Feasibility of a tailored operative strategy from organ preservation to pelvic exenteration for cT4 rectal cancer depending on neoadjuvant response.

PURPOSE: Improvements in neoadjuvant therapy for locally advanced cT4 rectal cancer have led to improved tumour response and thus a variety of suitable management strategies. The aim of this study was to report management and outcomes of patients with cT4 rectal cancer undergoing a spectrum of treatment strategies from organ preservation (OP) to pelvic exenteration (PE). METHODS: Patients who underwent elective treatment for cT4 rectal cancer between 2016 and 2021 were included. All patients were treated with curative intent. Surgical management was adapted to tumour response. Kaplan-Meier curves were generated to compare 3-year overall survival (3y-OS), local recurrence (3y-LR) and distant metastases (3y-DM) between different strategies. RESULTS: Among 152 patients included, 13 (8%) underwent OP, 71 (47%) TME and 68 (45%) APR/PE. The median follow-up was 31.3 months. Patients undergoing OP had a lower tumour pretreatment (p < 0.001). Compared to patients with TME, those with APR/PE had a higher rate of ypT4 (p = 0.001) with a lower R0 rate (p = 0.044). The 3y-OS and 3y-DM were 78% and 15.1%, respectively, without significant differences. The 3y-LR was 6.6%, and patients with OP had a significantly worse 3y-local regrowth compared to 3y-LR in patients with TME and APR/PE (30.2% vs. 5.4% vs. 2%, p = 0.008). CONCLUSION: cT4 tumours may be suitable for the full spectrum of rectal cancer management from organ preservation to pelvic exenteration depending on tumour response to neoadjuvant therapy. However, careful attention is required in OP as local regrowth in up to 30% of cases reinforces the need for sustained active surveillance in Watch&Wait programmes.

Is there a best timing for benign prostatic hyperplasia surgery?

INTRODUCTION: Treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) has shifted over the last decades, with medical therapy becoming the primary treatment modality while surgery is being reserved mostly to patients who are not responding to medical treatment or presenting with complications from BPH. Here, we aim to to discuss the optimal timing of surgical management of LUTS/BPH. MATERIALS AND METHODS: A literature search was conducted on Pub-Med/MEDLINE database to identify reports published from January 1990 until January 2022 by combining the following MeSH terms: "Lower Urinary Tract Symptoms"; "Prostatic Hyperplasia"; "Prostatic Hyperplasia/therapy"; "Prostatic Hyperplasia/complications"; "Treatment Outcome"; "Time-to-Treatment". Evidence supporting or not early surgical treatment of BPH was examined and reported in a pros and cons form. RESULTS: The "pro early surgery" highlighted the superior efficacy and cost-effectiveness of surgery over medical treatment for BPH, as well as the possibility of worse postoperative outcomes for delayed surgical treatment. The "con early surgery" considered that medical therapy is efficient in well-selected patients and can avoid the serious risks inherent to surgical treatment of BPH including important sexual side effects. CONCLUSIONS: Clinical trials comparing the outcomes for prolonged medical therapy versus early surgical treatment could determine which approach is more beneficial in the long-term in context of the aging population. Until then, both approaches have their advantages and patients should be involved in the treatment decision.

How Immunotherapy Has Redefined the Treatment Paradigm of Metastatic or Locally Advanced Muscle-Invasive Urothelial Bladder Carcinoma.

In the past decade, the therapeutic arsenal for metastatic bladder cancer has expanded considerably, with the development of immune checkpoint inhibitors (ICIs), antibody-drug conjugates such as enfortumab vedotin, and anti-fibroblast growth factor receptor agents. Clinical trials evaluating ICIs as neoadjuvants, adjuvants, or first- or second-line treatments have produced conflicting results. However, first-line therapeutic strategies have been redefined by the recent publication of results from two clinical trials: CheckMate-901, which demonstrated the superiority of combined treatment with nivolumab and chemotherapy in extending overall survival, and EV-302, which demonstrated that combined treatment with pembrolizumab and enfortumab vedotin reduced the risk of death by 53%. In this review, we discuss the role of ICIs, alone or in combination, in bladder cancer management in the metastatic and adjuvant settings in 2024, considering the latest published trials. The potential role of ICIs as neoadjuvants is also discussed.

