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La déprivation androgénique (ADT) dans le cancer de la prostate (CaP) est associée à une perte de la masse osseuse et une diminution de la force musculaire exposant aux risques de chutes et de fractures. Bien que les recommandations internationales suggèrent d'effectuer une densitométrie osseuse (DMO) au début du traitement, moins de 10 % des patients le font. La mise en œuvre d'un parcours de soins pourrait contribuer à prévenir les complications osseuses sous ADT. L'objectif de ce parcours-patient est d'améliorer le dépistage de la fragilité osseuse chez les patients initiant une hormonothérapie pour un CaP. Les urologues, oncologues et radiothérapeutes issus d'un même centre hospitalo-universitaire ont systématiquement adressé dans notre service tous les patients débutant une hormonothérapie pour un CaP pour une évaluation osseuse comprenant une DMO, une analyse biologique et une consultation spécialisée de rhumatologie. L'efficacité du parcours a été estimée sur le nombre de patients ayant effectué une DMO au début de l'ADT. Entre mars et décembre 2022, 116 des 119 patients (97 %) adressés à notre service ont pu bénéficier d'un bilan osseux dans un délai moyen de 36 ± 15 jours. L'âge moyen à la première consultation était de 75 ± 7 ans, l'IMC moyen de 26,9 ± 4,7 kg/m2, 56 % étaient des fumeurs anciens ou actuels et l'indice de comorbidité de Charlson était de 4,75 ± 2,5 avec 20 % de diabète, 15 % de maladies vasculaires périphériques, 11 % de coronaropathie et 10 % d'insuffisance rénale chronique. En ce qui concerne le CaP, 65 % des patients étaient à un stade localisé ou localement avancé tandis que 35 % étaient métastatiques et, 44 % présentaient un score histo-pronostique de cancer de haut risque (ISUP 4 ou 5). Soixante-quatre patients (55 %) ont été programmés pour une radiothérapie externe prostatique concomitante de l'ADT, comme traitement initial ou de rattrapage après prostatectomie radicale. Le taux médian de PSA au moment du diagnostic était de 16 ng/mL (8,8–38,5). À l'inclusion, 70 % des patients avaient un CaP nouvellement diagnostiqué, tandis que 30 % avaient un CaP en rechute. L'ADT a été prescrite seule pour 65 % des patients ou en association avec une hormonothérapie de nouvelle génération (HTNG) pour 35 % des patients et 26 % avec une corticothérapie concomitante avec une dose moyenne de 10 ± 4 mg. La durée moyenne de l'ADT était de 16 ± 20 mois. Concernant les complications osseuses, 11 % des patients avaient déjà fait au moins une fracture, principalement au rachis, 15 % avaient des antécédents familiaux de fracture de la hanche et 20 % avaient fait une chute au cours de l'année écoulée. Quarante-deux pour cent des patients avaient reçu une supplémentation en vitamine D, mais un seul avait déjà été traité avec un agent anti-ostéoporotique. Finalement, 114 patients ont bénéficié d'une DMO. Un T-score ≤ −2,5 au rachis lombaire a été observé pour 9 patients et un T-score ≤ −2 pour 17 patients. À la hanche, un T-score ≤ −2,5 a été retrouvé pour 12 patients et T-score ≤ −2 pour 35 patients. Un score T ≤ −2,5 à au moins un site a été retrouvé chez 18 patients (16 %) et T-score ≤ −2 pour 41 patients (35 %). Après évaluation globale, un traitement anti-ostéoporotique a été prescrit chez 40 % des patients par bisphosphonate (71 %) ou dénosumab (29 %). Ce parcours de soins a permis à 97 % des patients de bénéficier d'une évaluation osseuse au début de l'ADT pour un CaP. Cette cohorte de 116 patients confirme la forte prévalence d'une masse osseuse basse dans cette population, d'où la nécessité de la dépister et de proposer un traitement anti-ostéoporotique afin de prévenir les complications osseuses. [ABSTRACT FROM AUTHOR]

