2024 ASCO genitourinary cancers symposium: a focus on renal cell carcinoma.

In this article, we report the breakthrough acquisitions for renal cell carcinoma (RCC) management presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. The results from Keynote 564 showed an impressive overall survival (OS) advantage for pembrolizumab, in patients at higher risk of relapse after surgery and confirmed the benefit in terms of disease-free survival (DFS). Until now, pembrolizumab is the only immune checkpoint inhibitor (ICI) to prove a survival advantage. On the contrary, the results from CheckMate 914 trial showed the lack of benefit of adjuvant nivolumab. In the metastatic setting, the longer-term follow-up data of the CheckMate 9ER and CheckMate 214 trials reassessed the undoubtable role of ICI-based combination in first-line treatment, with a clear survival advantage in the subgroup of patients at intermediate/poor IMDC prognosis. No OS advantage was seen in favorable IMDC risk group patients. This 2024 ASCO Genitourinary Cancer Symposium laid the foundations for further knowledge development necessary for an increasingly personalized therapy for RCC patients.

Focus on RAS Codon 61 Mutations in Metastatic Colorectal Cancer: A Retrospective Analysis.

RAS mutations involving codon 61 are rare in metastatic colorectal cancer (mCRC), accounting for only 1-4%, but they have recently been identified with high frequency in the circulating tumor DNA (ctDNA) of patients with secondary resistance to anti-EGFRs. This retrospective monocentric study aimed to investigate the clinical phenotype and prognostic performance of codon 61 RAS-mutated mCRC. Fifty patients with codon 61 RAS-mutated mCRC treated at our institution between January 2013 and December 2021 were enrolled. Additional datasets of codon 61 RAS wild-type mCRCs (648 patients) were used as comparators. The endpoint for prognostic assessment was overall survival (OS). Metastatic involvement of the peritoneum or ovary was significantly more frequent in codon 61 RAS-mutated mCRC compared to codon 61 RAS wild-type (54 vs. 28.5%), non-codon 61 RAS-mutated (35.6%), BRAF V600E-mutated (25%), and RAS/BRAF wild-type (20.5%) cohorts. At a median follow up of 96.2 months, the median OS for codon 61 RAS-mutated patients was significantly shorter compared to RAS/BRAF wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 RAS-mutated and BRAF V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 RAS mutations and metastatic involvement of the peritoneum and ovary.

Theranostics revolution in prostate cancer: Basics, clinical applications, open issues and future perspectives.

In the last years, theranostics has expanded the therapeutic options available for prostate cancer patients. In this review, we explore this dynamic field and its potential to revolutionize precision medicine for prostate cancer. We delve into the foundational principles, clinical applications, and emerging opportunities, emphasizing the potential synergy between radioligand therapy and other systemic treatments. Additionally, we address the ongoing challenges, including optimizing patient selection, assessing treatment responses, and determining the role of theranostics within the broader landscape of prostate cancer treatment.

The Role of the Complement in Clear Cell Renal Carcinoma (ccRCC)-What Future Prospects Are There for Its Use in Clinical Practice?

In recent years, the first-line available therapeutic options for metastatic renal cell carcinoma (mRCC) have radically changed with the introduction into clinical practice of new immune checkpoint inhibitor (ICI)-based combinations. Many efforts are focusing on identifying novel prognostic and predictive markers in this setting. The complement system (CS) plays a central role in promoting the growth and progression of mRCC. In particular, mRCC has been defined as an "aggressive complement tumor", which encompasses a group of malignancies with poor prognosie and highly expressed complement components. Several preclinical and retrospective studies have demonstrated the negative prognostic role of the complement in mRCC; however, there is little evidence on its possible role as a predictor of the response to ICIs. The purpose of this review is to explore more deeply the physio-pathological role of the complement in the development of RCC and its possible future use in clinical practice as a prognostic and predictive factor.

