Is trimodal therapy the current standard for muscle-invasive bladder cancer?

OBJECTIVE: The aim of this review is to summarize the current evidence and future perspectives of bladder-sparing treatment for MIBC. METHODS: A non-systematic literature search in Medline/Pubmed was performed in October 2023 with the following keywords "bladder cancer", "bladder-sparing", "trimodal therapy", "chemoradiation", "biomarkers", "immunotherapy", "neoadjuvant chemotherapy", "radiotherapy". RESULTS: Urology guidelines recommend radical cystectomy as the standard curative treatment for muscle-invasive urothelial bladder cancer, reserving radiotherapy for patients who are unfit or who want to preserve their bladder. Given the morbidity and mortality of cystectomy and its impact on quality of life and bladder function, modern oncologic therapies are increasingly oriented toward organ preservation and maximizing functional outcomes while maintaining treatment efficacy. Trimodal therapy, which incorporates maximal transurethral resection followed by radiotherapy with concurrent radiosensitizing chemotherapy, is an effective regimen for bladder function preservation in well-selected patients. Despite the absence of comparative data from randomized trials, the two approaches seem to provide comparable oncologic outcomes. Studies are evaluating the expansion of eligibility criteria for trimodal therapy, the optimization of radiotherapy and immunotherapy delivery to further improve outcomes, and the validation of biomarkers to guide bladder preservation. CONCLUSIONS: Trimodal therapy has shown acceptable outcomes for bladder preservation; therefore, it provides a valid treatment option in well-selected patients.

Management of oligometastatic/metastatic sarcomas and place of local treatments with focus on modern radiotherapy approaches.

Soft tissue sarcomas are a rare and heterogeneous disease. For localized disease, treatment is based on surgery and radiotherapy with or without chemotherapy depending on risk factors. Upfront metastases are present in 7 to 20% of cases, and are localized to the lungs in most of cases. Disseminated disease is generally considered incurable but in selected cases, aggressive local treatment of metastases allowed long survival. Treatment of primary tumour is often debated. Our purpose is to evaluate the literature concerning the role of radiotherapy in the management of primary metastatic soft tissue sarcomas.

The role of radiation therapy for de novo metastatic bladder and renal cancers.

Metastatic bladder and renal cancers account respectively for 2.1% and 1.8% of cancer deaths worldwide. The advent of immune checkpoint inhibitors has revolutionized the management of metastatic disease, by demonstrating considerable improvements in overall survival. However, despite initial sensitivity to immune checkpoint inhibitors for most patients, both bladder and renal cancer are associated with short progression-free survival and overall survival, raising the need for further strategies to improve their efficacy. Combining systemic therapies with local approaches is a longstanding concept in urological oncology, in clinical settings including both oligometastatic and polymetastatic disease. Radiation therapy has been increasingly studied with either cytoreductive, consolidative, ablative or immune boosting purposes, but the long-term impact of this strategy remains unclear. This review intends to address the impact of radiation therapy with either curative or palliative intent, for synchronous de novo metastatic bladder and renal cancers.

Indication and perspectives of radiation therapy in the setting of de-novo metastatic prostate cancer.

Prostate cancer is the most common cancer and the third leading cause of cancer mortality in men. Each year, approximately 10% of prostate cancers are diagnosed metastatic at initial presentation. The standard treatment option for de-novo metastatic prostate cancer is androgen deprivation therapy with novel hormonal agent or with chemotherapy. Recently, PEACE-1 trial highlighted the benefit of triplet therapy resulting in the combination of androgen deprivation therapy combined with docetaxel and abiraterone. Radiotherapy can be proposed in a curative intent or to treat local symptomatic disease. Nowadays, radiotherapy of the primary disease is only recommended for de novo low-burden/low-volume metastatic prostate cancer, as defined in the CHAARTED criteria. However, studies on stereotactic radiotherapy on oligometastases have shown that this therapeutic approach is feasible and well tolerated. Prospective research currently focuses on the benefit of intensification by combining treatment of the metastatic sites and the primary all together. The contribution of metabolic imaging to better define the target volumes and specify the oligometastatic character allows a better selection of patients. This article aims to define indications of radiotherapy and perspectives of this therapeutic option for de-novo metastatic prostate cancer.

