p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas With Adverse Prognosis.

Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (P< 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P= 0.001 and 16.3, 95% CI = 1.8-2151.5; P= 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

Real-world study: Impact of multidisciplinary management of apalutamide-associated adverse events in prostate cancer.

OBJECTIVE: To analyse the adverse events (AEs) associated with apalutamide and the impact of a multidisciplinary team (MDT) protocol on its management at a tertiary care hospital in a real-world setting. METHODS: This was an observational, prospective, cohort study based on real-world evidence at the Hospital Clínic de Barcelona. Includes patients diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) or high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC) and who started treatment with apalutamide between May 2019 and March 2023 in a real-world clinical setting. RESULTS: Of the 121 patients treated with apalutamide, 52.1% experienced an AE, 19.8% experienced temporarily interruption or a reduction in the dose of apalutamide, and 13.2% discontinued treatment due to AEs. Without MDT protocol (49 patients), 24.5% of patients had to temporarily interrupt or reduce the dose of apalutamide due to AEs, with a median time from the start of treatment of 10.1 months, and 24.5% discontinued apalutamide due to AEs, with a median time from the start of treatment of 3.1 months. Meanwhile, whit MDT protocol (72 patients), 16.7% of patients had to temporarily interrupt or reduce the dose of apalutamide due to AEs, with a median time from the start of treatment of 1.6 months, and 5.6% discontinued apalutamide due to AEs, with a median time from the start of treatment of 4 months. The risk reduction associated with treatment discontinuation was statistically significant (p-value = 0.003). CONCLUSIONS: This study highlights the importance of MDT management of AEs associated with apalutamide to reduce treatment discontinuation.

Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer.

Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended for patients with muscle-invasive bladder cancer (MIBC). It has been shown that somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and FANCC are correlated with pathological response to NAC in MIBC. The objective of this study was to validate these genomic biomarkers in pretreatment transurethral resection material from an independent retrospective cohort of 165 patients with MIBC who subsequently underwent NAC and radical surgery. Patients with ypT0/Tis/Ta/T1N0 disease after surgery were defined as responders. Somatic deleterious mutations in ERCC2 were found in nine of 68 (13%) evaluable responders and two of 95 (2%) evaluable nonresponders (p = 0.009; FDR = 0.03). No correlation was observed between response and alterations in ERBB2 or in ATM, RB1, or FANCC alone or in combination. In an exploratory analysis, no additional genomic alterations discriminated between responders and nonresponders to NAC. No further associations were identified between the aforementioned biomarkers and pathological complete response (ypT0N0) after surgery. In conclusion, we observed a positive association between deleterious mutations in ERCC2 and pathological response to NAC, but not overall survival or recurrence-free survival. Other previously reported genomic biomarkers were not validated. PATIENT SUMMARY: It is currently unknown which patients will respond to chemotherapy before definitive surgery for bladder cancer. Previous studies described several gene mutations in bladder cancer that correlated with chemotherapy response. This study confirmed that patients with bladder cancer with a mutation in the ERCC2 gene often respond to chemotherapy.

The Effect of Adverse Surgical Margins on the Risk of Biochemical Recurrence after Robotic-Assisted Radical Prostatectomy.

Positive surgical margins (PSM) after radical prostatectomy are associated with a greater risk of biochemical recurrence (BCR). However, not all PSM harbour the same prognosis for recurrence. We aim to determine the impact of different PSM characteristics and their coexistence on the risk of BCR. This retrospective study included 333 patients that underwent robotic-assisted radical prostatectomy for prostate cancer between 2015−2020 at a single institution. The effect of PSM and their adverse characteristics on the risk of BCR was assessed using Cox proportional hazard models. Kaplan−Meier was used to represent BCR-free survival stratified by margin status. With a median follow-up of 34.5 months, patients with PSM had a higher incidence of BCR, higher risk of relapse and lower BCR-free survival than negative margins (p < 0.001). We established as adverse characteristics: PSM length ≥ 3 mm, multifocality and Gleason at margin > 3. PSM ≥ 3 mm or multifocal PSM were associated with an increased risk for BCR compared to favourable margins (HR 3.50; 95% CI 2.05−5.95, p < 0.001 and HR 2.18; 95% CI 1.09−4.37, p = 0.028, respectively). The coexistence of these two adverse features in the PSM also conferred a higher risk for biochemical relapse and lower BCR-free survival. Adverse Gleason in the margin did not confer a higher risk for BCR than non-adverse margins in our models. We concluded that PSM are an independent predictor for BCR and that the presence of adverse characteristics, such as length and focality, and their coexistence in the PSM are associated with a greater risk of recurrence. Nevertheless, subclassifying PSM with adverse features did not enhance the model's predictive performance in our cohort.