2023 ASCO Genitourinary Cancers Symposium: a focus on urothelial carcinoma.

In this article, we describe the main acquisitions of urothelial carcinoma (UC) management reported at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium. A major development of this year was characterized by the confirmation of a disease-free survival advantage of adjuvant nivolumab for high-risk muscle-invasive urothelial carcinoma after radical resection at longer follow-up. In the metastatic setting, the updated analysis of the IMvigor130 study confirmed the failure of the strategy of adding immunotherapy (i.e. atezolizumab) to first-line chemotherapy; analogously atezolizumab monotherapy did not improve overall survival compared to chemotherapy in untreated metastatic urothelial carcinoma (mUC). Furthermore, interesting data were presented concerning future treatment options. In particular, immunotherapy (IO) with pembrolizumab showed promising activity in patients with high-risk non-muscle-invasive bladder cancer unresponsive to bacillus Calmette-Guérin (KEYNOTE-057). The antibody-drug conjugate sacituzumab govitecan demonstrated a relevant activity in platinum (PT)-ineligible mUC patients progressed after prior IO. Certainly, the lack of predictive biomarkers of response to a specific therapy highlights the urgent need for comprehensive characterization of UC for a personalized therapeutic approach that will improve patient outcomes.

Maintenance strategies after anti-EGFR-based induction in metastatic colorectal cancer: A systematic review and bayesian network meta-analysis.

BACKGROUND: In RAS wild type (wt) metastatic colorectal cancer (mCRC) maintenance therapy after induction with fluoropyrimidine (FP)-based cytotoxic therapy (CT) plus anti-EGFR agents is controversial. METHODS: Phase II-III randomized trials were included. Maintenance strategies considered were: observation, anti-EGFR or FP monotherapy, FP + anti-EGFR, doublet CT + anti-EGFR. RESULTS: Maintenance with FP + anti-EGFR (HR 0.56, 95% CrI 0.36-0.89) showed the greatest PFS benefit compared to observation, ranking first on SUCRA analysis (96.4%). Considering OS, doublet CT+ anti-EGFR, FP + anti-EGFR and anti-EGFR monotherapy yielded similar results. For PFS, FP + anti-EGFR confirmed to be valuable in BRAF wt patients and left sided tumors. In left sided tumors, the OS benefit of adding CT was limited. FP plus anti-EGFR showed a favourable safety profile compared to doublet CT + anti-EGFR. CONCLUSIONS: FP + anti-EGFR can be considered a valuable maintenance option in RAS wt mCRC. EGFR monotherapy can be considered, especially in left-sided tumors.

BNT162b2 COVID-19 Vaccine Safety among Healthcare Workers of a Tertiary Hospital in Italy.

Millions of people have died because of the COVID-19 pandemic. The vaccination campaign helped tackle the pandemic and saved millions of lives. In a retrospective pharmacovigilance study, we explored the safety of the BNT162b2 (Comirnaty) vaccine among healthcare workers (HCWs) in a large Italian teaching hospital, and 2428 Adverse Events Reports (AERs) filed by HCWs after the administration of the first dose of vaccine were collected and analyzed, reporting the results quantitively and comparing them to the vaccine Summary of Product Characteristics (SPC). Spearman's correlation coefficients were computed to investigate the correlation among reported adverse effects, and recurrent clusters of symptoms were investigated through the Principal Component Analysis (PCA) and k-means Cluster Analysis. The BNT162b2 vaccine's safety profile was favorable, with predominant reports of early onset, mild, non-serious and short-term resolved symptoms. We observed higher than the expected frequency for various non-serious undesirable effects, especially among those listed and classified as less common in the SPC. Furthermore, we identified three clusters of adverse effects that were frequently reported together, defined by the presence/absence of fatigue, malaise, localized pain, chills, pyrexia, insomnia, nausea and injection site pain. Post-marketing pharmacovigilance activities, together with targeted public health interventions, can be valuable tools to promote vaccination and improve the control of the spread of the pandemic, especially in sensitive settings and populations such as hospitals and healthcare professionals.

Knowledge and beliefs about vaccination in pregnant women before and during the COVID-19 pandemic.

