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Simple Summary: The rising global aging population poses a notable challenge in cancer management due to increased cancer incidence with age. The use of immune checkpoint inhibitors (ICI) in the treatment of different solid tumors presented as a less toxic alternative compared to chemotherapy treatment for elderly patients. However, the age-related remodeling process of the immune system, termed immunosenescence, is hypothesized to impact the efficacy of ICI in the geriatric oncology population. This study provides additional evidence to support the safety and efficacy of ICI in the treatment of elderly cancer patients by using a retrospective, single-center cohort design to analyze survival outcomes and the response rate of 220 patients. Overall, the study challenges the notion of age as a sole determinant for treatment decisions, highlighting the importance of comprehensive geriatric assessments for personalized cancer care in the elderly and the need for further research in this area. Cancer management faces a substantial challenge posed by the aging demographic. Aging is marked by accumulated DNA damage, and this phenomenon is implicated in the process of tumorigenesis. The concept of immunosenescence, postulated to manifest in elderly individuals, is defined by an age-related decline in T cells and a simultaneous elevation in proinflammatory status, leading to a diminished efficacy in response to immunotherapy. Notably, despite the rising prevalence of cancer in the elderly population, their underrepresentation in clinical trials persists. This underscores the unmet need to evaluate the safety and efficacy of cancer treatment in the elderly. This retrospective, single-center cohort study aimed to assess and evaluate the effectiveness and safety of immunotherapy in patients compared to younger individuals with metastatic solid tumors receiving ICI. A total of 220 patients were included, mostly males, with a median age of 64. The proportion of patients ≥ 65 years old was 56.5%. The use of ICI showed no significant differences concerning overall survival (OS) and progression-free survival (PFS) among age groups across different cancer types (melanoma, non-small-cell lung cancer (NSCLC), renal, and bladder cancer; p = 0.388). Concerning the response to treatment in renal cancer patients, a significant difference was observed (p = 0.041), suggesting a potential negative impact of age on the treatment response. In patients that presented immune-related adverse events (irAEs), oral corticosteroid therapy was marginally associated (p = 0.059) with the elderly population. When evaluating the NSCLC population alone (n = 131, 59.5%), our study revealed a strong association between the development of irAEs, patients' PFS and OS, and the duration of ICI treatment, but not directly correlated with age. The NSCLC elderly population presented a marginally greater number of irAEs, although without statistical significance (p = 0.86). ICI maintained efficacy and safety in elderly patients, challenging the notion that age alone should determine treatment decisions. The findings emphasize the necessity of a comprehensive geriatric assessment rather than relying solely on chronological age for personalized cancer treatment in the elderly population. Further prospective studies are needed to better understand immune responses in older adults and derive predictive biomarkers for cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The majority of high grade serous ovarian carcinoma (HGSOC) patients present with advanced disease, which will relapse and require additional treatment. Although the presence of ascites and/or pleural effusion in relapsed HGSOC is not rare, there is a lack of data in this setting. This population of patients typically presents a very poor prognosis and often there is no response to the treatment. One could ask if giving the "right therapy to the right patients" would change the course of the disease. The aim of this retrospective, multi-centric and real-life study was to compare the overall survival (OS) of two groups of advanced HGSOC patients, who present with ascites or pleural effusion: responders, i.e., patients that had an imagological response to treatment (complete/partial response/stable disease, RECIST criteria) versus non-responders (no response/progression upon treatment), and to evaluate the predictive value of the standard clinical variables. We concluded that patients who have a tumoral response to first and second line of treatment have a ~3 times longer Progression-free Survival (PFS) or OS. The response to the treatment was irrespective of patient and tumor characteristics, which highlights the need for a sensitivity test to tailor treatments and improve efficacy rates in a personalized manner. (1) Background: Relapsed HGSOC with ascites and/or pleural effusion is a poor-prognostic population and poorly represented in clinical studies. We questioned if these patients are worth treating. In other words, if these patients received the most effective treatment, would it change the course of this disease? To our knowledge this is the first real-life study to evaluate this question in this low-survival population. (2) Methods: To tackle this question we performed a retrospective, multi-centric, real-life study, that reviewed relapsed HGSOC patients with ascites and/or pleural effusion. Our rationale was to compare the OS of two groups of patients: responders, i.e., patients who had an imagological response to treatment (complete/partial response/stable disease, RECIST criteria) versus non-responders (no response/progression upon treatment). We evaluated the predictive value of clinical variables that are available in a real-life setting (e.g., staging, chemotherapy, surgery, platinum-sensitivity). Multivariate logistic regression and survival analysis was conducted. A two-step cluster analysis SPSS tool was used for subgroup analysis. Platinum sensitivity/resistance was also analyzed, as well as multivariate and cluster analysis. (3) Results: We included 57 patients, 41.4% first line responders and 59.6% non-responders. The median OS of responders was 23 months versus 8 months in non-responders (p < 0.001). This difference was verified in platinum-sensitive (mOS 28 months vs. 8 months, p < 0.001) and platinum-resistant populations (mOS 16 months vs. 7 months, p < 0.001). Thirty-one patients reached the second line, of which only 10.3% responded to treatment. Three patients out of thirty-one who did not respond in the first line of relapse, responded in the second line. In the second line, the mOS for the responders' group vs. non-responders was 31 months versus 13 months (p = 0.02). The two step cluster analysis tool found two different subgroups with different prognoses based on overall response rate, according to consolidation chemotherapy, neoadjuvant chemotherapy, FIGO staging and surgical treatment. Cluster analysis showed that even patients with standard clinical and treatment variables associated with poor prognosis might achieve treatment response (the opposite being also true). (4) Conclusions: Our data clearly show that relapsed HGSOC patients benefit from treatment. If given an effective treatment upfront, this can lead to a ~3 times increase in mOS for these patients. Moreover, this was irrespective of patient disease and treatment characteristics. Our results highlight the urgent need for a sensitivity test to tailor treatments and improve efficacy rates in a personalized manner. [ABSTRACT FROM AUTHOR]