Résumé L’immunothérapie des cancers a longtemps représenté une option thérapeutique marginale en cancérologie en dépit de forts arguments documentant le rôle du système immunitaire dans le contrôle de la prolifération des cancers. Les succès récents de l’immunothérapie résultent du fait que l’objectif n’est plus uniquement d’activer le système immunitaire contre les cellules tumorales, mais de tenir compte également du microenvironnement immunosuppresseur induit par la tumeur. Parmi ces mécanismes, les molécules de costimulation inhibitrices (CTLA-4, PD-1, etc.) exprimées par les lymphocytes T dans le stroma des tumeurs pourraient expliquer leur manque d’efficacité à inhiber la croissance tumorale. L’inhibition de l’interaction de ces molécules avec leurs ligands (CD80, PD-L1, etc.) a permis de réactiver ces lymphocytes T anti-tumoraux. Sur le plan clinique, l’administration de l’anticorps anti-CTLA-4 (ipilimumab : Yervoy ® ) a obtenu une autorisation de mise sur le marché pour les patients atteints de mélanomes métastatiques. Les anticorps anti-PD-1 (nivolumab : Opdivo ® , pembrolizumab : Keytruda ® ) ont démontré leur efficacité par comparaison au traitement de référence dans les mélanomes métastatiques, les cancers du poumon avancés et les cancers du rein métastatiques. Dans des essais de phase I et II, une efficacité de ces traitements a également été observée dans d’autres tumeurs (maladie de Hodgkin, cancers de la tête et du cou, cancer de la vessie, cancer de l’estomac, etc.). Ces traitements ont été associés à l’apparition d’effets secondaires de type auto-immun prévisibles de par la levée du frein sur le système immunitaire induit par ces molécules. La recherche de biomarqueurs associés à ces traitements constitue un enjeu d’avenir pour cette nouvelle classe thérapeutique. Cancer immunotherapy has occupied a marginal therapeutic option in cancer despite strong arguments documenting the role of the immune system in controlling the proliferation of cancers. The recent success of immunotherapy results from a change in the past paradigm. From now on, the goal is not only to activate the immune system against tumor, but also to take account of the immunosuppressive tumor microenvironment Among these mechanisms, negative costimulatory molecules (CTLA-4, PD-1, etc.) expressed by T cells in the tumor could explain their lack of effectiveness in inhibiting tumor growth. Blocking these molecules allowed the reactivation of anti-tumor T cells. Clinically, the administration of anti-CTLA-4 antibody (ipilimumab: Yervoy ® ) was granted marketing authorization for patients with metastatic melanoma. The anti-PD-1 antibodies (nivolumab: Opdivo ® , pembrolizumab: Keytruda ® ) have demonstrated clinical efficacy when compared to the standard therapy in metastatic melanomas, advanced lung cancers and metastatic renal cell carcinoma. In phase I and II clinical trials, other tumors (Hodgkin's disease, head and neck cancers, bladder cancer, gastric cancer, etc.) appear to be responsive to these immunomodulators. These treatments were associated with the occurrence of side effects dominated by autoimmunity predictable by unlocking the breaks exerted by immune system to maintain tolerance against self-antigen. The optimization of therapeutic combination based on these molecules and the search for biomarkers associated with these treatments constitute a challenge for the future for this new therapeutic class of drugs for oncology. [ABSTRACT FROM AUTHOR]

Castration-resistant metastatic prostate cancer remains lethal and a therapeutic challenge. Current strategies are geared towards the personalization of treatments based on the identification of relevant molecular targets, including genomic alterations involved in tumoral processes. Among these novel targeted therapies, poly-ADP-ribose polymerase inhibitors (PARPi), by blocking the action of enzymes involved in deoxyribonucleic acid (DNA) repair, induce the destruction of cells carrying defects in homologous recombination repair, often associated with alterations in genes involved in this mechanism. Thus, determining the presence of a molecular anomaly, particularly alterations in the BRCA1/2 genes, is a prerequisite for initiating PARPi monotherapy. In patients with metastatic castration-resistant prostate cancer , around 20-30 % carry this type of mutation. In this population, single-agent studies have demonstrated PARPi ability to prolong overall survival, and to improve symptom control, including pain. Other studies are underway to assess their effectiveness in combination with other therapies, and it already appears that association with new-generation hormone therapy can further prolong radiological progression-free survival, regardless of the mutation status of the genes involved in DNA repair, indicating a synergistic action between PARPi and new-generation hormone therapy., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Collecting duct carcinoma (also known as Bellini tumour) and renal medullary carcinoma are two extremely rare and aggressive renal cancers. They are both less responsive to conventional treatments used in clear cell renal carcinoma. There are very few studies evaluating their optimal management and currently, at the metastatic stage, polychemotherapy based on platinum salts remains the most widely used. The emergence of new treatments such as anti-angiogenic TKIs, immunotherapy or treatments targeting specific genetic abnormalities, opens up a new field of possibilities in the management of these cancers. The evaluation of the response to these treatments is therefore essential. In this article, we will review the status of their management and the various studies that have evaluated recent treatments in these two cancers., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The standard of care for metastatic clear cell renal cell carcinoma (mccRCC) has changed dramatically over the past decades thanks to the increasing number of treatments: anti-VEGFR tyrosine kinase inhibitors (TKI), mTOR inhibitors and immune checkpoint inhibitors (ICI): anti PD(L)-1 used as monotherapy or in combination with anti CTLA-4 or anti angiogenic therapies. In the face of rising therapeutic options, the question of the therapeutic sequences arises: which treatment for which patient? Actually, there is a lack of predictive biomarkers. A greater understanding of the cancer biology and its interaction with the microenvironment has allowed the development of genomic signatures which could perhaps be used as predictive biomarker. This review will give an insight on some robust genomic signatures assessed in mccRCC and will have a closer look at BIONIKK phase II trial, which is the first trial to adapt treatments according to the molecular characteristics of the tumor in the context of mccRCC., (Copyright © 2020 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)

