Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial.

BACKGROUND: Patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA alterations have poor outcomes. MAGNITUDE found patients with homologous recombination repair gene alterations (HRR+), particularly BRCA1/2, benefit from first-line therapy with niraparib plus abiraterone acetate and prednisone (AAP). Here we report longer follow-up from the second prespecified interim analysis (IA2). PATIENTS AND METHODS: Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1 : 1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints [time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival (OS)] were assessed. RESULTS: Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n = 113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival {rPFS; blinded independent central review; median rPFS 19.5 versus 10.9 months; hazard ratio (HR) = 0.55 [95% confidence interval (CI) 0.39-0.78]; nominal P = 0.0007} consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population [HR = 0.76 (95% CI 0.60-0.97); nominal P = 0.0280; median follow-up 26.8 months]. Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR of 0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies, demonstrated an HR of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed. CONCLUSIONS: MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients.

[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.

Impact of acetaminophen on the efficacy of immunotherapy in cancer patients.

BACKGROUND: Acetaminophen (APAP) use has been associated with blunted vaccine immune responses. This study aimed to assess APAP impact on immunotherapy efficacy in patients with cancer. PATIENTS AND METHODS: Exposure to APAP was assessed by plasma analysis and was correlated with clinical outcome in three independent cohorts of patients with advanced cancer who were treated with immune checkpoint blockers (ICBs). The immunomodulatory effects of APAP were evaluated on a preclinical tumor model and on human peripheral blood mononuclear cells (PBMCs) from healthy donors. RESULTS: Detectable plasma APAP levels at treatment onset were associated with a significantly worse clinical outcome in ICB-treated cancer patients, independently of other prognostic factors. APAP significantly reduced ICB efficacy in the preclinical MC38 model, as well as the production of PD-1 blockade-related interferon-γ secretion by human PBMCs. Moreover, reduction of ICB efficacy in vivo was associated with significantly increased tumor infiltration by regulatory T cells (Tregs). Administration of APAP over 24 h induced a significant expansion of peripheral Tregs in healthy individuals. In addition, interleukin-10, a crucial mediator of Treg-induced immune suppression, was significantly up-regulated upon treatment with ICB in cancer patients taking APAP. CONCLUSIONS: This study provides strong preclinical and clinical evidence of the role of APAP as a potential suppressor of antitumor immunity. Hence, APAP should be used with caution in patients treated with ICB.

Circulating L-arginine predicts the survival of cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: The discovery of immune checkpoint inhibitors (ICIs) has revolutionized the systemic approach to cancer treatment. Most patients receiving ICIs, however, do not derive benefits. Therefore, it is crucial to identify reliable predictive biomarkers of response to ICIs. One important pathway in regulating immune cell reactivity is L-arginine (ARG) metabolism, essential to T-cell activation. We therefore aimed to evaluate the association between baseline plasma ARG levels and the clinical benefit of ICIs. PATIENTS AND METHODS: The correlation between ARG levels and clinical ICI activity was assessed by analyzing plasma samples obtained before treatment onset in two independent cohorts of patients with advanced cancer included in two institutional molecular profiling programs (BIP, NCT02534649, n = 77; PREMIS, NCT03984318, n = 296) and from patients in a phase 1 first-in-human study of budigalimab monotherapy (NCT03000257). Additionally, the correlation between ARG levels and ICI efficacy in preclinical settings was evaluated using a syngeneic mouse model of colorectal cancer responsive to ICIs. Using matched peripheral blood mononuclear cell (PBMC) plasma samples, we analyzed the correlation between ARG levels and PBMC features through multiplexed flow cytometry analysis. RESULTS: In both discovery and validation cohorts, low ARG levels at baseline (<42 µM) were significantly and independently associated with a worse clinical benefit rate, progression-free survival, and overall survival. Moreover, at the preclinical level, the tumor rejection rate was significantly higher in mice with high baseline ARG levels than in those with low ARG levels (85.7% versus 23.8%; P = 0.004). Finally, PBMC immunophenotyping showed that low ARG levels were significantly associated with increased programmed death-ligand 1 expression in several immune cell subsets from the myeloid lineage. CONCLUSIONS: We demonstrate that baseline ARG levels predict ICI response. Plasma ARG quantification may therefore represent an attractive biomarker to tailor novel therapeutic regimens targeting the ARG pathway in combination with ICIs.

[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.

[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.

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.

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.

