Patient's self-reported quality of life as a prognostic factor in metastatic renal cell carcinoma initially treated with TKI: nomogram proposal.

BACKGROUND: Numerous prognostic factors have been described for metastatic renal cell carcinoma (mRCC). There are nomograms to assist in clinical decision-making and inform patients of their disease progression. However, they have a limited capacity and moderate concordance rates. Performance status (PS) is one of the most widely used prognostic factors and most closely related to overall survival (OS), but this is a subjective assessment based solely on the clinician's opinion. Patients must be at the center of care. Patient-reported outcomes (PROs) have shown benefits but are not widespread in daily clinical practice. METHODS: We analyzed 78 consecutive patients diagnosed with mRCC who initiated treatment at our institution between September 2012 and September 2019. We performed a descriptive analysis of the sample's baseline characteristics and the NCCN FKSI 19 questionnaire. We also conducted a survival analysis. RESULTS: The baseline FKSI 19 score demonstrates its prognostic potential, HR of 0.94 (95% CI 0.92-0.97). Our prognostic model would include: FKSI < 58 (HR 3.61 95% CI 1.97-6.61), anemia, thrombocytosis, non-clear cell histology, and metastatic hepatic involvement. AUC 0.86 (95%CI 0.77-0.95). CONCLUSION: Although it would need external validation, the proposed nomogram could be an alternative to other previously described models. The NCCN FKSI 19 baseline score could replace the clinician's subjective determination of PS. CLINICAL TRIAL REGISTRATION: Not applicable.

Prospective study of diagnostic accuracy in the detection of high-grade prostate cancer in biopsy-naïve patients with clinical suspicion of prostate cancer who underwent the Select MDx test.

OBJECTIVES: This study aimed to externally validate the diagnostic accuracy of the Select MDx test for Significant prostate cancer (Sig PCa) (ISUP > 1), in a contemporaneous, prospective, multicenter cohort with a prostate-specific antigen (PSA) between 3 and 10 ng/ml and a non-suspicious digital rectal examination. METHODS AND PARTICIPANTS: For all enrolled patients, the Select Mdx test, the risk calculator ERSPC3 + DRE, and a prostatic magnetic resonance imaging (MRI) were carried out. Subsequently, a systematic 12-core trans-rectal biopsy and a targeted biopsy, in the case of a prostate imaging-reporting and data system (PIRADS) > 2 lesion (max three lesions), were performed. To assess the accuracy of the Select MDx test in the detection of clinically Sig PCa, the test sensitivity was evaluated. Secondary objectives were specificity, negative predictive value (NPV), positive predictive value (PPV), and area under the curve (AUC). A direct comparison with the ERSPC + DRE risk calculator and MRI were also performed. We also studied the predictive ability to diagnose Sig PCa from the combination of the Select MDx test with MRI using clinical decision-curve analysis. RESULTS: There were 163 patients enrolled after meeting the inclusion criteria and study protocol. The Select MDx test showed a sensitivity of 76.9% (95% CI, 63.2-87.5), 49.6% specificity (95% CI, 39.9-59.2), 82.09% (95% CI, 70.8-90.4) NPV, and 41.67% (95% CI, 31.7-52.2) PPV for the diagnosis of Sig PCa. COR analysis was also performed, which showed an AUC of 0.63 (95% CI, 0.56-0.71). There were no differences in the accuracy of Select MDx, ERSPC + DRE, or MRI. The combination of Select MDX + MRI showed the highest impact in the decision-curve analysis, with an NPV of 93%. CONCLUSION: Our study showed a worse performance for the SelectMdx test than previously reported, within a cohort of patients with a PSA 3-10 ng/ml and a normal DRE, with results similar to those from ERSPC + DRE RC and MRI, but with an improvement in the usual PSA pathway. A combination of the Select Mdx test and MRI could improve accuracy, but studies specifically evaluating this scenario with a cost-effective analysis are needed.

Outcomes and Safety of Biweekly and Monthly Nivolumab in Patients with Metastatic Renal Cell Carcinoma and Dialysis: Three Case Reports and Literature Review.

Nivolumab is a fully human immunoglobulin G4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody that selectively blocks the interaction between PD-1, which is expressed on activated T cells, and its ligands PD-L1 and PD-L2, which are expressed on immune cells and tumour cells. Patients with severe renal dysfunction and haemodialysis are not enrolled in clinical trials. However, in daily clinical practice, we have patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease (ESRD). The scientific evidence about the efficacy and safety of nivolumab in these patients is scarce. We report three cases of mRCC patients with ESRD treated with second-line nivolumab therapy. They received both biweekly and monthly schemes. None of our patients showed grade 2-4 toxicities. Two patients achieved partial response and one progressive disease as best response. Our patients did not show increased toxicity by ESRD; also, two of the three patients had objectifiable clinical benefit. Nivolumab seems to be similarly safe for ESRD or dialysis patients as for patients without impaired kidney function (IKF). Dose adjustments might not be necessary. We suggest that patients on dialysis could be treated with nivolumab in the same way as populations without IKF.