Prognostic implication of TERT promoter mutation and circulating tumor cells in muscle-invasive bladder cancer.

PURPOSE: Current clinical prognostic factors are not accurate enough to identify and monitor those muscle-invasive bladder cancer (MIBC) patients at high risk of progression after radical cystectomy (RC). Here, we determined genetic alterations in the tumor and circulating tumor cell (CTC) enumeration to find biomarkers useful for the management of MIBC after RC. METHODS: Thirty-nine MIBC patients undergoing RC were included. Tumoral tissue DNA was analyzed by next generation sequencing. CTCs were isolated from blood collected before RC and one, four and 12 months later. RESULTS: Sixteen (41%) patients progressed in a median time of 8.5 months and 11 (69%) of these patients harbored the TERT c.-124C > T mutation. All progressive patients harboring the TERT c.-124C > T mutation presented a significant increase in CTC number 12 months after RC compared to those without the mutation. Additionally, CTC number at 12 months was identified as an independent prognostic biomarker for tumor progression and cancer specific survival (CSS). Ten (63%) progressive patients showed an increment of CTC number with a median anticipation period of four months compared with imaging techniques. CONCLUSIONS: The TERT c.-124C > T mutation could be considered a biomarker of aggressivity. CTC enumeration is a useful tool for identifying MIBC patients at high risk of progression and CSS after RC and for detecting tumor progression earlier than imaging techniques.

Outcomes after 20 years of experience in minimally invasive living-donor nephrectomy.

INTRODUCTION: The transperitoneal laparoscopic approach is considered the gold standard technique for living kidney donation. Other accepted laparoscopic techniques include the retroperitoneal approach, natural orifice transluminal endoscopic surgery (NOTES)-assisted, laparo-endoscopic single-site surgery (LESS), with excellent results in the donor and graft. Many studies have compared these techniques with open ones. Our objective is to describe our experience and results in minimally invasive living-donor nephrectomies (MILDN): laparoscopic, NOTES-assisted, and LESS since their introduction in March 2002. MATERIALS AND METHODS: We conducted a retrospective observational study of donors undergoing MILDN between March 2002 and March 2020. RESULTS: A total of 714 MILDNs were performed at our centre. All were completed, except for one, because of recipient death. The conventional laparoscopic approach was used in 541 cases (75.88%), NOTES in 116 (16.9%), LESS in 55 (7.7%), and one mini open (0.14%). Two-thirds of the donors were females (478 cases). The mean donor age was 52.87 years (SD 10.93). Six donors (0.8%) were diagnosed beforehand with a small renal mass, which was removed before transplantation in bench surgery. The right kidney was removed in 17.8% of cases. Warm ischaemia time was higher in the NOTES and LESS groups. We had eight conversions. The global intraoperative and postoperative complication rates were 6.8% and 4.9%, respectively. None of the donors developed renal disease during follow-up (mean 3.68 years). Five-year recipient and graft survival rates were 98.8% and 96.8%, respectively. CONCLUSIONS: MILDN techniques are safe for donors and grafts, with low complication.

Development of a nomogram predicting the probability of stone free rate in patients with ureteral stones eligible for semi-rigid primary laser uretero-litothripsy.