[Early detection of prostate cancer: Towards a new paradigm?] / Détection précoce du cancer de la prostate : vers un nouveau paradigme ?

Prostate cancer (PCa) is a public health issue. The diagnostic strategy for PCa is well codified and assessed by digital rectal examination, PSA testing and multiparametric MRI, which may or may not lead to prostate biopsies. The formal benefit of organized PCa screening, studied more than 10 years ago at an international scale and for all incomers, is not demonstrated. However, diagnostic and therapeutic modalities have evolved since the pivotal studies. The contribution of MRI and targeted biopsies, the widespread use of active surveillance for unsignificant PCa, the improvement of surgical techniques and radiotherapy… have allowed a better selection of patients and strengthened the interest for an individualized approach, reducing the risk of overtreatment. Aiming to enhance coverage and access to screening for the population, the European Commission recently promoted the evaluation of an organized PCa screening strategy, including MRI. The lack of screening programs has become detrimental to the population and must shift towards an early detection policy adapted to the risk of each individual.

[Relationship between doses to anatomical structures and erectile dysfunction after radiotherapy for prostate cancer: A systematic review]. / Relations entre doses dans les structures anatomiques et dysfonction érectile après radiothérapie pour un cancer de la prostate : revue systématique de la littérature.

PURPOSE: During prostatic radiotherapy, damage to several anatomical structures could be the cause of erectile dysfunction: corpora cavernosa, internal pudendal arteries, penile bulb, and neurovascular bundles. Numerous studies have analysed the correlations between the dose received by these structures and erectile function. The objective of this article is to make a systematic review on current knowledge. MATERIALS AND METHODS: A systematic review was performed in the Medline database using the search engine PubMed. Keywords for the search included: erectile dysfunction, penile bulb, corpora cavernosa, cavernosum, neurovascular bundles, radiation therapy, cancer, prostate cancer. The selected articles must study a correlation between erectile dysfunction and the dose received by anatomical structures. A total of 152 articles were identified. Of these 152 articles, 45 fulfilled the defined selection criteria. RESULTS: For corpora cavernosa, seven studies were identified, only two studies demonstrated a significant correlation between the dose received by corpora cavernosa and the occurrence of erectile dysfunction. For penile bulb, only 15 of 23 studies showed a correlation. A mean dose on the penile bulb greater than 20Gy was found to be predictive of erectile dysfunction. None of the eight trials concerning neurovascular bundles succeeded to show a correlation between dose and erectile dysfunction. Only one study evaluated the relationship between the dose received by internal pudendal arteries and erectile dysfunction but was found to be negative. However, vessels-sparing studies showed good results on erectile function preservation without compromising the target volume. CONCLUSION: We currently have little data to show a correlation between erectile dysfunction and sexual structures. It would be necessary to have additional prospective studies evaluating the impact of an optimization on these sexual structures on erectile dysfunction.

French AFU Cancer Committee Guidelines - Update 2022-2024: prostate cancer - Diagnosis and management of localised disease.

OBJECTIVE: The objective of the French Urology Association Cancer Committee is to propose an update of the recommendations for the diagnosis and management of prostate cancer (PC). METHODS: A systematic review of the literature from 2020 to 2022 was conducted by the CCAFU on the diagnosis and therapeutic management of localised PC, while evaluating the references and their levels of evidence. RESULTS: The recommendations specify the genetics, epidemiology and means of diagnosing prostate cancer, as well as the notions of screening and early detection. MRI, the gold standard imaging examination for localised cancer, is recommended before prostate biopsies are performed. The transperineal approach reduces the risks of infection. The therapeutic methods are described and recommended according to the clinical context. Active surveillance is the gold standard of treatment for tumours with a low risk for progression. Early salvage radiotherapy is recommended in case of biochemical recurrence after radical prostatectomy. Imaging, particularly molecular imaging, helps to guide the decision-making in the event of biochemical recurrence after local treatment, but should not delay early salvage radiotherapy in the event of biological recurrence after radical prostatectomy. CONCLUSION: This update of the French recommendations should help to improve the management of patients with PC.

