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1.
BJU Int ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32401370

RESUMO

Intra-operative tailoring of surgical dissection during radical prostatectomy (RP) can be performed with the help of either 3D-augmented reality or frozen section analysis [1]. The latter with the purpose of maximizing nerve-sparing (NS) RP has evolved into the NeuroSAFE, a dissection technique of the prostatic surface limited to the neurovascular(NV)-structure-adjacent-prostatic-tissue aiming to detect cancer persisting at the NV-area [2].

2.
Curr Drug Targets ; 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386490

RESUMO

Five programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for the treatment of locally advanced or metastatic urothelial carcinoma of the bladder and the upper urinary tract. Following the FDA and EMA restrictions of first-line treatment with Atezolizumab and Pembrolizumab in platinum-ineligible patients, immunohistochemical PD-L1 testing is now required. Several emerging issues on antibodies, test platforms and scoring algorithms have raised concerns about the comparability and interchangeability between these assays. In this review we have focused on the interchangeability of the used algorithms and assays for PD-L1 testing in urothelial carcinoma, on the predictive reliability of PD-L1 testing in urothelial carcinoma and the potential of other new and upcoming biomarkers.

3.
Int J Biol Markers ; : 1724600820919969, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32389051

RESUMO

BACKGROUND: The PreImplantation Factor (PIF)-a peptide secreted by viable embryos-exerts autotrophic protective effects, promotes endometrial receptivity and controls trophoblast invasion. Synthetic PIF (sPIF) has both immune-protective and regenerative properties, and reduces oxidative stress and protein misfolding. PIF is detected by immunohistochemistry (IHC) in hyperplastic endometriotic lesions and advanced uterine cancer. sPIF reduces graft-versus-host disease while maintaining a graft-versus-leukemia effect. METHODS: PIF detection in prostate cancer was assessed in 50 human prostate samples following radical prostatectomy using tumor-microarray-based IHC correlating PIF immune staining with Gleason score (GS) and cancer aggressiveness. RESULTS: PIF was detected in moderate-to-high risk prostate cancer (GS 4+3 and beyond, prognostic groups 3 to 5). In prostate cancer (GS (WHO Grade Group (GG)5), PIF was detected in 50% of cases; in prostate cancer (GS 4+4 GG4), PIF was observed in 62.5% of cases; in prostate cancer (GS 4+3 GG3), PIF immunostaining was observed in 57.1% of cases. In prostate cancer, (GS 3+4 GG2) and (GS 3+3 GG1) cases where PIF staining was negative to weak, membranous staining was observed in 20% of cases (staining pattern considered negative). High-grade prostate intraepithelial neoplasia PIF positive stain in 28.57% of cases (6 of 21) was observed. In contrast, PIF was not detected in normal prostate glands. Importantly, sPIF added to the PC3 cell line alone or combined with prostate cancer fibroblast feeder-cells did not affect proliferation. Only when peripheral blood mononuclear cells were added to the culture, a minor increase in cell proliferation was noted, reflecting local proliferation control. CONCLUSIONS: Collectively, PIF assessment could be a valuable, simple-to-use immunohistochemical biomarker to evaluate aggressiveness/prognosis in specimens from prostate cancer patients.

5.
Eur Urol Oncol ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32303478

RESUMO

CONTEXT: Intermediate-risk prostate cancer consists of a highly heterogeneous group of patients. Owing to this heterogeneity and variable prognoses, it is challenging to provide uniform treatment recommendations for men in this group. OBJECTIVE: To review the current literature regarding the best available evidence for stratification and treatment of intermediate-risk prostate cancer patients. EVIDENCE ACQUISITION: We searched Medline and EMBASE, through September 2019 without year or language restriction, supplemented with hand search. EVIDENCE SYNTHESIS: Different treatment options with good long-term oncological outcomes are available for intermediate-risk prostate cancer patients. Best available evidence with long follow-up exists for radical prostatectomy and dose-escalated radiotherapy with short-term androgen deprivation. In favorable intermediate-risk patients, active surveillance and brachy-monotherapy also represent two valid treatment options. In carefully selected men, partial gland ablation represents a reasonable option. Patient preferences and comorbidities should also be considered. CONCLUSIONS: Treatment options for intermediate-risk patients range from active surveillance to partial gland ablation, radical prostatectomy, and various radiotherapy methods. The best stratification and the optimal treatment remain controversial. Classification systems, such as the National Cancer Comprehensive Network guidelines, stratify this large cohort into subgroups with favorable or unfavorable disease, which may simplify treatment recommendations but still leave substantial variability within strata. Advanced imaging may further improve current stratification systems of intermediate-risk patients. PATIENT SUMMARY: In this review, we assessed the current literature regarding the best available evidence for stratification and treatment of intermediate-risk prostate cancer patients.