PURPOSE: Few tools are available to predict uretero-lithotripsy outcomes in patients with ureteral stones. Aim of our study was to develop a nomogram predicting the probability of stone free rate in patients undergoing semi-rigid uretero-lithotripsy (ULT) for ureteral stones. METHODS: From January 2014 onwards, patients undergoing semi-rigid Ho: YAG laser uretero-lithotripsy for ureteral stones were prospectively enrolled in two centers. Patients were preoperatively evaluated with accurate clinical history, urinalysis and renal function. Non-contrast CT was used to define number, location and length of the stones and eventually the presence of hydronephrosis. A nomogram was generated based on the logistic regression model used to predict ULT success. RESULTS: Overall, 356 patients with mean age of 54 years (IQR 44/65) were enrolled. 285/356 (80%) patients were stone free at 1 month. On multivariate analysis single stone (OR 1.93, 95% CI 1.05-3.53, p = 0.034), stone size (OR 0.92, 95% CI 0.87-0.97, p = 0.005), distal position (OR 2.12, 95% CI 1.29-3.48, p = 0.003) and the absence of hydronephrosis (OR 2.02, 95% CI 1.08-3.78, p = 0.029) were predictors of success and these were used to develop a nomogram. The nomogram based on the model presented good discrimination (area under the curve [AUC]: 0.75), good calibration (Hosmer-Lemeshow test, p > 0.5) and a net benefit in the range of probabilities between 15 and 65%. Internal validation resulted in an AUC of 0.74. CONCLUSIONS: The implementation of our nomogram could better council patients before treatment and could be used to identify patients at risk of failure. External validation is warranted before its clinical implementation.

Clinical and radiological findings for small renal masses under active surveillance.

OBJECTIVE: To analyze the experience performing active surveillance (AS) of small renal masses (SRMs) in our center and to correlate the evolution of SRMs under AS with clinical and radiological findings. METHODS: Patients on AS between January 2012 until May 2020 for SRMs in our center have been included. Growth rate (GR) per year was analyzed and correlated with radiographic features. Patients with growth kinetics higher than 5mm/year during follow up were offered active treatment. RESULTS: 73 patients were included in AS: the mean age was 75.7 years, a mean initial tumour size of 21.2 mm, and a mean growth rate of 2.05 mm/year. Around 60 % had an ASA score of 3. The tumor size did not change over time in 43% of cases; in 4% we noticed a regression in size and in 52% of cases growth during follow-up (38% 1-5mm/year and 14% more than 5 mm/year). Delayed active treatment was indicated in 16 (21%) of cases. Treatment applied was as following: 2 radiofrequency ablations, 6 radical and 8 partial nephrectomies. A weak correlation was found between initial size and growth rate (r = 0.38, P = 0.02). No significant association was detected regarding any of the analyzed radiological findings and GR. With a mean follow up time of 33 months none of the patients presented metastatic progression. CONCLUSION: Active surveillance is a feasible option for management of SRMs in selected patients without jeopardizing oncological safety. In our series, no clinical or radiological characteristics for predicting tumour growth were found.

Laparoendoscopic single-site simultaneous bilateral nephrectomy: first reported case series.

Bilateral renal tumors in patients on dialysis are usually managed with bilateral nephrectomy. With traditional laparoscopy, this procedure requires the insertion of multiple trocars. Laparoendoscopic single-site surgery (LESS) uses a single umbilical incision to insert multiple instruments and is also employed for extraction of specimens. This technique appears especially useful for bilateral nephrectomy, since many access ports can be spared. We describe 5 cases of simultaneous bilateral radical nephrectomies performed at a single academic institution. We had no intraoperative complications and a mean operating time of 155 minutes. Four patients could be resected using this approach; one case was converted to a traditional laparoscopy. One case had a postoperative complication. We believe this technique is feasible, and can be accomplished with acceptable morbidity and ade-quate operative time.

Susceptibility artifacts and PIRADS 3 lesions in prostatic MRI: how often is the dynamic contrast-enhance sequence necessary?

