What's new about the tumor microenvironment of urothelial carcinoma?

Urothelial carcinoma is a significant global health concern that accounts for a substantial part of cancer diagnoses and deaths worldwide. The tumor microenvironment is a complex ecosystem composed of stromal cells, soluble factors, and altered extracellular matrix, that mutually interact in a highly immunomodulated environment, with a prominent role in tumor development, progression, and treatment resistance. This article reviews the current state of knowledge of the different cell populations that compose the tumor microenvironment of urothelial carcinoma, its main functions, and distinct interactions with other cellular and non-cellular components, molecular alterations and aberrant signaling pathways already identified. It also focuses on the clinical implications of these findings, and its potential to translate into improved quality of life and overall survival. Determining new targets or defining prognostic signatures for urothelial carcinoma is an ongoing challenge that could be accelerated through a deeper understanding of the tumor microenvironment.

Chemotherapy: A partnership with immunotherapy in non-small cell lung cancer.

Chemotherapy (CT) and immunotherapy (IO) act synergically in the treatment of non-small cell lung cancer (NSCLC). However, the molecular basis of such interaction is poorly understood. The aim of this review was to explore the mechanisms of CT to potentiate the immune system and, consequently, the action of IO. The most up-to-date knowledge concerning the interaction of CT and IO in NSCLC was reviewed and a bibliographic search was made in PubMed/Medline database, using the mentioned keywords, with preference given to recently published articles in English. In addition to the direct cytotoxic effect, CT affects the immune system leading indirectly to cell death. The immune response triggered by PD-1 inhibition is enhanced by the cytotoxic immunogenic effects of CT. This potentiation phenomenon occurs due to an increase in effector cells relatively to regulatory cells, inhibition of myeloid derived suppressor cells, increased potential for cross-presentation by dendritic cells after the death of tumor cells or blocking the STAT6 pathway to increase dendritic cell activity. In conclusion, the effects of CT on the immune system work in synergy with the actions of IO, transforming "cold" tumors into "hot" tumors, which are more visible to the immune system.

Immunotherapy in Elderly Patients-Single-Center Experience.

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.

Specialist management of testicular cancer: Report of the last 10 years at a Portuguese tertiary referral academic centre.

OBJECTIVES: To describe our experience on testicular cancer (TC) management, underlining the clinical/pathological scope, administered treatments, outcomes, and challenges. TC incidence is rising globally. The predominant histology is germ cell tumour (GCT). In most patients, orchiectomy is curative. Still, a significant proportion of patients will need further tailored treatment. Specialist Reference Centres have proven themselves successful in this setting. Published data regarding TC in Northern Portugal is lacking. METHODS: Retrospective review of consecutive TC patients at a specialist tertiary referral academic centre between January 2010 and December 2020. Statistical analysis was performed using the STATA® version 13.1 software. Multivariate logistic and survival analyses were performed. RESULTS: 125 patients met the inclusion criteria. The median age is 35 (28-40) years; 19% of patients had risk factors for TC - infertility being the most common (11%); 50% of patients wanted sperm cryopreservation prior to treatment; 68% of patients had stage I GCT, 16% stage II, and 17% stage III. Compared to seminoma, non-seminomatous GCT were associated with younger age (p < .001) and higher stages at diagnosis (p = .02); 24% of stage IA/B GCT underwent adjuvant chemotherapy; 47% of patients with metastatic GCT at presentation had refractory disease, requiring tailored treatment. The median follow-up time is 33 (13-65) months. There was no late relapse. The 5-year OS rate is 98.0%. The 5-year survival of metastatic disease is 95.8%. CONCLUSIONS: Despite contemporary excellent cure rates, the challenges of testicular cancer management still endure, especially in advanced stages. Therefore, public awareness is recommended, in order to avoid late presentations - special attention should be given to those who have known risk factors. The existence of Reference Centres is of paramount importance in order to achieve the best outcomes possible.