6.
Cells ; 9(5)2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32344931

RESUMO

The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a rapidly progressive disease course. This involves hormone refractoriness and metastasis in visceral sites. Morphologically, AVPCa is made up of solid sheets of cells devoid of pleomorphism, with round and enlarged nuclei with prominent nucleoli and slightly basophilic cytoplasm. The cells do not show the typical architectural features of prostatic adenocarcinoma and mimic the undifferentiated carcinoma of other organs and locations. The final diagnosis is based on the immunohistochemical expression of markers usually seen in the prostate, such as prostate-specific membrane antigen (PSMA). A subset of AVPCa can also express neuroendocrine (NE) markers such as chromogranin A, synaptophysin and CD56. This letter subset represents an intermediate part of the spectrum of NE tumors which ranges from small cell to large cell carcinoma. All such tumors can develop following potent androgen receptor pathway inhibition. This means that castration-resistant prostate cancer (CRPCa) transdifferentiates and becomes a treatment-related NE PCa in a clonally divergent manner. The tumors that do not show NE differentiation might harbor somatic and/or germline alterations in the DNA repair pathway. The identification of these subtypes has direct clinical relevance with regard to the potential benefit of platinum-based chemotherapy, poly (ADP-ribose) polymerase inhibitors and likely further therapies.

7.
Virchows Arch ; 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296929

RESUMO

Most patients with bladder carcinoma are diagnosed with non-muscle-invasive disease, stage Ta, and pT1. Stage remains as the single most important prognostic indicator in urothelial carcinoma. Among the pT1 bladder cancer patients, recurrence and progression of disease occur in 50% and 10%, respectively. The identification of high-risk patients within the pT1 subgroup remains an important clinical goal and an active field of research. Substaging of pT1 disease has been claimed as important histologic discriminator by the 2016 World Health Organization (WHO) classification of the genitourinary tract tumors and by the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual supporting its implementation in clinical practice. Interobserver variation in pT1 diagnosis and the associated pitfalls in pT1 assessment are the critical pathological issues. The aim of this review paper is to provide the practicing pathologist with the state of the art of morphological and immunohistochemical features useful for the diagnosis of early invasive bladder carcinomas, including practical clues on how to avoid relevant interpretative pitfalls, and to summarize the current status of pT1 substaging.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32147365

RESUMO

BACKGROUND: The index lesion (IL) is the largest cancer focus, usually harbors the highest grade, and might drive the history of prostate cancer (PCA). Multiparametric magnetic resonance imaging (mp-MRI) has a high negative predictive value in ruling out clinically significant (cs)PCA. We aimed evaluating the efficiency of mp-MRI and targeted biopsy in detecting csPCA and the concordance between the MRI index lesion (MRI-IL) and the presence of csPCA inside it. MATERIALS AND METHODS: We retrospectively evaluated 158 men who underwent prostate biopsy after a positive pre-biopsy mp-MRI scan. All mp-MRI lesions were biopsied using a transrectal ultrasound elastic-fusion approach (2-4 targeted plus 10-12 random systematic biopsies). csPCA was defined as grading group ≥ 2 or > 3 cores with cancer or ≥ 50% of core involved by tumor. RESULTS: mp-MRI detected 158 ILs and 46 non-ILs. One hundred were Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2) score 3, 84 score 4, and 20 score 5. csPCA was found in 63.9% of the MRI-ILs. Eighty percent of detected cancer using mp-MRI and targeted biopsy was clinically significant. Eighty-seven percent of the transitional zone lesions were clinically non-significant or negative for cancer. The probability of detecting csPCA increases with increasing size of MRI-IL, and every extra millimeter raises the odds of detecting csPCA of 12.2%. All PI-RADS v2 score lesions showed a strong association with csPCA. The risk of matching between MRI-IL and csPCA inside it increases by 36.2% as the total percentage of cancer in all cores increases. CONCLUSIONS: mp-MRI showed high sensitivity in detecting csPCA in the peripheral zone, with concordance between MRI-IL and csPCA.

