Prostate cancer is the most common cancer and second leading cause of cancer-related death in American men. Antiandrogen therapies are part of the standard of therapeutic regimen for advanced or ...metastatic prostate cancers; however, patients who receive these treatments are more likely to develop castration-resistant prostate cancer (CRPC) or neuroendocrine prostate cancer (NEPC). In the development of CRPC or NEPC, numerous genetic signaling pathways have been under preclinical investigations and in clinical trials. Accumulated evidence shows that DNA methylation, chromatin integrity, and accessibility for transcriptional regulation still play key roles in prostate cancer initiation and progression. Better understanding of how epigenetic change regulates the progression of prostate cancer and the interaction between epigenetic and genetic modulators driving NEPC may help develop a better risk stratification and more effective treatment regimens for prostate cancer patients.
•Patients who receive antiandrogen treatments are more likely to develop CRPC.•A genomic landscape study has identified aberrant epigenetic events in CRPC and NEPC development.•Epigenetic targeting may represent an alternative therapeutic regimen for advanced prostate cancer.•Ongoing preclinical and clinical trials have shed light on the advantage of combination therapies.
Highlights • Evasion of immune surveillance, a process defined immune-editing, leads to RCC malignant progression. • The PD-1/PD-L1 axis inhibition by targeted-antibodies, increases T-cell ...proliferation and anti-tumor activity. • PD-1 and PD-L1 inhibitors have been tested in RCC, alone or combined with anti-VEGF/VEGFR drugs or other immunotherapies. • We discuss the role of PD-1/PD-L1 in RCC, focusing on current clinical studies and future perspectives.
The International Society of Urological Pathology held a conference devoted to issues in testicular and penile pathology in Boston in March 2015, which included a presentation and discussion led by ...the testis microscopic features working group. This conference focused on controversies related to staging and reporting of testicular tumors and was preceded by an online survey of the International Society of Urological Pathology members. The survey results were used to initiate discussions, but decisions were made by expert consensus rather than voting. A number of recommendations emerged from the conference, including that lymphovascular invasion (LVI) should always be reported and no distinction need be made between lymphatic or blood invasion. If LVI is equivocal, then it should be regarded as negative to avoid triggering unnecessary therapy. LVI in the spermatic cord is considered as category pT2, not pT3, unless future studies provide contrary evidence. At the time of gross dissection, a block should be taken just superior to the epididymis to define the base of the spermatic cord, and direct invasion of tumor in this block indicates a category of pT3. Pagetoid involvement of the rete testis epithelium must be distinguished from rete testis stromal invasion, with only the latter being prognostically useful. Percentages of different tumor elements in mixed germ cell tumors should be reported. Although consensus was reached on many issues, there are still areas of practice that need further evidence on which to base firm recommendations.
Bladder cancer is a heterogeneous disease with a variable natural history. At one end of the spectrum, low-grade Ta tumors have a low progression rate and require initial endoscopic treatment and ...surveillance but rarely present a threat to the patient. At the other extreme, high-grade tumors have a high malignant potential associated with significant progression and cancer death rates. In the Western world, bladder cancer is the fourth most common malignancy in men and the eighth most common in women. In Europe and the United States, bladder cancer accounts for 5% to 10% of all malignancies in men. The risk of developing bladder cancer at <75 years of age is 2% to 4% for men and 0.5% to 1% in women compared with the risk of lung cancer, for example, which is 8% in men and 2% in women. For the geographic and temporal comparison of bladder cancer incidence, it is crucial to separate the low-grade from the high-grade tumors. In epidemiologic studies on risk factors for bladder cancer, it is important to distinguish the low-grade Ta tumors from high-grade carcinoma in situ (CIS) and tumors >T1. Current studies do not support the routine screening for bladder cancer. However, prospective long-term studies are required to evaluate the benefits of bladder cancer screening, particularly in those at high risk. After assessing all available evidence, the Epidemiology and Diagnosis Committee has made recommendations on various diagnostic issues, including pathologic evaluation, urinary cytology, and imaging studies. Optimal resection techniques, role of repeat transurethral resection in high-grade T1 tumors, random bladder biopsy, and prostatic urethral biopsy are discussed, and appropriate recommendations are made according to the strength of available evidence.
Introduction: Tumor development results from a cancer-induced immunosuppression (immune-editing). Immunotherapy has revolutionized the treatment paradigm for many malignancies, putting clinicians ...before novel toxicities, of immune-mediated etiology (immune-related adverse events).