French AFU Cancer Committee Guidelines - Update 2022-2024: prostate cancer - Management of metastatic disease and castration resistance.

OBJECTIVE: The objective of the French Urology Association Cancer Committee is to propose an update of the recommendations for the management of prostate cancer. METHODS: A systematic review of the literature from 2020 to 2022 was conducted by the CCAFU on the elements of therapeutic management of metastatic and castration-resistant prostate cancer (PC), while evaluating the references and their levels of evidence. RESULTS: Androgen deprivation therapy (ADT) remains the standard treatment for metastatic prostate cancer. ADT intensification is now a standard of care in the management of metastatic prostate cancer. This intensification is discussed in relation to the patient and the characteristics of the disease. For all metastatic hormone-sensitive PC (synchronous and metachronous), the overall survival benefit associated with good tolerability makes the combination of ADT and novel hormonal agents (NHA) a standard. For patients with high-volume/high-risk de novo metastatic disease, treatment with docetaxel in addition to ADT + NHA can be discussed for eligible patients. In patients with castration-resistant prostate cancer (CRPC), the contribution of new therapies that have become available in recent years, as well as the advent of precision medicine, help to improve the control of tumour progression and survival, and highlight the value of testing for alterations in DNA repair genes within the tumour tissue or constitutionally. CONCLUSION: This update of the French recommendations should help to improve the management of patients with prostate cancer.

[Bladder-sparing trimodal therapy for muscle invasive bladder cancer]. / Stratégie de préservation vésicale basée sur le traitement trimodal : quelle place dans la prise en charge du carcinome infiltrant de la vessie ?

Organ-sparing strategies in the management of local or locally advanced cancers meet a dual objective: tumor control and preservation of the function of the involved organ. Given the morbidity and mortality of cystectomy and its impact on quality of life and bladder function, bladder-sparing strategies have emerged for the management of urothelial muscle invasive bladder cancer, mostly through trimodal treatment, which consists in maximal trans-urethral resection of bladder tumor, followed by chemo-radiotherapy. This review presents the modalities of trimodal treatment, before exposing the advantages and limitations of this strategy compared to cystectomy among operable patients. Despite the absence of comparative data from randomized trials, the two approaches seem to provide similar oncological results among appropriately selected patients. In modern series, the rate of salvage cystectomy is approximately 15% at 5 years; this delayed cystectomy does not seem to be associated with greater morbidity and mortality as compared to upfront cystectomy. Emphasis is placed in the review on quality of life data of these two approaches. In order to optimize the selection of patients eligible to trimodal therapy, the classical predictive factors of response to radio(chemo)therapy are critically analyzed, with the perspective of innovative molecular biomarkers. Finally, a close multidisciplinary collaboration is needed for the choice and the execution of the therapeutic strategy, and the patient should be fully involved in the decision-making process.

[Recent advances in the management of localized high-risk prostate cancer: An update by the Prostate Cancer Committee of the French Association of Urology]. / Avancées récentes dans la prise en charge du cancer de la prostate localisé à haut risque : mise au point par le Comité Prostate de l'Association française d'urologie.

