[Management of testicular teratoma: update by the Oncology Committee of the French Urology Association, section of External Genital Organs (CCAFU-OGE)]. / Prise en charge des tératomes testiculaires: mise au point par le Comité de cancérologie de l'Association française d'urologie groupe organes génitaux externes (CCAFU-OGE).

INTRODUCTION: The objective of this article was to focus on the pathological, clinical and therapeutic aspects of the different forms of testicular teratoma in adults. MATERIAL AND METHODS: The multidisciplinary working group has conducted a literature search on Pubmed with keywords: adult teratoma; malignant transformation; growing teratoma; chemotherapy; surgery with focus on the different forms of adult testicular teratoma. RESULTS: Teratomas of the adults are malignant and subdivided into localized and metastatic forms that may be distinguished under exclusive teratoma form, growing teratoma or teratoma with malignant transformation. The management is based on an enlarged surgical excision (testis and metastasis) with, in metastatic forms, a chemotherapy adjusted with histology. Extended follow-up beyond 10 years is necessary because of the risk of late relapse. CONCLUSIONS: Testicular teratoma is a rare tumor, which is considered malignant with a potential of metastasis. The treatment is based mainly on surgical management.

[CCAFU Recommendations 2013: Penile cancer]. / Recommandations en onco-urologie 2013 du CCAFU : Tumeurs malignes du pénis.

INTRODUCTION: Malignant tumours of the penis are rare tumours. The objective of this article is to propose guidelines for the management of these tumours. MATERIAL AND METHODS: A review of the literature was performed by selecting articles on penile cancer published in PUBMED. RESULTS: The most common histological type is squamous cell carcinoma. Clinical examination of the penis is usually sufficient to assess local extension of the primary tumour, but it can be completed by MRI to assess deeper extension. Inguinal lymph nodes must be systematically palpated on both sides to assess regional extension. In the presence of palpable lymph nodes, aspiration cytology is recommended in combination with abdomen and pelvis computed tomography and (18)F-FDG PET-CT. Sentinel lymph node biopsy is recommended in the case of penile cancer at high risk of lymph node extension with no palpable lymph nodes. Treatment of the primary tumour is usually surgical. It must be as conservative as possible while ensuring negative surgical margins. Brachytherapy or local treatment (laser, cytotoxic cream, etc.) can be proposed in some cases. Bilateral lymph node chains must be systematically treated at the time of diagnosis of the disease. Inguinal lymphadenectomy alone has a curative role in patients with metastatic invasion of a single lymph node (stage pN1). In the case of more extensive lymph node involvement, multimodal management combining chemotherapy, surgery and possibly radiotherapy, must be considered. CONCLUSION: The treatment of penile cancer is usually surgical possibly in combination with chemotherapy in the presence of lymph node extension. The main prognostic factor is lymph node involvement, requiring appropriate management right from the time of diagnosis.

[CCAFU Recommendations 2013: Testicular germ cell cancer]. / Recommandations en onco-urologie 2013 du CCAFU : Tumeurs germinales du testicule.

INTRODUCTION: The objective of this article is to establish guidelines proposed by the external genital organ group of the CCAFU for the diagnosis, treatment and follow-up of the germ cell tumours of the testis. MATERIAL AND METHODS: The multidisciplinary working party studied previous guidelines, exhaustively reviewed the literature, and evaluated references and their level of proof in order to attribute grades of recommendation. RESULTS: The initial work-up of testicular cancer is based on clinical, laboratory (AFP, total hCG, LDH) and imaging assessment (scrotal ultrasound and chest, abdomen and pelvis computed tomography). Inguinal orchidectomy is the first-line treatment allowing characterization of the histological type, local staging and identification of risk factors for micrometastases. The management of stage I tumours must be adapted to the risk by explaining to the patient the benefits/disadvantages of active treatment or watchful waiting as a function of the risk of relapse. Treatment options for stage 1 seminomas comprise : watchful waiting, chemotherapy (1 cycle of carboplatin) or para-aortic radiotherapy. Treatment options for stage 1 nonseminomatous germ cell tumours comprise : watchful waiting, chemotherapy (2 cycles of BEP) or staging retroperitoneal lymphadenectomy. The management of metastatic tumours essentially comprises chemotherapy with 3 or 4 cycles of BEP according to the prognostic group. Radiotherapy may be indicated in seminomas with lymph node metastasis < 3 cm. Review 3 to 4 weeks post-chemotherapy is essentially based on tumour marker assays and chest, abdomen and pelvis computed tomography. Surgical retroperitoneal lymph node dissection is indicated for all residual NSGCT masses > 1 cm and for persistent residual seminoma masses > 3 cm with (18)F-FDG PET-CT uptake. CONCLUSIONS: Germ cell tumours have an excellent survival rate based on precise initial staging, adapted and strictly defined treatment and close surveillance.

