Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear. Limited consensus exists regarding tailored treatments for SPOP-mutant (SPOPmut) PC. To elucidate the prognostic and predictive significance of SPOP mutations across distinct PC stages and treatments. A systematic literature search of PubMed, Embase, and Scopus was conducted up to January 29, 2024. The meta-analysis included studies comparing survival outcomes between SPOPmut and SPOP wild-type (SPOPwt) PC. From 669 records, 26 studies (including five abstracts) were analyzed. A meta-analysis of metastasis-free survival in localized (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; p < 0.01) and overall survival (OS) in metastatic PC (HR: 0.64, 95% CI: 0.53-0.76; p < 0.01) showed a favorable prognosis for patients with SPOPmut PC. In metastatic settings, SPOP mutations correlated with improved progression-free survival (PFS) and OS in patients undergoing androgen deprivation therapy ± androgen receptor signaling inhibitor (HR: 0.51, 95% CI: 0.35-0.76, p < 0.01, and HR: 0.60, 95% CI:0.46-0.79, p < 0.01, respectively). In metastatic castration-resistant PC, only abiraterone provided improved PFS and OS to patients with SPOP mutations compared with patients with SPOPwt, but data were limited. SPOP mutations did not correlate with improved PFS (p = 0.80) or OS (p = 0.27) for docetaxel. Patients with SPOPmut PC seem to exhibit superior oncological outcomes compared with patients with SPOPwt. Tailored risk stratification and treatment approaches should be explored in such patients. Speckle-type POZ (SPOP) mutations could be a favorable prognostic factor in patients with prostate cancer (PC) and may also predict better progression-free and overall survival than treatment with hormonal agents. Therefore, less intensified treatments omitting chemotherapy for patients with SPOP-mutant PC should be explored in clinical trials.

Background: The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC). Methods: A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Results: After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71–4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors. Conclusions: While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.

Aggressive variant prostate cancer (AVPC) is characterized by a molecular signature involving combined defects in TP53, RB1, and/or PTEN (AVPC-TSGs), identifiable through immunohistochemistry or genomic analysis. The reported prevalence of AVPC-TSG alterations varies widely, reflecting differences in assay sensitivity, treatment pressure, and disease stage evolution. Although robust clinical evidence is still emerging, the study of AVPC-TSG alterations in prostate cancer (PCa) is promising. Alterations in TP53, RB1, and PTEN, as well as the combined loss of AVPC-TSGs, may have significant implications for prognosis and treatment. These biomarkers might help predict responses to various therapies, including hormonal treatments, cytotoxic agents, radiotherapy, and targeted therapies. Understanding the impact of these molecular alterations in patients with PCa is crucial for personalized management. In this review, we provide a comprehensive overview of the emerging prognostic and predictive roles of AVPC-TSG alterations across PCa stages. Moreover, we discuss the implications of different methods used for detecting AVPC-TSG alterations and summarize factors influencing their prevalence. As our comprehension of the genomic landscape of PCa disease deepens, incorporating genomic profiling into clinical decision making will become increasingly important for improving patient outcomes.

Background: In 2019, the breakthrough of the coronavirus 2 disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represented one of the major issues of our recent history. Different drugs have been tested to rapidly find effective anti-viral treatments and, among these, antiandrogens have been suggested to play a role in mediating SARS-CoV-2 infection. Considering the high heterogeneity of studies on this topic, we decided to review the current literature. Methods: We performed a systematic review according to PRISMA guidelines. A search strategy was conducted on PUBMED and Medline. Only original articles published from March 2020 to 31 August 2023 investigating the possible protective role of antiandrogens were included. In vitro or preclinical studies and reports not in the English language were excluded. The main objective was to investigate how antiandrogens may interfere with COVID-19 outcomes. Results: Among 1755 records, we selected 31 studies, the majority of which consisted of retrospective clinical data collections and of randomized clinical trials during the first and second wave of the COVID-19 pandemic. Conclusions: In conclusion, we can state that antiandrogens do not seem to protect individuals from SARS-CoV-2 infection and COVID-19 severity and, thus, their use should not be encouraged in this field.