PURPOSE: To assess the need of the dynamic contrast-enhanced (DCE) sequence in addition to T2-weighted imaging (T2-WI) and diffusion-weighted imaging (DWI) for the detection of clinically significant prostate cancer in the presence of artifacts associated with rectal gas (which compromise the diffusion assessment) and/or PIRADS 3 lesions. METHODS: This retrospective study was approved by the institutional review board; informed consent was not required. Patients referred consecutively over a period of 5 months for elevated PSA underwent multiparametric magnetic resonance imaging (mpMRI). mpMRI was performed using a 3T MRI system without an endorectal coil. The MRI findings were reviewed by two radiologists and were scored according to the Prostate Imaging Reporting and Data System version 2.0 (PI-RADSv2). Any discrepancies were resolved by consensus. For statistical purposes, lesions were classified as PIRADS 1-2, PIRADS 3, or PIRADS 4-5. First, all studies were reviewed using a biparametric assessment (T2-WI + DWI), and the presence or absence of susceptibility artifacts was assessed for each prostate. Subsequently, all images were analyzed using the standard multiparametric approach (T2-WI + DWI + DCE). RESULTS: The biparametric evaluation (T2-WI + DWI) showed artifacts (due to the presence of rectal gas or other) in 87 patients (43.5%) and no artifacts in 113 patients (56.5%). In the latter group, 15 patients had peripheral zone (PZ) PIRADS 3 lesions. Thus, a total of 102 patients (51%) had artifacts or PZ PIRADS 3 lesions and therefore required DCE. When evaluating the group of prostates without artifacts, 13.3% of prostates required DCE. A total of 17 (23.9%) PIRADS 4-5 prostate lesions would have not been detected without the use of DCE. CONCLUSION: Biparametric evaluation of the prostate revealed some limitation due to the presence of artifacts or PIRADS 3 PZ lesions. Artifacts were present in almost 44% of our patients, but when the DWI was correctly evaluated, only 13.3% of prostates required DCE.

Differential gene expression profile between progressive and de novo muscle invasive bladder cancer and its prognostic implication.

This study aimed to ascertain gene expression profile differences between progressive muscle-invasive bladder cancer (MIBC) and de novo MIBC, and to identify prognostic biomarkers to improve patients' treatment. Retrospective multicenter study in which 212 MIBC patients who underwent radical cystectomy between 2000 and 2019 were included. Gene expression profiles were determined in 26 samples using Illumina microarrays. The expression levels of 94 genes were studied by quantitative PCR in an independent set of 186 MIBC patients. In a median follow-up of 16 months, 46.7% patients developed tumor progression after cystectomy. In our series, progressive MIBC patients show a worse tumor progression (p = 0.024) and cancer-specific survival (CSS) (p = 0.049) than the de novo group. A total of 480 genes were found to be differently expressed between both groups. Differential expression of 24 out of the 94 selected genes was found in an independent cohort. RBPMC2 and DSC3 were found as independent prognostic biomarkers of tumor progression and CALD1 and LCOR were identified as prognostic biomarkers of CSS between both groups. In conclusion, progressive and de novo MIBC patients show different clinical outcome and gene expression profiles. Gene expression patterns may contribute to predict high-risk of progression to distant metastasis or CSS.

Prognostic classifier for predicting biochemical recurrence in localized prostate cancer patients after radical prostatectomy.

OBJECTIVE: The purpose of the study was to develop an improved classifier for predicting biochemical recurrence (BCR) in clinically localized PCa patients after radical prostatectomy. METHODS AND MATERIALS: Retrospective study including 122 PCa patients who attended our department between 2000 and 2007. Gene expression patterns were analyzed in 21 samples from 7 localized, 6 locally advanced, and 8 metastatic PCa patients using Illumina microarrays. Expression levels of 41 genes were validated by quantitative PCR in 101 independent PCa patients who underwent radical prostatectomy. Logistic regression analysis was used to identify individual predictors of BCR. A risk score for predicting BCR including clinicopathological and gene expression variables was developed. Interaction networks were built by GeneMANIA Cytoscape plugin. RESULTS: A total of 37 patients developed BCR (36.6%) in a median follow-up of 120 months. Expression levels of 7,930 transcripts differed between clinically localized and locally advanced-metastatic PCa groups (FDR < 0.1). We found that expression of ASF1B and MCL1 as well as Gleason score, extracapsular extension, seminal vesicle invasion, and positive margins were independent prognostic factors of BCR. A risk score generated using these variables was able to discriminate between 2 groups of patients with a significantly different probability of BCR (HR 6.24; CI 3.23-12.4, P< 0.01), improving the individual discriminative performance of each of these variables on their own. Direct interactions between the 2 genes of the model were not found. CONCLUSION: Combination of gene expression patterns and clinicopathological variables in a robust, easy-to-use, and reliable classifier may contribute to improve PCa risk stratification.