Prediction of Clinically Significant Prostate Cancer by a Specific Collagen-related Transcriptome, Proteome, and Urinome Signature.

BACKGROUND AND OBJECTIVE: While collagen density has been associated with poor outcomes in various cancers, its role in prostate cancer (PCa) remains elusive. Our aim was to analyze collagen-related transcriptomic, proteomic, and urinome alterations in the context of detection of clinically significant PCa (csPCa, International Society of Urological Pathology [ISUP] grade group ≥2). METHODS: Comprehensive analyses for PCa transcriptome (n = 1393), proteome (n = 104), and urinome (n = 923) data sets focused on 55 collagen-related genes. Investigation of the cellular source of collagen-related transcripts via single-cell RNA sequencing was conducted. Statistical evaluations, clustering, and machine learning models were used for data analysis to identify csPCa signatures. KEY FINDINGS AND LIMITATIONS: Differential expression of 30 of 55 collagen-related genes and 34 proteins was confirmed in csPCa in comparison to benign prostate tissue or ISUP 1 cancer. A collagen-high cancer cluster exhibited distinct cellular and molecular characteristics, including fibroblast and endothelial cell infiltration, intense extracellular matrix turnover, and enhanced growth factor and inflammatory signaling. Robust collagen-based machine learning models were established to identify csPCa. The models outcompeted prostate-specific antigen (PSA) and age, showing comparable performance to multiparametric magnetic resonance imaging (mpMRI) in predicting csPCa. Of note, the urinome-based collagen model identified four of five csPCa cases among patients with Prostate Imaging-Reporting and Data System (PI-IRADS) 3 lesions, for which the presence of csPCa is considered equivocal. The retrospective character of the study is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: Collagen-related transcriptome, proteome, and urinome signatures exhibited superior accuracy in detecting csPCa in comparison to PSA and age. The collagen signatures, especially in cases of ambiguous lesions on mpMRI, successfully identified csPCa and could potentially reduce unnecessary biopsies. The urinome-based collagen signature represents a promising liquid biopsy tool that requires prospective evaluation to improve the potential of this collagen-based approach to enhance diagnostic precision in PCa for risk stratification and guiding personalized interventions. PATIENT SUMMARY: In our study, collagen-related alterations in tissue, and urine were able to predict the presence of clinically significant prostate cancer at primary diagnosis.

Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy.

Since prostate cancer (PCa) was described as androgen-dependent, the androgen receptor (AR) has become the mainstay of its systemic treatment: androgen deprivation therapy (ADT). Although, through recent years, more potent drugs have been incorporated, this chronic AR signaling inhibition inevitably led the tumor to an incurable phase of castration resistance. However, in the castration-resistant status, PCa cells remain highly dependent on the AR signaling axis, and proof of it is that many men with castration-resistant prostate cancer (CRPC) still respond to newer-generation AR signaling inhibitors (ARSis). Nevertheless, this response is limited in time, and soon, the tumor develops adaptive mechanisms that make it again nonresponsive to these treatments. For this reason, researchers are focused on searching for new alternatives to control these nonresponsive tumors, such as: (1) drugs with a different mechanism of action, (2) combination therapies to boost synergies, and (3) agents or strategies to resensitize tumors to previously addressed targets. Taking advantage of the wide variety of mechanisms that promote persistent or reactivated AR signaling in CRPC, many drugs explore this last interesting behavior. In this article, we will review those strategies and drugs that are able to resensitize cancer cells to previously used treatments through the use of "hinge" treatments with the objective of obtaining an oncological benefit. Some examples are: bipolar androgen therapy (BAT) and drugs such as indomethacin, niclosamide, lapatinib, panobinostat, clomipramine, metformin, and antisense oligonucleotides. All of them have shown, in addition to an inhibitory effect on PCa, the rewarding ability to overcome acquired resistance to antiandrogenic agents in CRPC, resensitizing the tumor cells to previously used ARSis.

[Recurrence and progression after BCG.] / Concepto de recidiva, recurrencia y progresión tras BCG.