10.
Curr Drug Targets ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160846

RESUMO

AIMS: The aim of our review is to explore the current knowledge on the relationship between immunotherapy and radiotherapy in renal cell carcinoma. BACKGROUND: The management of renal cell carcinoma is rapidly evolving and immunotherapy, mostly consisting in immune checkpoint inhibitors, are revolutionizing the treatment scenario of metastatic patients. Novel fractionation schedules of radiotherapy, consisting of high doses in few fractions, are able to overcome the radioresistance of this tumor. Localized radiotherapy is associated with a systemic effect, known as abscopal effect. This immune mediated effect can be enhanced with association of radiotherapy with immunotherapy. OBJECTIVE: In this review, we explore the role of radiotherapy and immunotherapy in RCC, the rationale of combining these strategies and the on-going clinical trials investigating combinations of these two treatment modalities. METHOD: We conducted a review of the recent evidences of the literature on the role of immunotherapy and radiotherapy and their relationship in the management of renal cell carcinoma. RESULT: Immunotherapy is a new cornerstone in the management of metastatic RCC. Radiotherapy can stimulate an abscopal effect. The combination of immunotherapy and radiotherapy can increase the immune response against the tumor. CONCLUSION: Combining immunotherapy and radiotherapy has a strong rationale and pre-clinical studies support their association because it can overcome the immunosuppression of the tumor microenvironment and increase the anti-tumor immune response. Other: More clinical evidences, deriving from on-clinical trials, are needed to prove the efficacy and safety of these treatments combined.

11.
Urol Oncol ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32220548

RESUMO

PURPOSE: To determine the potential role of bioptic inflammation (Irani score) in predicting adverse pathology (AP) at radical prostatectomy (RP) in patients with low-grade (ISUP Gleason Group [ISUP GG] 1 and 2) prostate cancer (CaP). METHODS: After institutional review board-approval, we identified patients who underwent prostate biopsy, had bioptic Irani score assessment, were diagnosed with low-grade CaP (ISUP GG 1-2, prostate-specific antigen [PSA] <20 ng/ml), and underwent RP. The impact of standard clinicopathological variables and bioptic Irani Score (G = grade and A = aggressiveness) on AP at RP, defined as stage ≥T3 and/or ISUP GG ≥3, was assessed by univariate and multivariate logistic regression analysis. RESULTS: A total of 282 patients were eligible for this study. AP at RP occurred in 37 of 214 (17.3%) patients with ISUP GG 1, and 26 of 68 (38.2%) with ISUP GG 2. At univariate analysis, serum PSA, PSA density, bioptic ISUP GG, number of positive cores, total percentage of core involvement and Irani G score emerged as significant risk factors of AP. At multivariate analysis, however, only PSA density, bioptic ISUP GG, total percentage of core, and Irani G score kept statistical significance. The area under the curve for the resulting model was 0.75. CONCLUSIONS: This is the first study demonstrating that low-grade inflammation is associated with a significantly increased risk of AP at RP. These findings would support the concept of prostatic inflammation being inversely correlated with presence and aggressiveness of CaP. Further studies are needed to externally validate the role of this readily available parameter in the decision-making process of patients with low-grade CaP.

14.
Curr Drug Targets ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32208115

RESUMO

BACKGROUND: Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway represents a drastic change in the treatment landscape of RCC resulting in a dynamic and evolving scenario. There is an urgent need for predictive biomarkers of response to provide a personalized therapeutic strategy for individual patients. OBJECTIVE: In this review we focused on trials that investigated the use of a PD-1 and PD-L1 inhibitor alone or in combination with another agent and compared the different assays applied in each trial to evaluate the role of PD-L1 as prognostic and predictive biomarker. Conclusion So far, data on the use of PD-L1 expression alone is not sufficient to predict treatment response and present many limitations: the lack of consensus between different methodologies on biomarker assessment, the heterogeneity of PD-L1 between primary tumors and metastatic sites, different criteria of response to therapy (RECIST vs. irRECIST), the complex interplay with inflammatory components, previous treatments, administration of an antibiotic therapy. Combinations of different biomarkers and biological features such as gene expression associated with angiogenesis, immune response and myeloid inflammation are promising biological variables that need to be validated in the context of prospective clinical trials.