Alterations in aggressive-variant prostate cancer-associated tumor suppressor genes (AVPC-TSG: TP53, RB1, PTEN) are related with androgen insensitivity and aggressive disease. However, their prognostic and predictive role in metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. This single-center retrospective study assesses the value of AVPC-TSG alterations in refining prognosis and predicting the response to androgen receptor pathway inhibitors (ARPIs) in mHSPC. We included 158 patients with genomic tumor sequencing undergoing treatment for mHSPC between 2013 and 2023. We compared patients with AVPC-TSGalt tumors (≥1 alteration in TP53, RB1, or PTEN/PI3K/AKT pathway genes) to those with AVPC-TSGwt tumors (i.e., without alterations in AVPC-TSG). Cox analyses were performed for progression-free survival (PFS) and overall survival (OS). AVPC-TSGwt status was associated with improved PFS and OS in both univariate and multivariate (MV) analyses (MV PFS: HR 0.58, 95%CI: 0.38–0.89, p = 0.012; MV OS: HR 0.48, 95%CI: 0.26–0.91, p = 0.025). AVPC-TSGalt mHSPC patients seemed to derive no PFS benefit from ARPI addition (PFS: HR 1.13, 95%CI: 0.58–2.19, p = 0.721), while AVPC-TSGwt mHSPC patients did (PFS: HR 0.51, 95%CI: 0.28–0.93 p = 0.029). Integrating AVPC-TSG status with CHAARTED volume criteria, we identified three distinct subgroups: “good risk” (AVPC-TSGwt low volume), “intermediate risk” (either AVPC-TSGalt low volume or AVPC-TSGwt high volume), and “poor risk” (AVPC-TSGalt high volume) with median PFS of 46.8, 28.2, and 15.7 months, respectively. Only the “intermediate risk” subgroup seemed to derive PFS benefit from ARPI addition (HR 0.36, 95%CI: 0.19–0.70, p = 0.002). AVPC-TSG status assessment refines prognosis and may predict PFS benefits of ARPIs in mHSPC. AVPC-TSGalt mHSPC patients should be considered for clinical trials as they may not benefit from current standard approaches.

Aggressive-variant prostate cancer (AVPC) is an umbrella term that encompasses clinically defined AVPC (c-AVPC), molecularly defined AVPC (m-AVPC), and treatment-related neuroendocrine PC (t-NEPC), which represent a spectrum of metastatic castration-resistant PC phenotypes with poor clinical outcomes. Despite its clinical relevance, AVPC definitions remain heterogeneous and treatment guidelines are lacking. Our aim was to elucidate AVPC prognosis and treatment responsiveness across definitions. We conducted a systematic literature search of PubMed, Embase, and Scopus up to September 15, 2025. Our meta-analysis included studies reporting survival outcomes and treatment responses for patients with AVPC. From 1518 records, 40 studies (including 10 abstracts) were analyzed. In comparison to non-AVPC, c-AVPC/m-AVPC was associated with shorter progression-free survival (PFS; hazard ratio [HR] 2.72, 95% confidence interval [CI] 1.54-4.81; I² = 0%) and overall survival (OS; HR 2.81, 95% CI 1.87-4.22; I² = 36%). Platinum-based chemotherapy (PBC) outperformed non-platinum regimens, with higher objective response rates in the overall AVPC cohort (46% vs 19%; p < 0.01) and in the c-AVPC/m-AVPC (41% vs 16%; p = 0.04) and t-NEPC (49% vs 22%; p < 0.01) subgroups. In c-AVPC/m-AVPC, PBC was associated with longer PFS (HR 0.39, 95% CI 0.24-0.62; I² = 0%) and OS (HR 0.40, 95% CI 0.23-0.68; I² = 0%) according to evidence from mixed-design studies. For t-NEPC, data were insufficient for meta-analytic comparison of PFS and OS by PBC use. AVPC encompasses distinct subsets of advanced PC that are associated with higher risk of progression and death on standard PC therapies. Platinum-based chemotherapy was associated with better response rates across AVPC subtypes and appears to confer a survival benefit in c-AVPC and m-AVPC. Future studies should focus on molecularly informed classification frameworks that include genomics, histology, and advanced imaging to optimize patient stratification and guide targeted therapies.