A phase II trial of high-dose chemotherapy (HDCT) supported by hematopoietic stem-cell transplantation (HSCT) in germ-cell tumors (GCTs) patients failing cisplatin-based chemotherapy: the Multicentric TAXIF II study.

BACKGROUND: High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT. PATIENTS AND METHODS: This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients received two cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen. The main objective was to determine the complete response rate. RESULTS: Forty-five patients were included between September 2004 and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4-51), the final overall response rate was 48.8% (including a complete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval (CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95% CI 44-81). CONCLUSION: The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens. TRIAL REGISTRATION NUMBER: NCT00231582.

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.

A phase II study (AARDVARC) of AZD4635 in combination with durvalumab and cabazitaxel in patients with progressive, metastatic, castration-resistant prostate cancer.

BACKGROUND: This phase II nonrandomized study evaluated the efficacy and safety of AZD4635 in combination with durvalumab (Arm A) or durvalumab plus cabazitaxel (Arm B) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and ≥1 novel hormonal agent. PATIENTS AND METHODS: The primary endpoint was radiographic progression-free survival (rPFS) per RECIST v1.1 (soft tissue) or the Prostate Cancer Clinical Trials Working Group 3 (bone). Secondary endpoints included safety, tolerability, overall survival, confirmed prostate-specific antigen (PSA50) response, pharmacokinetics, and objective response rate. Enrollment in Arm A was stopped following a sponsor decision unrelated to safety. The study was stopped based on the planned futility analysis due to low PSA50 response in Arm B. RESULTS: In the final analysis (1 November 2021), 30 patients were treated (Arm A, n = 2; Arm B, n = 28). The median rPFS in Arm B was 5.8 months (95% confidence interval 4.2-not calculable). Median rPFS was 5.8 months versus 4.2 months for patients with high versus low blood-based adenosine signature. The most common treatment-related adverse events in Arm B were nausea (50.0%), diarrhea (46.4%), anemia and neutropenia (both 35.7%), asthenia (32.1%), and vomiting (28.6%). Overall, AZD4635 in combination with durvalumab or AZD4635 in combination with cabazitaxel and durvalumab showed limited efficacy in patients with mCRPC. CONCLUSIONS: Although the safety profile of both combinations was consistent with known safety data of the individual agents, the results of this trial do not support further development of the combinations.

Gastrointestinal metastases in renal cell carcinoma: A retrospective multicenter GETUG (Groupe d'Étude des Tumeurs Uro-Génitales) study.

BACKGROUND: Among patients with renal cell carcinoma (RCC), bone and visceral metastases have a poor prognosis, while endocrine gland metastases have a more favorable prognosis. Gastrointestinal metastases (GIMs) are rare, and their prognosis is still poorly understood. OBJECTIVES: To report clinical presentations, patient characteristics, therapeutic strategies, and prognosis of GIMs from RCC. METHODS: We retrospectively collected data from RCC patients presenting GIMs, in 10 French GETUG centers, between 2000 and 2021. RESULTS: We identified 74 patients with 87 GIMs, mostly gastric or duodenal. The median age at GIM diagnosis was 69 years and 76% of patients already had other metastases. GIMs occurred after a median duration of 5.4 years (IC95%=[4.2-7.1]) and 1.9 years (IC95%=[1.2-3.8]) from RCC diagnosis and first metastasis, respectively. GIMs were symptomatic in 52 patients (70%), with anemia in 41 patients (55%) and/or gastrointestinal bleeding in 31 patients (42%). Only 22 asymptomatic patients (30%) were fortuitously diagnosed. GIM management consisted of systemic treatment only in 29 GIMs (33%), local treatment only in 23 GIMs (26%), and both local and systemic treatment in 18 GIMs (21%). For 17 GIMs (20%), there was no therapeutic modification. After diagnosis of GIM, median overall survival was 19 months. CONCLUSION: We report the largest retrospective cohort of GIMs in RCC patients. They should be suspected in case of anemia or gastrointestinal bleeding in any patient with a history of RCC. Their management varies widely depending on their location in the digestive tract and whether or not they are symptomatic.

Combination of gemcitabine and doxorubicin in rapidly progressive metastatic renal cell carcinoma and/or sarcomatoid renal cell carcinoma.