Urine cytology suspicious for urothelial carcinoma: Prospective follow-up of cases using cytology and urine biomarker-based ancillary techniques.

BACKGROUND: Urine cytology results that are suspicious for urothelial carcinoma (UC) are challenging. The objective of this study was to elucidate the clinical significance of such results in patients who have a negative cystoscopy. METHODS: In this prospective study, 83 patients who had urine cytology that was suspicious of UC and a negative cystoscopy underwent a second cystoscopy and urine evaluation by cytology, UroVysion fluorescence in situ hybridization (FISH) assay, FGFR3 (fibroblast growth factor receptor 3) and TERT (telomerase reverse transcriptase) mutations and an 8-gene expression classifier (GEC). Results from all techniques were compared with patients' clinical outcomes. RESULTS: The presence of tumor was identified in 41% of patients; of these, 82% had tumors identified at their second evaluation (76% high-grade [HG] tumors), and 18% had tumors identified at a later follow-up (50% were HG tumors). After The Paris System for Reporting urinary Cytology (TPS) reclassification, 53 cytology results still had an indeterminate diagnosis (13 were suspicious for HGUC, and 40 had atypical urothelial cells (AUCs)]. Complete results from second evaluations using urine cytology, cytology-TPS, FISH, and GEC were available for 6 cases that were suspicious for HGUC and 34 cases that had AUCs. The sensitivity of these techniques to detect HG tumors in cases that were suspicious for HGUC was 100%, except for cytology-TPS, for which the sensitivity was 50%. The sensitivity of cytology and cytology-TPS to detect HG tumors in cases with AUCs was 33%, whereas the sensitivity of fluorescence in situ hybridization and GEC in these cases was 83% and 75%, respectively, to detect HG tumors at the second evaluation. CONCLUSIONS: The current results indicate the relevant clinical significance of indeterminate urine cytology findings and strongly suggest the use of complementary evaluations by urine biomarker-based, ancillary techniques to elucidate their significance.

Differentiation of Upper Urinary Tract Lesions Using MDCT: Benign Vs Malignant.

RATIONALE AND OBJECTIVES: To evaluate the accuracy of multiple detector computed tomography (MDCT) in differentiating benign and malignant lesions of upper urinary tract (UUT). MATERIALS AND METHODS: Fifty-four patients with 55 suspected UUT lesions were included in the study. All patients underwent MDCT scan with nephrographic and excretory phases. The unenhanced phase was also performed in 38 cases. The final diagnosis was made by histology in 48 lesions: 43-after surgery, 5-after biopsy and by MDCT follow-up over at least 15 months in the remaining 7 lesions. The following CT features were evaluated: number of lesions, lesion appearance (mass or wall thickening), presence of calcifications, internal border appearance (smooth or irregular), and size and enhancement (presence or absence). The relationship between imaging characteristics and pathology (benign vs malignant) was assessed with logistic regression, univariable diagnostic accuracy, and with classification and regression tree analysis. RESULTS: Patients with mass morphology had a significantly higher probability of malignancy (odds ratio [OR]: 3.73, 95%CI: 1.02-13.72, p = 0.047) compared to patients with thickened wall morphology. The presence of an irregular internal border was also significantly associated with malignancy (OR: 12.14, 95%CI: 2.95-50.06, p < 0.001). No significant associations were found between malignancy and lesion size (p = 0.29), calcifications (p = 0.93) or enhancement (p = 0.68). CONCLUSION: Mass morphology and irregular internal border are reliable signs to suggest malignancy in UUT lesions.

Comparison of standard vs. palliative management for bladder cancer in patients older than 85 years: multicenter study of 317 de novo tumors.

