, immediate treatment with continue LHRH agonist is the French Association of Urology (AFU) AFU recommendations treatment for metastatic prostate cancer but intermittent treatment can be considered as an option.