Improving pre-emptive access to the kidney transplant waiting list between 2017 and 2021: assessment of a regional program in Aquitaine / Amélioration de l'accès préemptif à la liste d'attente de transplantation rénale entre 2017 et 2021 : bilan d'un programme régional en Aquitaine.

Introduction: Pre-emptive access to the kidney transplant (KT) waiting list remains limited in France, with only 3.9% of patients on pre-emptive KT and 5.6% of patients registered at the time of initiation of dialysis. A similar trend was observed in Aquitaine. The aim of this study was to assess the impact of a regional program in terms of access to the waiting list for patients initiating a kidney replacement therapy (KRT). Methods: We included all patients assessed for registration on the list between 2017 and 2020, 2017 being the reference year and 2018 the beginning of the program. Using the CRISTAL and REIN registries, we assessed changes in the number of patients on the list at the time of initiation of dialysis or transplantation. Results: The number of new assessed candidates increased gradually each year from 255 in 2017 to 352 in 2020 (+38%). The number of patients on the list sharply increased in 2018 from 229 in 2017 to 319 in 2018 (+39.3%) and then remained stable. At the initiation of KRT, the proportion of patients registered on the waiting list increased gradually from 7.1% in 2017 to 18.2% in 2020. The proportion of pre-emptive KT remained stable between 2017 and 2021 (around 7%) with a decrease in 2020 (4.6%). Approximately 60% of patients had a contraindication to transplantation throughout the study. Conclusion: This study showed that a regional program aimed at providing better information to healthcare professionals and patients and encouraging rapid assessment of transplant candidates could increase the rate of pre-emptive registration on the KT waiting list for eligible patients over 4 years.

Introduction: L'accès préemptif à la liste d'attente de transplantation rénale (TR) reste limité en France, avec seulement 3,9 % de TR préemptives et 5,6 % de patients inscrits lors de l'initiation de la dialyse. Une tendance similaire était observée en Aquitaine. L'objectif de cette étude était d'évaluer l'impact d'un programme régional en termes d'accès à la liste d'attente chez les patients débutant un traitement de suppléance. Méthodes: Nous avons inclus l'ensemble des patients évalués pour une inscription sur liste entre 2017 et 2020, 2017 étant l'année de référence et 2018 l'année de début du programme régional. Nous avons évalué de façon annuelle, grâce aux registres CRISTAL et REIN, l'évolution du nombre de patients inscrits sur liste lors de l'initiation du traitement de suppléance par dialyse ou transplantation. Résultats: Le nombre de nouveaux candidats évalués a augmenté graduellement chaque année, passant de 255 en 2017 à 352 en 2020 (+ 38 %). Le nombre de patients inscrits sur la liste a fortement augmenté en 2018 passant de 229 en 2017 à 319 en 2018 (+39,3 %), puis est resté stable. À l'initiation du traitement de suppléance, la proportion de patients inscrits a augmenté graduellement passant de 7,1 % en 2017 à 18,2 % en 2020. La proportion de TR préemptive est restée stable entre 2017 et 2021 (environ 7 %) avec une baisse en 2020 (4,6 %). Environ 60 % des patients présentaient une contre-­indication à la transplantation tout au long de cette étude. Conclusion: Cette étude a montré qu'un programme régional visant à mieux informer les professionnels de santé et les patients et favorisant l'évaluation rapide des candidats à la greffe permet d'augmenter en 4 ans le taux d'inscription préemptive sur liste d'attente de TR chez les patients éligibles.

What happens to orgasmic function after surgical benign prostate hypertrophy (BPH) treatments?

INTRODUCTION: The increasing number of subjects with benign prostate obstruction (BPO) has become a worldwide concern. The sexual problem after benign prostate enlargement (BPE) surgery that has received the most attention in the literature is ejaculation disorder. However, there appears to be a change in orgasmic sensation independent of ejaculation retention. The objective of our study is to explore the influence of BPE surgery on orgasmic function. METHODS: We evaluated the prospective, multicenter clinical data of 104 patients undergoing BPE surgery who reported maintaining sexual activity from January 2016 to November 2020. The endpoint of this study was to decipher the percentage of patients with an orgasm disorder as assessed by the difference between pre-and-postoperative question 10 of the IIEF 15 questionnaire. RESULTS: Orgasm function was stable, improved, and degraded in 34% (n=35), 30% (n=31), and 36% (n=38) respectively. A deterioration in orgasm was statistically significant in men who maintained quality ejaculation with retained force preoperatively and a high IIEF15 scale values preoperative of orgasmic function, overall and intercourse patient satisfaction. CONCLUSION: To enable the patient to maintain a satisfying and healthy sex life after any BPE surgery, urologist physicians should know the prevalence of orgasmic side effects after surgical treatment to provide appropriate counseling to patients. LEVEL OF EVIDENCE: Grade 4.