BACKGROUND/AIMS: Metastatic renal cell carcinoma (mRCC) can be rapidly progressive when tumors exhibit sarcomatoid or Fuhrman grade 4 features. Efficacy of gemcitabine (Gem) with doxorubicin (Dox) in sarcomatoid or rapidly progressive mRCC has been reported. We retrospectively evaluated Gem + Dox in a consecutive cohort of this particular patient population. PATIENTS AND METHODS: Patients had an Eastern Cooperative Oncology Group performance status of 2 or more and rapidly progressive mRCC or mRCC with sarcomatoid features. Gem (1,500 mg/m(2)) and Dox (50 mg/m(2)) were given every 2 weeks with granulocyte colony-stimulating factor. RESULTS: Twenty-nine patients were treated. Sarcomatoid features were predominant in 6 patients, while 14 tumors were Fuhrman grade 4. All patients had progressive mRCC within 4 months. No grade 4 toxicity or drug-related death was reported. One partial response (7 months), 1 mixed response, and 14 stable diseases (≥4 months for 9 patients) were observed and no response was seen in sarcomatoid tumors. The median disease-free survival was 3.7 months (≥6 months for 8 patients) and the median overall survival was 4.8 months (>12 months for 5 patients). CONCLUSION: This study showed a lower response rate than previously reported. Nevertheless, some patients had prolonged survival outcomes. This combination could be an option in sarcomatoid histology (NCCN guidelines) or rapidly progressive disease, but this population represents an unmet medical need.

[Plan of the day adaptive radiotherapy for bladder cancer: Dosimetric and clinical results]. / Résultats dosimétriques et cliniques d'une stratégie de radiothérapie adaptativede type "bibliothèque de plans" des cancers de la vessie localisés.

PURPOSE: To account of individual intra-pelvic anatomical variations in muscle invasive bladder cancer (MIBC) irradiation, adaptive radiotherapy (ART) using a personalized plan library may have dosimetric and clinical benefits. MATERIAL AND METHODS: The data from ten patients treated for localized MIBC according to the "plan of the day" (P0oD) individualized ART technique were collected and retrospectively analysed. Target volumes and organs at risk (OAR) were delineated at different bladder fill rates, resulting in two or three treatment plans. Daily Cone-Beam CT (CBCT) was used for the selection of PoD at each fraction. Retrospectively, we delineated rectal, intestinal and target volumes on each CBCT, to assess target volume coverage and dose sparing to healthy tissues. A comparison with the conventional radiotherapy technique was performed. The secondary objectives were toxicity and efficacy. RESULTS: The target coverage was respected with the adaptive treatment: 97.3% for the bladder Clinical Target Volume (CTV) (99.5; [60.1-100]) and 98% for the bladder+lymph nodes CTV (98.6; [85.4-100]). Concerning OAR, the volume of healthy tissue spared was 43.7% on average and the V45Gy for the small bowel was 43,4cc (35; [0-129]) (versus 57,6cc). The rectal D50 was on average 18,7Gy for the adaptive treatment (15.9; [2.4-44.1]) versus 17Gy with the conventional approach. With a median follow-up of 2.94 years (95% CI: [0.92-4.02]), we observed three grade 3 toxicities (30%). No grade 4 toxicity was observed. The 2-year overall survival and progression-free survival rates were 65.6% (95% CI: [26-87.6]) and 45.7% (95% CI: [14.3-73]), respectively. CONCLUSION: The ART technique using a PoD strategy showed a reduction of the irradiated healthy tissue volume while maintaining a similar bladder coverage, with an acceptable rate of toxicity.

[Hypofractionnated radiotherapy for elderly patients with prostate cancer]. / Radiothérapie du cancer de la prostate localisé chez le sujet âgé : l'hypofractionnement modéré est-il le traitement de référence ?

Radiation therapy technique and schedules could be adapted to patient's age because of a natural history of prostate cancer perceived as different, taking into account the comorbidities of patients but also a particular tolerance of elderly subjects. Thus, in localized prostate cancer, evaluation of associated diseases is essential before considering a treatment that will be of interest only if the life expectancy is greater than 10 years. When a curative approach is decided, radiotherapy holds a place of choice. Due to the recent results of randomized studies evaluating moderate hypofractionnated radiotherapy, showing a carcinological equivalence compared to a standard fractionation, this reduction in the duration of treatment appears particularly indicated in this elderly population. This approach permits to maintain the quality of life of patients, potentially with lower costs for society. The purpose of this article is to present the results of randomized trials of moderate hypofractionnation and discuss their application in the population of elderly patients with localized prostate cancer.