15.
Curr Drug Targets ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32213156

RESUMO

The immune system is important to control tumor development and progression. However, tumor cells and cells of the tumor microenvironment can induce immune escape mechanisms including activation of immune checkpoints such as PD-1/PD-L1. Based on this knowledge, new immune therapies including PD-1 and PD-L1 inhibition have been developed and are already recommended as standard treatment in metastatic bladder and kidney cancer patients. In addition to its role as a therapeutic target PD-L1 seems to be a prognostic parameter although data are controversial. Only little is known about signaling pathways inducing PD-L1 expression in tumor cells on one hand and about its functional role for tumor cells itself. However, the understanding of the complex biological function of PD-L1 will improve therapeutic options in urological malignancies. This review is giving an overview of the current knowledge concerning the PD-1/PD-L1 axis in urological tumors including bladder, kidney, prostate, testicular and penile cancer.

18.
Minerva Urol Nefrol ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31920063

RESUMO

BACKGROUND: We assessed patients and tumor characteristics, as well as health-related quality of life (HRQoL) items, associated with curative intent treatment decision-making in clinically localized prostate cancer (PCa) patients. METHODS: Clinically localized PCa treated with either radical prostatectomy (RP) or radiation therapy (RT) within 12 months from diagnosis were abstracted from The PROState cancer monitoring in ITaly, from the National Research Council (Pros-IT CNR) database. Multivariable logistic regression (MLR) models predicting RT vs. RP were fitted, after adjustment for HRQoL items, patients and tumor characteristics. RESULTS: Of 1 041 patients, 631 (60.2%) were treated with RP and 410 (39.8%) with RT. Relative to RT, RP patients were younger age (mean age 64.5±6.6 vs. 71.4±4.9, p<0.001) and had higher rates of D'Amico low-intermediate risk groups (31.8 vs. 21.9% low, 46.3 vs. 43.5% intermediate and 21.9 vs. 34.6% high risk, p<0.001). Overall, 93.2% of RP patients were enrolled by Urologists and 82.7% of RT patients by Radiation Oncologists. RP patients had generally higher means values of HRQoL items. In MLR models, higher RT rates were independently associated with more advanced age (odds ratio [OR] 6.14, p<0.001) and BMI ≥30 kg/m2 (OR 1.78, p<0.001). Conversely, lower rates of RT were independently associated with married (OR 0.55, p=0.01) and worker status (OR 0.52, p=0.004), enrollment in academic centers (OR 0.59, p=0.005) and higher physical composite score (OR 0.88, p=0.03) and baseline sexual function (OR 0.92, p<0.001) items. CONCLUSIONS: Most patients with clinically localized prostate cancer undergoing definitive treatment at Italian institutions receive RP instead of RT. Moreover, those who are younger, married, working, as well as those with better physical and sexual function are more likely to undergo surgery.

19.
Virchows Arch ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31950242

RESUMO

We report on the clinicopathologic features of 115 cases of high-grade urothelial carcinoma of the upper urinary tract with variant histology present in 39 (34%). Variant histology was typically seen in high pathological stage (pT2-pT4) (82%, 32 cases) patients with lower survival rate (70%, 27 cases, median survival 31 months) and consisted in urothelial with one (23%), two (3%), and three or more variants (3%); 4% of cases presented with pure variant histology. Squamous divergent differentiation was the most common variant (7%) followed by sarcomatoid (6%) and glandular (4%), followed by 3% each of micropapillary, diffuse-plasmacytoid, inverted growth, clear cell glycogenic, or lipid-rich. The pseudo-angiosarcomatous variant is seen in 2%, and 1% each of nested, giant-cell, lymphoepithelioma-like, small-cell, trophoblastic, rhabdoid, microcystic, lymphoid-rich stroma, or myxoid stroma/chordoid completed the study series. Loss of mismatch repair protein expression was identified in one case of upper urinary tract carcinoma with inverted growth variant (3.6%). Variant histology was associated to pathological stage (p = 0.007) and survival status (p = 0.039). The univariate survival analysis identified variant histology as a feature of lower recurrence-free survival (p = 0.046). Our findings suggest that variant histology is a feature of aggressiveness in urothelial carcinoma of the upper urinary tract worth it to be reported.

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