Inhibidores de la Tirosin-Quinasa en el tratamiento del cáncer de vejiga músculo-infiltrante y el cáncer de próstata hormono-refractario / Tirosin kinase inhibitor in the treatment of muscle-invasive bladder cancer and hormone refractory prostate cancer

OBJETIVO: Se sabe que varias proteín-quinasas son activadas en las células tumorales e impulsan el crecimiento y progresión tumoral. En el carcinoma de células renales metastásico, los inhibidores de la tirosin-quinasa (TKIs) han logrado importantes beneficios en progresión libre de enfermedad y supervivencia global. Los TKIs pueden ser también considerados como una prometedora opción de tratamiento en tumores vesicales y prostáticos. Nuestro objetivo fue dar a conocer los artículos más relevantes publicados para confirmar el interés de la utilización de los TKI en el tratamiento de estos tumores.MÉTODOS: Se realizó una busqueda sistemática en PubMed y se revisaron los artículos recuperados. Las palabras clave utilizadas fueron: inhibidor de la tirosin-quinasa, inhibidor de la protein-quinasa, cáncer de próstata hormono-refractario, cáncer de vejiga músculo-infiltrante. Las publicaciones más relevantes de ciencia básica y ensayos clínicos controlados y aleatorizados fueron resumidas y analizadas.RESULTADOS: En cuanto al cáncer de vejiga, el tratamiento TKI es una de las estrategias terapéuticas más estudiadas en el campo de la terapia dirigida. De hecho, se ha sugerido que dirigiendo solamente TK y/o asociándola con quimioterapia citotóxica puede representar una opción prometedora para tratar el cáncer de vejiga localmente avanzado y/o metastásico. En cuanto al cáncer de próstata hormono-refractario (CPHR), los datos recogidos son aún confusos. Los estudios de ciencia básica encontraron una interesante expresión de receptores EGF y VEGF en las células tumorales confirmando la idea de que los TKI podrían resultar eficientes en el CPHR. Sin embargo la mayoría de estudios publicados de fase II encontraron un débil efecto sobre los síntomas y la calidad de vida sin ninguna disminución en los niveles de PSA o en la supervivencia general. CONCLUSIÓN: Los TKIs todavía no han alcanzado en tumores vesicales o prostátivos una eficacia similar a lo que se ha obtenido en el carcinoma renal metastásico. Se necesitan más estudios para establecer el papel de ese enfoque en tumores no renales (AU)

OBJECTIVES: Various protein kinases are known to be activated in cancer cells and drive tumor growth and progression. In metastatic renal cell carcino-ma tyrosine-kinase inhibitors (TKIs) have achieved signifi-cant progression-free and overall survival improvements. For bladder and prostate cancers TKIs may also be con-sidered as a promising treatment option. Our aim was to report the most relevant published articles to support the interest of the use of TKIs in the treatment of bladder and prostate cancer.METHOD: PubMed database and bibliographies of retrieved articles were reviewed. The key words used were tyrosine-kinase inhibitor, protein-kinase inhibitor, hormone refractory prostate cancer, muscle invasive bladder cancer. The most relevant publications from ba-sic science and clinical randomized controlled studies were summarized and analyzed.RESULTS: Regarding bladder cancer, TKI treatment is one of the most studied therapeutic strategies in the field of targeted therapy. Indeed, it has been suggested that targeting TK alone and/or in association with cytotoxic chemotherapy may represent a promising option for treating locally advanced and/or metastatic bladder cancer. Concerning hormone refractory prostate cancer (HRPC), collected data are still confusing. Basic scien-ce studies found an interesting expression of EGF and VEGF receptors on cancer cells supporting the idea that TKIs could be efficient in HRPC. Nonetheless most of published clinical phase II studies found a weak effect on symptoms and quality of life without any decrease in PSA levels or overall survival.CONCLUSION: TKIs have not yet achieved in bladder and prostate cancers similar efficacy to what has been obtained in metastatic renal cell carcinoma. Further stu-dies are needed to establish the place of such an appro-ach in non renal tumors(AU)