[CCAFU's contribution to the French National Cancer Institute's reference frame: Retroperitoneal sarcomas]. / Contribution 2013 du CCAFU au référentiel INCa : Sarcomes du rétropéritoine.

INTRODUCTION: Retroperitoneal sarcomas are rare tumours. The objective of this article is to propose management guidelines. MATERIAL AND METHODS: A review of the literature was performed using the PubMed search engine (1985-2013) with the key words: retroperitoneal sarcoma, prognosis, recurrence, surgery, radiation therapy, chemotherapy. RESULTS: Chest, abdomen and pelvis computed tomography is the reference examination. Other examinations are optional. PET scan is not indicated for the primary diagnosis. CT-guided retroperitoneal biopsy is recommended and must be systematically performed before any management of a suspicious retroperitoneal mass. All retroperitoneal sarcomas must be registered and presented to a multidisciplinary consultation meeting devoted to the management of sarcomas (regional meetings) prior to any therapeutic intervention. Treatment is essentially surgical and is primarily designed to achieve negative surgical margins (R0). Neoadjuvant or adjuvant radiotherapy and chemotherapy can be proposed depending on the risk of progression and the resectability. The recurrence rate is related to tumour grade and surgical margins. The final prognosis is intimately related to the quality of initial management and the number of cases treated by each centre. CONCLUSION: Retroperitoneal sarcomas have a poor prognosis. The quality of initial management directly impacts recurrence-free survival and overall survival. The prognosis is improved by multidisciplinary management conducted in a reference centre.

[CCAFU's contribution to the French National Cancer Institute's reference frame: Adrenal malignant tumors]. / Contribution 2013 du CCAFU au référentiel INCa : Tumeurs malignes de la surrénale.

INTRODUCTION: Malignant tumours of the adrenal gland are adrenocortical carcinomas (ACC), malignant phaeochromocytomas (MPC) or metastatic tumours. The objective of this article is to propose guidelines for the management of these tumours. MATERIAL AND METHODS: A review of the literature was performed by selecting articles on malignant tumours of the adrenal gland published in PUBMED. RESULTS: Abdominal computed tomography is the reference first-line examination. A diameter > 6 cm, a heterogeneous appearance, irregular margins, spontaneous high density (> 20 HU) and delayed wash-out are radiological signs of malignancy. MRI can be used to characterize the tumour with a sensitivity of 89% and a specificity of 99%. Hormone assays and an endocrinology consultation are recommended before any management. When ACC is suspected, (18)FDG-PET is the reference scintigraphic examination, while the isotope of choice for MPC is (18)F-DOPA, which is more sensitive than MIBG. These scintigraphic examinations have a sensitivity close to 100% and allow staging of distant metastases. Percutaneous biopsy has a limited place in the diagnostic work-up. It is only indicated in the case of suspected adrenal metastasis after having excluded phaeochromocytoma and must not be performed in the case of suspected adrenocortical carcinoma. Surgery is first-line treatment for localized and resectable tumours, but is rarely curative due to the high recurrence rate. For ACC, adjuvant therapy by mitotane or adjuvant radiotherapy can be proposed. Metabolic radiotherapy with (131)I-MIBG can be proposed for the treatment of MPC. First-line chemotherapy is indicated in the case of advanced disease or unresectable tumour. Surgical treatment of adrenal metastasis by adrenalectomy is recommended depending on the type and prognosis of the primary cancer. CONCLUSION: Preoperative laboratory, morphological and scintigraphic assessment is essential before any management. First-line treatment is surgical when the tumour is resectable, but must be completed by adjuvant therapy to limit the risk of recurrence.

[Postchemotherapy retroperitoneal lymphadenectomy for testicular cancer. Literature review by the Oncology Committee of the French Association of Urology, External Genitalia Group]. / Lymphadénéctomies rétropéritonéales postchimiothérapie des tumeurs germinales testiculaires. Revue de la littérature par le Comité de cancérologie de l'Association française d'urologie, groupe organes génitaux externes (CCAFU-OGE).