INTRODUCTION: The risk of recurrence is increased in localized high-risk prostate cancer (PCa). The implementation of an appropriate diagnostic and therapeutic strategy is essential. The objective of this update by the Prostate Committee of the French Association of Urology was to report the most recent data in the management of localized high-risk PCa. MATERIAL AND METHODS: This update is based on the data available in the literature on localized high-risk PCa. A PubMed search and narrative review of the recent data were performed in March 2022. RESULTS: Compared with conventional imaging, PET-PSMA is more effective for the diagnosis of lymph nodes and distant metastases. Two recent randomized clinical trials have failed to prove the oncologic benefit of extended pelvic lymph node dissection during radical prostatectomy (RP). Postoperatively, early salvage radiotherapy is the standard of care, with adjuvant radiotherapy becoming an option in case of unfavorable pathological criteria (ISUP 4-5, pT3±positive margins) in young patients. Although promising, perioperative systemic therapies (chemotherapy, second-generation hormonotherapy) cannot be recommended at this time when the patient is treated by RP. Regarding radiotherapy, prophylactic lymph node irradiation during prostatic irradiation was associated with improved biochemical and metastasis-free survival in a recent randomized trial but it is still controversial. Since the publication of the results of the STAMPEDE trial, the addition of abiraterone acetate to radiation-hormone therapy should be considered the new standard of care for patients with localized (very) high-risk PCa, according to the inclusion criteria of the study. CONCLUSION: The most recent data of the literature regarding the management of high-risk localized PCa redefine the diagnostic performance of molecular imaging, the timing of postoperative radiotherapy, the oncologic benefit of pelvic lymph node treatment, and the intensification of systemic therapies.

[DNA repair gene alterations testing in prostate cancer : A practical update by the prostate cancer committee of the french association of urology]. / Recherche d'altérations des gènes de réparation de l'ADN dans le cancer de la prostate : mise au point pratique du Comité de cancérologie de l'association française d'urologie.

INTRODUCTION: Current therapeutic developments in prostate cancer (PCa) tend to increasingly personalize the treatment strategy, in particular as a function of tumor genomics. Recently, poly ADP-ribose polymerase (PARPi) inhibitors have shown their efficacy at the stage of castration resistance, in case of alteration of DNA repair genes in tumor tissue. MATERIAL AND METHODS: A narrative review was carried out on recent data in the literature since 2000. A consensus among the members of the Committee was obtained in order to synthesize the current data, with a particular focus on the practical considerations regarding indications and developments of molecular testing circuits concerning DNA repair genes, for theranostics purpose. RESULTS: The establishment of an efficient molecular testing network is based on the multidisciplinary organization of the various actors and the coordination of all material resources. Its goal is the routine search for somatic mutations (in tumor tissue) of BRCA1/2 genes in patients who may benefit from PARPi. The current indications are for BRCA1 or 2 mutated castration-resistant metastatic PCa after next-generation hormone therapy failure. The demand for molecular testing must be decided in the tumor board, giving priority to archived tissue less than 10 years old. In case of unsuccess, biopsies of the primary or metastases, or even analysis of circulating tumor DNA, may be necessary. Any demand for a genetic test on tumor tissue must be accompanied by detailed information for the patient on the possible familial consequences, in case of associated germline mutation. CONCLUSION: This article aims to guide the practical implementation of molecular testing circuits for DNA repair genes alterations, in order to guide the therapeutic management of patients with advanced PCa.

Management of patients with a persistently elevated PSA after radical prostatectomy: a narrative review.

INTRODUCTION: The management of the postoperative biological relapse of prostate cancer is most often based on salvage radiotherapy (SRT) with or without the addition of a variable duration of hormone therapy (HT). The indications for SRT +/- HT are established in the setting of a rising PSA level after a period where an undetectable PSA was achieved. However, in case of detectable PSA immediately after radical prostatectomy, the treatment options and prognosis are still unclear. MATERIALS AND METHODS: We conducted a narrative review based on an analysis of the literature focusing on articles targeting the population of patients with postoperative persistently detectable PSA level. Case reports, original articles, clinical trials, and published reviews were studied for this purpose. CONCLUSION: This article will describe current management of patients with detectable PSA immediately after radical prostatectomy, notably the contribution of modern imaging and new treatment options involving the combination of RT and HT.

