Search

Despite advances in prostate cancer screening and treatment, available therapy options, particularly in later stages of the disease, remain limited and the treatment-resistant setting represents a serious unmet medical need. Moreover, disease heterogeneity and disparities in patient access to medical advances result in significant variability in outcomes across patients. Disease classification based on genomic sequencing is a promising approach to identify patients whose tumors exhibit actionable targets and make more informed treatment decisions. Here we discuss how we can accelerate precision oncology to inform broader genomically-driven clinical decisions for men with advanced prostate cancer, drug development and ultimately contribute to new treatment paradigms.

The development of large language models (LLMs) is a recent success in the field of generative artificial intelligence (AI). They are computer models able to perform a wide range of natural language processing tasks, including content generation, question answering, or language translation. In recent months, a growing number of studies aimed to assess their potential applications in the field of medicine, including cancer care. In this mini review, we described the present published evidence for using LLMs in oncology. All the available studies assessed ChatGPT, an advanced language model developed by OpenAI, alone or compared to other LLMs, such as Google Bard, Chatsonic, and Perplexity. Although ChatGPT could provide adequate information on the screening or the management of specific solid tumors, it also demonstrated a significant error rate and a tendency toward providing obsolete data. Therefore, an accurate, expert-driven verification process remains mandatory to avoid the potential for misinformation and incorrect evidence. Overall, although this new generative AI-based technology has the potential to revolutionize the field of medicine, including that of cancer care, it will be necessary to develop rules to guide the application of these tools to maximize benefits and minimize risks.

The risks of development of colorectal and endometrial cancers in individuals with Lynch syndrome (LS) are well known and have been widely studied. In recent years, the potential association of other malignancies, including prostate cancer, with LS has been considered. Decision-making regarding screening for prostate cancer in the generalized population can be complicated; accounting for the possibility of a higher risk of cancer conferred by a potential genetic predisposition confounds the creation of salient guidelines even further. Although tissue-agnostic treatment approvals have been granted to several immune checkpoint inhibitors (ICIs) for their use in the treatment of subsets of patients whose tumors exhibit high levels of microsatellite instability or high tumor mutational burden, a paucity of data exists regarding the use of ICIs in the first line treatment of patients with locally advanced prostate cancer harboring these features. A significant reduction in tumor volume in response to the combination of immune checkpoint inhibition and androgen deprivation therapy is described in this report of a male with Muir-Torre syndrome who was found to have locally advanced adenocarcinoma of the prostate. While anecdotal, the anti-tumor activity of this combination of therapy is notable and calls attention to the importance of considering further investigation of the use of immune checkpoint blockade as a primary therapeutic option in patients with localized prostate cancer.

Despite the clinical advances in managing metastatic prostate cancer in the last 20 years, treatments for patients with metastatic disease only offer a brief respite from disease progression, especially after first-line therapies. Research into treatment resistance has defined a subset of patients with neuroendocrine differentiation of their prostate adenocarcinoma. Although neuroendocrine findings in conjunction with prostate adenocarcinoma can be seen in pathology samples at all stages of disease, the neuroendocrine variant of prostate cancer associated with poor outcomes occurs in approximately 20% of men with advanced disease. In this issue of JCI, Zhao, Sperger, and colleagues present data for a promising biomarker platform that can detect neuroendocrine prostate cancer after serial sampling of patients’ blood with a high degree of sensitivity and specificity. This assay will be tested in several current and future trials to better define its potential clinical role and perhaps provide a greater understanding of neuroendocrine prostate cancer itself.

Despite the clinical advances in managing metastatic prostate cancer in the last 20 years, treatments for patients with metastatic disease only offer a brief respite from disease progression, especially after first-line therapies. Research into treatment resistance has defined a subset of patients with neuroendocrine differentiation of their prostate adenocarcinoma. Although neuroendocrine findings in conjunction with prostate adenocarcinoma can be seen in pathology samples at all stages of disease, the neuroendocrine variant of prostate cancer associated with poor outcomes occurs in approximately 20% of men with advanced disease. In this issue of JCI, Zhao, Sperger, and colleagues present data for a promising biomarker platform that can detect neuroendocrine prostate cancer after serial sampling of patients' blood with a high degree of sensitivity and specificity. This assay will be tested in several current and future trials to better define its potential clinical role and perhaps provide a greater understanding of neuroendocrine prostate cancer itself., Diagnosing neuroendocrine prostate cancer The last two decades have seen a remarkable expansion of therapeutic options that improve survival for men with metastatic prostate cancer, yet, for most patients, these [...]

Background We described participant demographics for National Cancer Institute (NCI) clinical trials at the clinical center (NCI-CC participants) of the National Institutes of Health to identify enrollment disparities. Methods We analyzed NCI-CC data from 2005 to 2020, calculated enrollment fractions, compared with the US cancer population represented by the Surveillance, Epidemiology, and End Results cancer incidence data (2018) and the Cancer in North America database (2018), and compared further with clinical trial disparities data from the NCI Community Oncology Research Program and National Clinical Trials Network (2005-2019), and from ClinicalTrials.gov (2003-2016). Results NCI-CC (38 531 participants) had higher enrollment fractions for older adults (8.5%), male (5.6%), non-Hispanic (5.1%), and Black or African American (5.3%) participants; lower women proportion across race and ethnicity; and fewer female sex-specific cancer (6.8%) than male sex-specific cancer (11.7%) participants. NCI-CC had lower median age than Surveillance, Epidemiology, and End Results (54.0 vs 65.4); more Black or African American participants (12.0% vs 11.1%); and fewer women (41.7% vs 49.5%), White (76.1% vs 80.5%), Asian or Pacific Islander (4.6% vs 6.0%), American Indian or Alaska Native (0.3% vs 0.5%), and Hispanic participants (7.1% vs 13%). NCI-CC had more Black or African American and Asian or Pacific Islander participants; fewer Hispanic participants than the NCI Community Oncology Research Program and National Clinical Trials Network; more Black or African American and Hispanic participants; fewer Asian or Pacific Islander participants than ClinicalTrials.gov data. Improvement was noted for NCI-CC (older adults, Black or African American, Asian or Pacific Islander, Hispanic participants). Conclusion We found lower representation of older adults, women, Asian or Pacific Islander, American Indian or Alaska Native, and Hispanic participants vs the US cancer population and higher representation of Black or African American vs US cancer population and oncology clinical trials. Multifaceted efforts are underway to reduce disparities in cancer clinical trials at the NCI-CC. [ABSTRACT FROM AUTHOR]

Prostate cancer is often a multifocal disease but how best to manage this clinically remains unclear. Here, the authors report a single case study of a patient with two genetically diverse tumours which showed differential response to therapy.

The article comments on the difference of large cell neuroendocrine prostate cancer (LCPC) from small-cell neuroendocrine carcinoma (SCPC) ). It clarifies that neuroendocrine differentiation does not imply small cell or large cell carcinoma. It offers treatment recommendations for LCPC, a guide for histologic diagnosis of SCPC and LCPC, and recommendations for immunohistochemical diagnosis of SCPC and LCPC and for future investigation of LCPC.