Immunotherapy for Renal Cell Carcinoma: Clear cell kidney cancer is a tumour type whose development and progression is driven by the HIF/VEGF angiogenesis pathway. Anti-angiogenic (AA) agents, particularly anti-VEGFR tyrosine kinase (TKI) inhibitors, have profoundly modified the prognosis of patients in the metastatic setting (mRCC) since their registration in 2006. At the same time, mTOR inhibitors have also brought significant benefit to patients. More recently, treatments restoring adaptive anti-tumor immunity, anti-program death 1 (anti-PD-1) checkpoint inhibitors (ICP), have in turn revolutionized the management of patients with mRCC. The multi-tumor efficacy of these ICPs proves the crucial role of anti-tumor immunity in tumor development and progression in a number of tumors including clear cell kidney tumours (ccRCC). The tumor immune microenvironment (TME) of ccRCC is known to be highly immunosuppressive. Thus ccRCCs are characterized by a strong infiltration of CD8+ T lymphocytes, frequently expressing immunological checkpoint molecules on their surface, giving them a poor prognostic feature. These characteristics partly explain the effectiveness of ICP in ccRCC and constitute a strong rationale for their further development, either at an earlier stage or in combination, particularly with AA or TKI. In this review are compiled the main clinical results of immunological checkpoint molecules alone or in combination in 1 st line or after TKI failure., (© 2018 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)

Competing Interests: S. Oudard déclare des liens ponctuels avec Astellas, Bayer, Janssen et Sanofi. M. Velev et Y. Belhadj déclarent n’avoir aucun lien d’intérêts. C. Thibault et Y. Vanno déclarent des liens ponctuels avec Astellas, Janssen et Sanofi.

T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis. Tim-3 recently appeared as a potential biomarker of anti-PD-1 resistance. Combined blockade of PD-1 and Tim-3 axis demonstrated potent clinical efficacy in preclinical models and reinforced the rationale of using an anti-Tim-3 to override tumor resistance., (© 2018 médecine/sciences – Inserm.)

Immunotherapy in Uro-Oncology: Immunotherapy is moving forward in prostate cancer. The autologous vaccine, Sipuleucel-T has been the first vaccine to be approved by FDA. First results with GVAX, tasquinimob or anti-PD-1 have been disappointing. Ipilimumab seen to be more active at an earlier stage of prostate disease. Identifying predictive factor or surrogate markers of activity of immunotherapy and which agents are clinically effective alone or in combination with others therapies such as hormonal or bone targeted therapies are warranted., (© 2016 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)