INTRODUCTION: Postchemotherapy retroperitoneal lymphadenectomy (PC RPLDN) leads to an overall survival rate for testicular cancer exceeding 75%. Several questions still persist concerning: preoperative assessment of residual masses, reducing templates of dissection, choosing surgical approaches or including RPLND in high-risk patients' management. METHOD: The main series in the literature of the past 20 years were analyzed and selected to address these issues and reach a consensual diagnostic and therapeutic approach. RESULTS: Forty-eight original articles (1992 to 2011) were selected. They confirm that no preoperative tool can predict the histological nature of residual masses. The unilateral modified template is a valid option for selected patients but the full bilateral dissection remains the standard but more morbid. The laparoscopic approach is being evaluated. The LDNRP PC is indicated in "high risk" situations especially after salvage chemotherapy. CONCLUSION: The bilateral lymphadenectomy by laparotomy of any supracentimeter residual mass, 6 weeks after chemotherapy, for germ cell tumors of the testicle is a standard of care.

[Natural history and management of retroperitoneal sarcoma: Review of the literature by the Oncology committee of the French association of urology]. / Histoire naturelle et prise en charge des sarcomes du rétropéritoine : état des lieux par le comité de cancérologie de l'association française d'urologie sous comité Organes génitaux externes.

INTRODUCTION: The objective of this article of review is to precise the natural history and rules of treatment of retroperitoneal sarcoma. These elements are sometimes ignored of the urologists. MATERIAL AND METHOD: A systematic review of the literature over the 15 last years was carried out on Medline database. RESULTS: The sarcomas of the rétropéritoine are found with diagnosis delay because they don't have specific symptoms. The imagery is sometimes characteristic but only percutaneous biopsy is able to confirm the diagnosis. Retroperitoneal sarcomas are characterized by the high rate of local recurrence, which is related to the survival rate. The main prognostic factors are negative margins and grade of the tumor. The role of adjuvant radiotherapy is limited by the radio sensitivity of the abdominal viscera and the postoperative rehandlings. Today, the role of the neoadjuvant radiotherapy is in evaluation in prospective study. The effectiveness of chemotherapy is limited. CONCLUSION: Complete compartmental surgery without tumor rupture is the cornerstone of treatment. This complex surgery should be performed in a high-volume center.

[Penile cancer in 2010: update from the Oncology Committee of the French Association of Urology: external genital organs group (CCAFU-OGE)]. / Prise en charge du cancer du pénis en 2010 : rapport du forum du Comité de cancérologie de l'Association française d'urologie - organes génitaux externes (CCAFU-OGE).

INTRODUCTION: Treatment of penile carcinoma, even if it is well codified, is not well known because of its rarity. The aim of this article is to report the management of penile carcinoma in 2010. PATIENTS AND METHODS: This article is a summary of the forum of the Committee of Oncology of the French Association of Urology (AFU-CC), held at the Congress of the AFU. RESULTS: The role of the urologist is to diagnose precancerous lesions and penile carcinomas beginners to limit the risk of mutilating treatments. In case of doubt, a biopsy with orientation must be performed. The extension of the tumor is mainly based on clinical examination. Penile MRI can help to assess the depth extension. The treatment of penile tumor must be the most conservative either with surgery or brachytherapy. The risk of local recurrence, after conservative treatment, is 20 % but does not influence survival. The management of lymph nodes should be systematic, bilateral and performed at diagnosis. Tumors greater or equal to pT1b and/or grade greater or equal to 2 are at risk of lymph node extension. The staging of lymph node and distance metastase is clinical and radiological (CT and/or PET-CT 18F-FDG). The inguinal lymphadenectomy have a curative role. The type of inguinal lymphadenectomy (modified and/or total) is based on clinical examination, para-clinical and fine needle aspiration of lymph nodes. In some cases, associated pelvic lymph node dissection is recommended. The place and the type of chemotherapy remain to be defined. This treatment is based at least on the administration of cisplatin. CONCLUSION: The treatment of penile carcinoma requires a local treatment of the tumor as conservative as possible. The management of inguinal lymph nodes is important because of its prognostic value. It must be made at initial diagnosis and is based on clinical and para-clinical examinations.

[Testicular germ cell tumors late relapses]. / Récidives tardives des tumeurs germinales du testicule.

