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Abstract The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient’s plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.

Biochemical recurrence is an evolving space in prostate cancer, with increasing multidisciplinary involvement. Androgen deprivation therapy has shown proof of its value in complementing salvage radiotherapy in high-risk biochemical relapsing patients; ongoing trials aim to further refine this treatment combination. As systemic treatments, and notably next-generation androgen receptor targeted agents, have moved towards early hormone-sensitive and non-metastatic stages, the prostate specific antigen (PSA)-relapse disease stage will be undoubtedly challenged by future evidence from such ongoing clinical trials. With the use of modern imaging and newer molecular technologies, including integration of tumoral genomic profiling and liquid biopsies in risk stratification, a path towards a precision oncology-focused approach will become a reality to guide in the future decisions for patients with a diagnosis of biochemical recurrence.

Abstract Purpose A substantial proportion of cancer survivors experience fatigue after diagnosis. Physical activity (PA) can impact fatigue after cancer. In this study, we evaluated the prevalence and association of fatigue and the practice of PA in a population with early cancer. Methods Using the national population‐based French cross‐sectional study Vie après le cancer 2, we included 1984 patients with early breast (61.1%), prostate (21.5%), and colorectal (17.4%) cancer. Severe fatigue at 2 years postdiagnosis was defined by a score ≥40 in the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ C30) fatigue subscale. PA was defined as (a) self‐reported PA before diagnosis (active/inactive) and (b) change in PA since diagnosis (increased/maintained exposure vs decreased exposure/remaining inactive). Multivariate regression examined associations of severe fatigue with PA, adjusting for baseline clinical and treatment variables. Results Median age was 52 years. 51.5% of patients experienced severe fatigue 2 years post‐diagnosis. 87.7% reported to be physically active before cancer diagnosis; 53.3% of patients either decreased PA or remained inactive at 2 years postdiagnosis. At 2 years postdiagnosis, severe fatigue was associated with a change in PA since diagnosis: patients with decreasing PA/remaining inactive from pre‐ to postdiagnosis had a higher risk of severe fatigue vs those with increasing/maintaining PA (adjusted odds ratio [95% confidence interval] 2.32 [1.85‐2.90]). Conclusion Fatigue continues to be a substantial problem for cancer survivors 2 years after cancer diagnosis and is associated with PA decreasing/remaining inactive since diagnosis. Interventions to maintain or increase PA for cancer survivors should be tested to mitigate long‐term fatigue after cancer.

Until recently, continuing androgen deprivation therapy (ADT) and closely monitoring patients until evolution towards metastatic castration-resistant prostate cancer (CRPC) were recommended in men with non-metastatic CRPC (nmCRPC). Because delaying the development of metastases and symptoms in these patients is a major issue, several trials have investigated next-generation androgen receptor (AR) axis inhibitors such as apalutamide, darolutamide, and enzalutamide in this setting. This review summarizes the recent advances in the management of nmCRPC, highlighting the favourable impact of next-generation AR inhibitors on metastases-free survival, overall survival and other clinically meaningful endpoints.

Abstract Background Prostate cancer is one of the most common cancers in men and the fourth leading cause of cancer mortality worldwide. Although major progress has been achieved in the last years for patients with metastatic castrate-resistant prostate cancer (mCRPC), thanks to next-generation androgen receptor axis targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been widely approved and used for the treatment of prostate cancer. Two large studies with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody reported improved progression-free survival, but not statistically improved overall survival at the primary analysis (CA184 043 and CA184 095). Case presentation Here, we report on two patients who received ipilimumab in these trials and are still in long-term complete remission with a follow-up of 64 and 52 months respectively after the initiation of ipilimumab. Immunohistochemical staining for hMLH1, hMSH2, hMSH6 and PMS2 was performed on archival prostate biopsy samples from one of the two patients; they exhibited normal protein expression. Interestingly for this patient, a high CD3+ and CD8+ T cell infiltration was observed on archival prostate biopsies as well as Treg FoxP3+ T cells. Conclusion Ipilimumab produces clinical activity in patients with CRPC, including very long responders with no detectable residual disease.