Cancer immunotherapy has occupied a marginal therapeutic option in cancer despite strong arguments documenting the role of the immune system in controlling the proliferation of cancers. The recent success of immunotherapy results from a change in the past paradigm. From now on, the goal is not only to activate the immune system against tumor, but also to take account of the immunosuppressive tumor microenvironment Among these mechanisms, negative costimulatory molecules (CTLA-4, PD-1, etc.) expressed by T cells in the tumor could explain their lack of effectiveness in inhibiting tumor growth. Blocking these molecules allowed the reactivation of anti-tumor T cells. Clinically, the administration of anti-CTLA-4 antibody (ipilimumab: Yervoy ® ) was granted marketing authorization for patients with metastatic melanoma. The anti-PD-1 antibodies (nivolumab: Opdivo ® , pembrolizumab: Keytruda ® ) have demonstrated clinical efficacy when compared to the standard therapy in metastatic melanomas, advanced lung cancers and metastatic renal cell carcinoma. In phase I and II clinical trials, other tumors (Hodgkin's disease, head and neck cancers, bladder cancer, gastric cancer, etc.) appear to be responsive to these immunomodulators. These treatments were associated with the occurrence of side effects dominated by autoimmunity predictable by unlocking the breaks exerted by immune system to maintain tolerance against self-antigen. The optimization of therapeutic combination based on these molecules and the search for biomarkers associated with these treatments constitute a challenge for the future for this new therapeutic class of drugs for oncology., (Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Aim: The aim of this literature review was to focus on the new highlights regarding oncologic and safety outcomes depending on the type of castration used., Material: Literature search using various algorithms "prostate cancer", "castration", "agonist", "antagonist", "orchiectomy", "GnRH", "FSH", "androgen deprivation therapy" has been performed in April 2015, through the PubMed and Embase databases., Results: GnRH agonists and antagonists are both currently used in clinical practice. Nevertheless, differences regarding their pharmacologic properties have been highlighted in recent studies, specifically regarding the rapidity, sustainability and depth of the castration, but also the decrease in FSH level. Such differences may have oncological impact on the patient, regarding the disease biological control and the time to progression, and a tolerability impact, especially on the cardiovascular risks. The role of the depth and the sustainability of the castration in one hand, the FSH impact in the other hand, as well as a direct inhibition on extra-pituitary GnRH receptors by antagonist might explain these differences., Conclusions: Recent studies suggest differences between GnRH agonists and antagonist that could impact the patient clinical outcomes. However, further high level of evidence comparative studies remains warranted., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: The potential prognostic value of hypertension and proteinuria of anti-vascular endothelial growth factor (VEGF) drugs has not been assessed in routine clinical practice so far in breast cancer. The objectives of the MARS study were to assess the prevalence of proteinuria and hypertension at baseline, their incidence under anti-VEGF treatment, and to evaluate a possible link with overall survival., Methods: Patients from 8 centres were included between 2009 and 2011 with a follow-up of 1 year. They were naive of any previous anti-VEGF treatment and planned to be started on one. The results of the group of patients with breast cancer receiving bevacizumab are presented., Results: Four hundred and two patients with breast cancer and treated with bevacizumab were included. At inclusion, hypertension prevalence was 12.4%, proteinuria 23.9%. The incidence of de novo proteinuria and hypertension during the follow-up was 61.7% and 16.8%, respectively. Among patients with de novo proteinuria, 62.2% afterwards improved/normalized. No thrombotic microangiopathy was reported. Baseline or de novo proteinuria/hypertension were not associated with overall survival in breast cancer patients treated with bevacizumab., Discussion: These results on the renovascular safety of bevacizumab in breast cancer patients showed that the prevalence of hypertension and proteinuria was high at baseline and, moreover, patients treated with bevacizumab frequently developed de novo hypertension and/or proteinuria. Finally, neither hypertension, nor proteinuria, neither at baseline, nor de novo, were associated with overall survival in our cohort of "real-life'' patients

Objective: Describe the implementation and preliminary results of the “Experimental Program Personalized care” in patients with Head and Neck cancer., Materials and Methods: After being selected a graduate nurse status, called coordination, participated in the development of forms of detection needs and concerns of patients, in collaboration with various health professionals., Results: Between January 2011 and December 2012, 200 new patients with head and neck cancer were included: 62% with advanced cancer and 38% of early stage. No patient refused to participate in this experiment. At least one consultation with a psychiatrist was necessary for 82% of patients with advanced cancer. Social problems were the second axis of the needs of patients., Conclusion: By identifying the needs of patients and organizing their support, this evaluation optimizes not only the therapeutic care for the patient but also the management of human resources within the team.

The management of a patient with cancer, including lung cancer requires the investment of many health caregivers. The development of surgical techniques as well as targeted therapies requires a specialization of each. In order to optimize the actions of each, coordination of support is required from the diagnosis of cancer. This coordination can reduce iatrogenic toxicity and improve quality of life during the disease. It may also enhance quality of accompaniment of the patient, his family and a fortiori the health care team. The development of this coordination of supportive care in oncology, as part of a department of cancerology including care of patients with lung cancer is described. This organization allows to limit the toxicities of cancer treatment, but also to improve the suffering of patients by focusing on maintaining the patient at home., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)