The late relapses (LR) of germinal cells tumors occur by definition more than two years after a succesful initial care. These rare situations have a poor prognosis with a median survival of 23.9 months after chemotherapy. The LR arise as a general rule at the patient's suffering from an advanced initial stage NSGCT. The risk is increased by the arising of a first relapse in the first two years which follow the initial treatment. The diagnosis is mostly mentioned in front of symptoms, CT scan or rising markers in 40% of the cases. The LR group includes two very different clinical situations: the LR of the initially watched GCT, treatment of which bases on the standards of first-line stage II tumor treatment; and the LR of NSGCT after a first line chemotherapy, treatment of which bases mainly on surgery which allows a long-term complete remission in more than 50%. Other situations (multifocal, non extirpable tumors) require therapeutic associations and impact the prognosis. The knowledge of particular genetic profiles could allow in the future to identify the germinal tumors at risk of RT and to propose adapted watching.

[Treatment of lymph nodes in epidermoid carcinoma of the penis: review of literature by the Committee of Cancerology of the French Association of Urology-External Genital Organs Group (CCAFU-OGE)]. / Prise en charge ganglionnaire dans le carcinome épidermoïde du pénis: revue de la littérature par le comité de cancérologie de l'Association française d'urologie-groupe organes génitaux externes (CCAFU-OGE).

INTRODUCTION: Invasive lymph nodes are an independent factor of prognosis and essential for the survival of patients with cancer of the penis. The aim of this article is to analyse published research results on the diagnosis and treatment of lymph nodes in cancer of the penis. MATERIAL AND METHOD: Bibliographic research on Medline was carried out using the terms penile carcinoma, lymph node dissection, lymphadenectomy, survival, chemotherapy and radiotherapy. RESULTS: The risk of lymph node metastasis depends on the stage of the primitive tumour, its histological grade, the presence of venous and lymphatic embolus and the presence of palpable lymph nodes (classification into risk groups by the European Association of Urology [EAU]). A diagnosis of suspected adenopathy based on clinical examination associated with FNA biopsy is essential. No medical imaging (tomodensitometry, NMR, PET-scan) has proven to be superior to clinical examination. The search for the sentinel lymph node although interesting remains to be defined, especially in patients who have no palpated adenopathy but are at risk of metastasis. Not only is surgery on inguinal lymph nodes the only reliable way of confirming an invasive metastatic lymph node, it also plays a therapeutic and prognostic role for patients who have a tumour of the penis which risks spreading to lymph nodes (intermediate or high risk according to EAU). The act should always be two-fold. The type of dissection is in function with the clinical examination: a radical inguinal dissection is recommended in the case of palpated adenopathy and a modified inguinal dissection is recommended if there is no palpated adenopathy, this should be radicalised in the case of metastatic adenopathy on histological examination. Neo-adjuvant or adjuvant chemotherapy would appear to play a interesting role when combined with surgery for certain patients without there being currently being precise consensus because of the lack of documented cases. The same goes for external radiotherapy on inguinal lymph nodes which seems to play a role in local controls of the lymph node disease though increases morbidity risks of surgical intervention. CONCLUSION: Lymph node dissection alone has a therapeutic role in patients who have reached metastasis of lymph nodes (stage pN1). However, it remains insufficient for patients who have metastatic infiltration of more than 2 lymph nodes (stage > or =pN2). Consequently, it would seem important to develop multimodal approaches in the treatment of these patients in order to increase the rate of response to treatment.

[Primary urethral carcinoma. Epidemiology, diagnosis and pathology. Guidelines from the French Urological Association Cancer committee]. / Tumeurs primitives de l'urètre. Epidémiologie, diagnostic et anatomopathologie. Recommandations du comité de cancérologie de l'Association française d'urologie.

Primary urethral carcinomas are unusual. The most frequent histology is the epidermoid carcinoma in both sex, followed by the urothelial carcinoma in men and adenocarcinoma in women. The diagnosis is often late. It is based on a clinical examination under anesthesia and biopsies. MRI is the best imaging modality for the local stadification.

[Histological features and principles of treating testicle tumors in the elderly subject]. / Particularités histologiques et principes de traitements des tumeurs du testicule du sujet âgé.

After the 6th decade, primitive lymphomas are the most frequent tumors of the testis (>30%). They are usually high grade lymphomas that commonly disseminate to the central nervous system. Chemotherapy depends on histological subtype. Germ cell tumors, mainly seminomas, represent less than 20% cases. Therapy do not differ from young adults germ cell tumors. Sex cord stromal tumors, mesenchymal benign tumors, sarcomas and metastasis represent approximately 10% of cases each. The first two are usually cured after orchidectomy. Prognosis of sarcoma is bad. The one of metastasis depends on primitive tumor (prostatic or pulmonary adenocarcinoma or melanoma mainly). Spermatocytic seminoma is a rare and benign tumor, if no sarcomatous component is observed. Mesothelioma are also very rare and of bad prognosis. Other histological subtype are extraordinary rare. This particular histological profile must be in mind when considering the appropriate therapeutic approach of testis tumors in elderly. This work is based on data collected between 1990 to 2005 by the french pathologists of the GELU.