External radiotherapy for prostatic cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on external radiotherapy of prostate cancer. External radiotherapy is intended for all localized prostate cancers, and more recently for oligometastatic prostate cancers. The irradiation techniques are detailed. Intensity-modulated radiotherapy combined with prostate image-guided radiotherapy is the recommended technique. A total dose of 74 to 80Gy is recommended in case of standard fractionation (2Gy per fraction). Moderate hypofractionation (total dose of 60Gy at a rate of 3Gy per fraction over 4 weeks) in the prostate has become a standard of therapy. Simultaneous integrated boost techniques can be used to treat lymph node areas. Extreme hypofractionation (35 to 40Gy in five fractions) using stereotactic body radiotherapy can be considered a therapeutic option to treat exclusively the prostate. The postoperative irradiation technique, indicated mainly in case of biological recurrence and lymph node involvement, is detailed.

Conformal radiotherapy in management of soft tissue sarcoma in adults.

We present the update of the recommendations of the French society of radiation oncology on soft tissue sarcomas. Currently, the initial management of sarcomas is very important as it may impact on patients' quality of life, especially in limb soft tissue sarcomas, and on overall survival in trunk sarcomas. Radiotherapy has to be discussed within a multidisciplinary board meeting with results of biopsy, eventually reexamined by a dedicated sarcoma pathologist. The role of radiotherapy varies according to localization of soft tissue sarcoma. It is part of the standard treatment in grade 2 and 3 sarcomas of the extremities and superficial trunk>5cm. In case of R1 or R2 resection, reexcision should be discussed. In such cases, it may be delivered preoperatively (50Gy/25 fractions of 2Gy) or postoperatively. In retroperitoneal sarcomas, preoperative conformal radiotherapy with or without modulated intensity cannot be proposed systematically in daily practice. Concomitant chemoradiotherapy cannot be considered a standard treatment. Intensity-modulated radiotherapy has become widely available. Other soft tissue sarcoma sites such as trunk, head and neck and gynaecological soft tissue sarcomas will be addressed, as well as other techniques that may be used such as brachytherapy and proton therapy.

Narrative review of PET/CT performances at biochemical recurrence in prostate cancer after radical prostatectomy and impact on patient disease management: Revue narrative à propos des performances de la TEP/TDM en cas de récidive biochimique après prostatectomie radicale dans le cancer de la prostate et impact sur la prise en charge des patients.

Patients treated by radical prostatectomy (RP) for localized prostate cancer (PCa) may experience biochemical recurrence (BCR) in approximately 30% of cases. Recently, advances in imaging modalities and in particular Positron-Emission Tomography with computed tomography (PET/CT) imaging allow for better detection and characterization of lesions outside the prostatic bed at recurrence. Thus, treatment at BCR can be significantly improved by a tailored strategy based on new generation imaging. A more precise and accurate staging of the disease at recurrence paves the way to more appropriate treatment, potentially translating into better survival outcomes of these patients. This review therefore highlights the interest of PET/CT at the time of BCR, its superiority over standard imaging in terms of staging, and its impact on guiding the different therapeutic possibilities depending on the site, number, and volumes of recurrence. Indeed, we will discuss below about different strategies and their indications: salvage radiotherapy of the prostate bed, systemic therapies, stereotactic body radiotherapy and others therapeutical strategies. The various innovative approaches based on PET/CT implementation are partly underway within protocol trials to prove their benefits on clinically meaningful endpoints. © 2022 Elsevier Masson SAS. All rights reserved.

How PET-CT is Changing the Management of Non-metastatic Castration-resistant Prostate Cancer?: Comment la TEP-TDM Peut Modifier la Prise en Charge du Cancer de la Prostate Non Métastatique Résistant à la Castration ?