Areas covered: Immune-mediated toxicity depends on both innate and adaptive immunity mechanisms. Healthy tissue damage depends on an aspecific T-cell hyperactivation response causing cross-reaction with normal tissues, which leads to an overproduction of CD4 T-helper cell cytokines and an abnormal migration of cytolytic CD8 T-cells. By stimulating a diffuse T-cell repertoire expansion, immune-checkpoint inhibitors counteract tumor growth but reduce the self-tolerance, damaging healthy organs. In this review, we summarize the toxicity profile of the novel immune-checkpoint inhibitors and their clinical implications, we are convinced that a deep understanding and a prompt resolution of the paradigmatic toxicities of these drugs will result in clinical benefits to patients and an enhanced antitumor effect.
Expert opinion: A focus on immunotoxicity is important in the education of clinicians and will improve patient safety. There is a willingness to tailor specific immune-therapies to each cancer patient, and to stimulate researchers through understanding of the physiopathogenesis, using the hypothesis that immune-mediated toxicities can be used as predictors of response or a prognostic sign of survival, thereby guiding therapeutic decisions.
Currently, sunitinib represents one of the therapeutic strongholds for renal cell carcinoma, but the criteria for treatment selection are lacking. We assessed the role of vascular endothelial growth ...factor (VEGF) and VEGF receptor (VEGFR) polymorphisms in the prediction of the clinical outcome in metastatic renal cell carcinoma (mRCC) patients.
A total of 84 tumour samples from mRCC patients receiving first-line sunitinib were tested for VEGF and VEGFR single-nucleotide polymorphisms (SNPs). The SNP results were correlated with progression-free survival (PFS) and overall survival (OS).
Median PFS was 8.22 months, although whereas median OS was 32.13 months. The VEGF A rs833061 resulted significant in PFS (17 vs 4 months; P<0.0001) and OS (38 vs 10 months; P<0.0001). The VEGF A rs699947 was significant for PFS (18 vs 4 months; P=0.0001) and OS (37 vs 16 months; P<0.0001). The VEGF A rs2010963 was significant in PFS (18 vs 8 vs 2 months; P=0.0001) and OS (31 vs 36 vs 9 months; P=0.0045). The VEGR3 rs6877011 was significant in PFS (12 vs 4 months; P=0.0075) and OS (36 vs 17 months; P=0.0001). At multivariate analysis, rs833061, rs2010963 and rs68877011 were significant in PFS, and rs833061 and rs68877011 were independent factors in OS.
In our analysis, patients with TT polymorphism of rs833061, CC polymorphism of rs699947, CC polymorphism of rs2010963 and CG polymorphism of rs6877011 seem to have a worse PFS and OS when receiving first-line sunitinib.
We have witnessed successive stages since the Seventies in the advancements towards digital pathology. We agree with Dr Pallua et al on the tremendous changes that are taking place in pathology, all ...leading toward greater role of digitalization in the field of pathology, both in terms of consultation and teaching. In particular, distance teaching using digital pathology will grow into a mainstream mode of pathology teaching, something that has been reinforced by COVID-19.
Purpose
To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method.
Methods
A panel of international experts in the field of ...focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings.
Results
Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 Gleason score (GS) 3+4. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation.
Conclusion
Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.
Prostate-specific membrane antigen (PSMA) is an integral, non-shed membrane glycoprotein that is highly expressed on prostate epithelial cells and strongly upregulated in prostate cancer (PCa). ...Prostatic neoplastic transformation results in the transfer of PSMA from the apical membrane to the luminal surface of the ducts. However, the role of PSMA in tumor angiogenesis and carcinogenesis is poorly understood. PSMA is characterized by folate hydrolase and carboxypeptidase activity and internalization function, and its levels are directly correlated to androgen independence, metastasis and PCa progression. As largely substantiated by preclinical and clinical findings, PSMA could represent a promising target for Positron Emission Tomography (PET) radiopharmaceuticals for PCa imaging. Furthermore, PSMA could prove an important target for the development of new therapeutic approaches, including PSMA-based aptamers, peptides, antibody-drug conjugated therapy, as well as radiotherapy and immunotherapy. This review will summarize the role of PSMA in PCa development and progression and its potential role in the diagnosis and treatment of patients with initial and advanced PCa.
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