Introduction: Vaccine hesitancy threatens the health of populations and challenges Public Health professionals. Strategies to reduce it aim to improve people's risk perception about vaccine-preventable diseases, fill knowledge gaps about vaccines and increase trust in healthcare providers. During pregnancy, educational interventions can provide a proper knowledge about safety and efficacy of maternal and childhood vaccinations. Fighting hesitancy and clarifying doubts is fundamental during the COVID-19 pandemic, which may have affected people's knowledge and beliefs toward vaccination. This study aimed at assessing if the advent of the pandemic was associated with changes in pregnant women's knowledge and beliefs toward vaccination, and trust in healthcare services. Methods: A repeated cross-sectional study was conducted through self-reported questionnaires in a Roman teaching hospital, where educational classes about vaccinations are routinely held as part of a birthing preparation course. Data were collected on a sample of pregnant women before and during the pandemic. Free-of-charge flu vaccinations were offered to all course participants and adherence to flu vaccination was assessed. Results: The proportion of pregnant women reporting that vaccines have mild side effects and that are sufficiently tested increased from 78.6 to 92.0% (p = 0.001) and from 79.4 to 93.2% (p = 0.001), respectively. There was a reduction from 33.0 to 23.3% (p = 0.065) in the proportion of those declaring that healthcare workers (HCWs) give information only on the benefits and not on the risks of vaccines, and a reduction from 27.3 to 12.1% (p = 0.001) in those reporting that vaccines are an imposition and not a free choice of mothers. Trust in National Health Service (NHS) operators slightly decreased. Among participants, the monthly flu vaccination adherence ranged from 50.0% in November to 29.2% January for 2019-20 flu season, and from 56.3% in September to 14.5% in January for 2020-21 flu season, showing a higher vaccination acceptance in the earlier months of 2020-21 flu season. Conclusions: The pandemic may have positively affected pregnant women's knowledge and opinions about vaccinations and trust in HCWs, despite a possible negative impact on their perceptions about NHS operators. This should inspire Public Health professionals to rethink their role as health communicators.

Is COVID-19 a Real Incentive for Flu Vaccination? Let the Numbers Speak for Themselves.

Seasonal flu vaccination is one of the most important strategies for preventing influenza. The attitude towards flu vaccination in light of the COVID-19 pandemic has so far been studied in the literature mostly with the help of surveys and questionnaires. Whether a person chooses to be vaccinated or not during the COVID-19 pandemic, however, speaks louder than any declaration of intention. In our teaching hospital, we registered a statistically significant increase in flu vaccination coverage across all professional categories between the 2019/2020 and the 2020/2021 campaign (24.19% vs. 54.56%, p < 0.0001). A linear regression model, based on data from four previous campaigns, predicted for the 2020/2021 campaign a total flu vaccination coverage of 30.35%. A coverage of 54.46% was, instead, observed, with a statistically significant difference from the predicted value (p < 0.0001). The COVID-19 pandemic can, therefore, be considered as an incentive that significantly and dramatically increased adherence to flu vaccination among our healthcare workers.

Enhancement of Vaccination Attitude and Flu Vaccination Coverage among Pregnant Women Attending Birthing Preparation Course.

Most vaccinations are recommended within the 15th month of life, in order to reduce risks and to protect children from the initial stages of their lives. A vaccination training session was carried out during the birthing preparation course, aimed at increasing the attitude toward vaccination in maternal-child age. A questionnaire on vaccination awareness was administered before and after the training session and on-site flu vaccination was offered to women and their companions. The percentage of participants who consider the preparatory course a useful tool to obtain information about vaccines increases significantly from 30.34% at pre-intervention to 64.56% at post-intervention (p < 0.001). There is a significant increase in the mean number of vaccinations that the participants want their children to get. The number of participants believing that there is no relationship between vaccination and autism rose from 41.05 to 72.97% (p < 0.001). In total, 48 out of 119 (40.34%) pregnant women participating in the course and 39 companions were vaccinated for influenza. Vaccination knowledge and attitude significantly increased after a training session dedicated to vaccination as a part of the pregnant pre-birth course, whose aim can be therefore extended to the management of the health of the child, well beyond the period of pregnancy, according to the life-course approach to health.