BCG is currently the standard of care in intermediate and high risk non-invasive bladder tumors. In high-risk patients treated with BCG up to 30% will recurand 10% will progress within 2 years. Oncological outcomes with bladder preserving strategies are limited so radical cystectomy is recommended after BCG failure. Some promising treatments, such as check point inhibitors (PD1, PDL-1), are being studied for non-responders to BCG. Knowing the management of critical situations during BCG treatment its crucial in daily practice and clinical trials design. The aim of this study is to present these definitions and to remember some important aspect sof BCG management.

La BCG es en la actualidad el tratamiento de elección en tumores vesicales no músculo invasivo de riesgo intermedio y alto. De los pacientes de alto riesgo tratados con BCG, hasta un 30% recidivarán y un 10% progresarán en 2 años. Los resultados oncológicos de estos pacientes con estrategias de conservación vesical son modestos, por lo que la cistectomía radicales el tratamiento de elección tras fallo de BCG. Están siendo estudiadas diferentes opciones de tratamiento para pacientes no respondedores a BCG, como son los inhibidores de los puntos de control (PD1, PDL-1). Para el diseño de los ensayos clínicos (EC) y para homogeneizar nuestra práctica clínica diaria, es necesario tener clara la definición de una serie de situaciones, en las que nos podemos encontrar durante un tratamiento con BCG. El objetivo de este trabajo es revisar estas definiciones y recordar algunos aspectos del manejo de la BCG implicados en las mismas.

[Analysis of the quality of the information on the erectile dysfunction in YouTube.] / Análisis de la calidad de la información sobre disfunción eréctil en YouTube.

OBJECTIVE: The objective of our study is to stablish the scientific quality of the available information in YouTube about erectile dysfunction (ED). MATERIAL AND METHODS: We searched on YouTube thrree terms ("Problemas de Erección" (PE), "Impotencia"(I) y "Disfunción Eréctil" (DE)). The sixteen first videos from each term were selected for the analysis. Two independent urologists reviewed all videos and classified all of them in scientific evidence-based (SEB) or not scientific evidence-based (NSEB) according to the current literature. In the subgroup analysis we compare: number of visits, duration, time of publication, source and type of information. RESULTS: After excluding the repeated links and non-concordant videos between both urologists, we analysed 147 videos. The Kappa statistic was 0.89 (95% CI0.85-0.96). 37% were considered SEB and 63% were considered NSEB. The median of reproductions in the SEB group was 24.356 (96-126.410) and 44.416 for NSEB (190-10.318.642); this difference was statistically significant. The median duration was 254 seconds(46-984) for the SEB group and 228 seconds for the NSEB (23-2.880); the median time of publication was 42 (16-103) months for the SEB group and 29 (11-134) months for the other one. 83% of SEB videos were published in health networks and television programs,while 58% of NSEB were published in user blogs. The SEB videos show more information about pathophysiology,aetiology, endothelial dysfunction, diagnosis and treatment than NSEB (p<0.001). CONCLUSIONS: 37% of the videos were consideredSEB. The NSEB videos were significantly more playedthan SEB group.

OBJETIVO: Nuestro objetivo es analizar la calidad de la información disponible en YouTube acerca de la disfunción eréctil.MATERIAL Y MÉTODOS: Realizamos una búsqueda en YouTube usando los términos "Problemas de Erección" (PE), "Impotencia" (I) y "Disfunción Eréctil" (DE); incluimos los 60 primeros vídeos para cada uno de ellos. Dos urólogos revisaron de forma independiente los videos clasificándolos en "Basados en evidenciacientífica" (BEC) y "No basados en evidencia científica" (NBEC) según la bibliografía actual. Se describen y comparan el número de visitas, la duración, el tiempo publicado, la información médica y el origen de cada vídeo por grupos. RESULTADOS: Analizamos 147 videos tras eliminar los repetidos y no concordantes. El índice Kappa fue 0,89 (IC95% 0,82-0,96). El 37% se consideraron BEC y el 63% NBEC. La mediana de reproducciones en el grupo BEC fue 24.356 (rango 96-126.410) y 44.416 entre los NBEC (190-10.318.642), siendo esta diferencia estadísticamente significativa. La mediana de duración fue 254 segundos (46-984) y 228 segundos(23-2.880) respectivamente; la mediana de tiempo publicado fue de 42 meses en los BEC (16-103) y de 29 en los NBEC (11-134). El 83% de los vídeos BEC provenían de webs de salud y programas de televisión,mientras que el 58% de los NBEC procedían de blogs.Los vídeos BEC trataban más de fisiopatología, etiología,disfunción endotelial, diagnóstico y tratamiento frente a los NBEC (p<0,001).CONCLUSIÓN: Del total de videos revisados, el 37% se consideraron BEC. Los videos NBEC se reprodujeron más veces que los BEC.