INTRODUCTION: The aim of this narrative review conducted by the Prostate Cancer Committee of the French Association of Urology (CC-AFU) was to provide an update on the current evidence for the impact of PET/CT in the management of men with non-metastatic castration-resistant prostate cancer (nmCRPC). MATERIAL AND METHODS: This review is based on data available in the literature on PET/CT imaging for staging nmCRPC patients. A PubMed search and narrative review of the data were performed in March 2022. Only articles in French or English were considered. RESULTS: Current guidelines recommend bone scan and CT scan as standard imaging modalities for staging and follow-up of patients with nmCRPC. Nearly one-third of asymptomatic patients with presumed nmCRPC ultimately have metastatic disease on conventional imaging. Increasing reports have shown that conventional imaging has limited accuracy in detecting metastatic disease in nmCRPC patients, leading to the development of next-generation imaging techniques. In a retrospective study, 18F-choline PET/CT detected distant metastases in 27/58 high-risk nmCRPC patients with prior negative conventional imaging. The implementation of radiolabeled ligands of the prostate-specific membrane antigen (PSMA) PET/CT in staging strategy has resulted in metastasis detection in 45% to 98% of patients with presumptive nmCRPC on conventional imaging. Such an early diagnosis of metastatic CRPC may allow patients to be referred for metastasis-directed therapies (i.e. stereotactic body radiotherapy), aimed at prolonging the efficacy of systemic therapies and improving clinical outcomes. However, current data are not strong enough to recommend this strategy, which must be properly evaluated in clinical trials. Indeed, the use of molecular imaging may lead to inappropriate undertreatment if the second-generation androgen receptor inhibitors (darolutamide, enzalutamide, apalutamide), which prolong life, are not used in the subgroup of patients with high PSA velocity (PSA doubling time <10 months). CONCLUSION: Implementation of PSMA-PET/CT in the staging strategy would result in a migration of disease stage to extra-pelvic, M1 disease in at least half of presumed nmCRPC patients. The unprecedented accuracy of PSMA-PET/CT may pave the way for a more personalized treatment strategy. However, no data yet support this strategy for all nmCRPC patients as no oncologic benefit of early detection of M1 disease or MDT has been demonstrated. © 2022 Elsevier Masson SAS. All rights reserved.

[Salvage radiotherapy after prostatectomy - what do do in case of elevated post operative PSA or macroscopic relapse?] / Radiothérapie de rattrapage après prostatectomie radicale : que faire en cas de concentration de PSA postopératoire élevée persistante ou de récidive locale macroscopique ?

The management of the postoperative biological relapse of prostate cancer is most often based on salvage radiotherapy (RT) and a variable duration of hormone therapy (HT) in addition. The indications for RT±HT become more consensual for the adjuvant postoperative situation or in the event of a rising PSA level after a period where an undetectable PSA level was achieved. On the other hand, in the event of detectable PSA immediately postoperatively or in the event of a biological recurrence with macroscopic relapse in the prostate bed seen on conventional imaging assessment, the treatment options are still being evaluated. This article will describe these 2 situations and their current management but also will come through assessments with the contribution of modern imaging and new treatment options in terms of RT dose and RT±HT combination.

A practical approach to bladder preservation with hypofractionated radiotherapy for localised muscle-invasive bladder cancer.

Bladder preservation with trimodality treatment (TMT) is an alternative strategy to radical cystectomy (RC) for the management of localised muscle invasive bladder cancer (MIBC). TMT comprises of transurethral resection of the bladder tumour (TURBT) followed by radiotherapy with concurrent radiosensitisation. TMT studies have shown neo-adjuvant chemotherapy with cisplatin-based regimens is often given to further improve survival outcomes. A hypofractionated radiotherapy regimen is preferable due to its non-inferiority in local control and late toxicities. Radiosensitisation can comprise concurrent chemotherapy (with gemcitabine, cisplatin or combination fluorouracil and mitomycin), CON (carbogen and nicotinomide) or hyperthermic treatment. Radiotherapy techniques are continuously improving and becoming more personalised. As the bladder is a mobile structure subject to volumetric changes from filling, an adaptive approach can optimise bladder coverage and reduce dose to normal tissue. Adaptive radiotherapy (ART) is an evolving field that aims to overcome this. Improved knowledge of tumour biology and advances in imaging techniques aims to further optimise and personalise treatment.