[What about lombo-aortic curage in the treatment of testicle cancer?]. / Que reste-t-il du curage lomboaortique dans le traitement du cancer du testicule?

The indications and techniques of retroperitoneal lymphadenectomy in stage I non seminomatous germ cell tumours have markedly evolved over the past ten years. A literature review allows noticing that historical radical retroperitoneal dissection has been replaced by more limited techniques, known as nerve sparing and nerve preserving lymph node dissection. Stage I non seminomatous germ cell tumours are classified according to the risk of retroperitoneat lymph node involvement; they constitute three groups: low, intermediate and high risk tumours. Retroperitoneal lymph node dissection is considered for low risk patients in case of non compliance or difficult follow-up, and for intermediate risk patients (vascular invasion with presence of high percentage of teratomatous component).

Human prostatic cell line PNT1A, a useful tool for studying androgen receptor transcriptional activity and its differential subnuclear localization in the presence of androgens and antiandrogens.

The human immortalized prostatic cell line PNT1A has been proved to be a good model for analysis of cellular processes such as the prostatic epithelium proliferation in response to androgens and growth factors. Here we used this cell line for studying the transcriptional activity and trafficking of the androgen receptor (AR) by analyzing several actions of antiandrogens. Transient transfection experiments with PNT1A cells were performed with wild type human AR and an androgen-responsive gene reporter. We demonstrated that the transcription of reporter gene could be triggered by natural androgens (testosterone and dihydrotestosterone) in PNT1A cells as well as in the prostatic carcinoma cell line DU-145. With competitive experiments in the two cell lines, we observed no difference between the antagonistic capacity of cyproterone acetate (CPA) and hydroxyflutamide at 10(-7) M. At this concentration, bicalutamide antagonist activity was lower. In parallel, we compared the subcellular localization of the modified green fluorescent protein (EGFP)-AR in COS-7, PNT1A and DU-145 cell lines under fluorescence microscopy: we found different distributions between nucleus and cytoplasm, depending on the cell line and the culture medium. Androgen induced cluster formation within the nucleus of the PNT1A and DU-145 cells. However, the cytonuclear trafficking of androgen bound EGFP-AR in the same living cell and nuclear foci were easier to examine in the PNT1A cells. The antiandrogen capacity of bicalutamide was manifested by a slower androgen-dependent nuclear transfer of EGFP-AR and a homogeneous nuclear localization. A delayed advent of nuclear clusters was observed in presence of CPA. We conclude that the PNT1A cell line is a better model than the DU-145 cell line to analyze the trafficking of AR and the association of AR on the nuclear matrix, as well as to observe the action of antiandrogens on these critical steps in prostate cells.

A stable prostatic bioluminescent cell line to investigate androgen and antiandrogen effects.

We developed a new stable prostatic cell line expressing the human androgen receptor (AR) and the AR-responsive reporter gene to generate a powerful tool for investigating androgen action and for rapid screening of agonists and antagonists. The AR-deficient PC-3 cells were stably transfected with pSG(5)-puro-hAR and pMMTV-neo-Luc. After selection with puromycin and neomycin, one highly inducible clone was isolated and named PALM, for PC-3-Androgen receptor-Luciferase-MMTV. The expression of hAR was confirmed by western blot and steroid-binding assays on the whole cells. The transcriptional activity of the clone was measured after incubation of cells with increasing concentrations of synthetic R1881 or natural androgens (DHT and testosterone). The three agonists had the same maximal activity at 0.1 microM and the fold induction was equal to 20. The agonist and antagonist activities of the steroidal antiandrogens (cyproterone acetate and RU2956) and the non-steroidal antiandrogens (nilutamide, bicalutamide, inocoterone and hydroxyflutamide) measured with the PALM cells were in good correlation with the results obtained with transiently transfected cells. The selectivity in steroid transactivation was demonstrated with estradiol, progesterone, cortisol, dexamethasone and aldosterone. Spironolactone and RU486 showed partial agonist and antagonist activities, whereas R5020 presented only a partial antagonist activity. We here demonstrate that this stable transfectant provides an accurate tool for studying wild-type human AR activation and its regulation by androgens and antiandrogens in a human prostatic epithelial cell, which is routinely available and remains androgen-responsive in vitro.