BACKGROUND: The peak incidence of bladder cancer (BCa) occurs at 85 years but data on treatment and outcome are sparse in this age group. We aimed to compare the outcomes of high-grade nonmuscle invasive BCa (HG NMIBC) and muscle invasive BCa (MIBC) treated with standard therapies vs. palliative management in patients >85 years. METHODS: Retrospective multicenter study of 317 patients >85 years who underwent transurethral resection (TURB) for de novo BCa between 2014 and 2016. Standard management consisted in following EAU-guidelines and palliative in monitoring patients without applying oncological treatments after TURB. Low-grade tumors were not compared because all of them were considered to have followed a standard management. RESULTS: Median age was 87 years (85-97). ASA-score was as follows: II, 34.7%; III, 52.1%; IV, 13.2%. Pathological examination showed: 86 Low-grade NMIBC (27.1%), 156 HG NMIBC (49.2%), and 75 MIBC (23.7%). Median follow-up of the series was 21 months (3-61) and median overall survival (OS) 29 (24-33). Among HG NMIBC, 77 patients (49.4%) received standard treatments (BCG, restaging TURB) and 79 (50.6%) palliative management. Among MIBC, 24 (32%) received standard management (cystectomy, radiotherapy, chemotherapy) and 51 (68%) palliative. Applying standard management in HG NMIBC was an independent prognostic factor of OS (44 months vs. 24, HR 1.95; P = 0.013) and decreased the emergency visit rate (33% vs. 43%). In MIBC, the type of management was not a related to OS (P = 0.439) and did not decrease the emergency visit rate (33% vs. 33%). ASA and Charlson-score were not predictors of OS in HG NMIBC (P = 0.368, P = 0.386) and MIBC (P = 0.511, P = 0.665). CONCLUSIONS: Chronological age should not be a contraindication for applying standard therapies in NMIBC. In MIBC the survival is low regardless of the type of management. The lack of correlation between OS and ASA or Charlson-score raises the necessity of a geriatric assessment for selecting the best treatment strategy.

Role of the three-dimensional printing technology incomplex laparoscopic renal surgery: a renal tumor in a horseshoe kidney.

PURPOSE: To report our initial experience using a patient-specific 3D-printed renal tumor model for the surgical planning of a complex heminephrectomy in a horseshoe kidney. MATERIALS AND METHODS: We selected a clinical case for a complex laparoscopic surgery consisting in a 53 year-old male presenting a local recurrence of a renal tumor in a horseshoe kidney with aberrant vascularisation previously treated with a laparoscopic partial nephrectomy. He is now proposed for a laparoscopic left heminephrectomy. Along with conventional imaging, a real-size 3D-printed renal model was used to plan de surgical approach. The perioperative experience of the surgical team was recorded. RESULTS: The surgical team found the patient-specifi c 3D printed model useful for a better understanding of the anatomy and an easier surgical planning. CONCLUSION: The use of patient-specifi c 3D-printed renal models seem to be helpful for the surgical planning in complex renal tumors.

Role of the three-dimensional printing technology in complex laparoscopic renal surgery: a renal tumor in a horseshoe kidney

ABSTRACT Purpose: To report our initial experience using a patient-specific 3D-printed renal tumor model for the surgical planning of a complex heminephrectomy in a horseshoe kidney. Materials and Methods: We selected a clinical case for a complex laparoscopic surgery consisting in a 53 year-old male presenting a local recurrence of a renal tumor in a horseshoe kidney with aberrant vascularisation previously treated with a laparoscopic partial nephrectomy. He is now proposed for a laparoscopic left heminephrectomy. Along with conventional imaging, a real-size 3D-printed renal model was used to plan de surgical approach. The perioperative experience of the surgical team was recorded. Results: The surgical team found the patient-specific 3D printed model useful for a better understanding of the anatomy and an easier surgical planning. Conclusion: The use of patient-specific 3D-printed renal models seem to be helpful for the surgical planning in complex renal tumors.

The influence of treatment sequence in the prognostic value of TMPRSS2-ERG as biomarker of taxane resistance in castration-resistant prostate cancer.

TMPRSS2-ERG expression in blood has been correlated with low docetaxel benefit in metastatic castration-resistant prostate cancer (mCRPC). This multicenter study aimed to prospectively asses its role as a taxane-resistance biomarker in blood and retrospectively in tumors, exploring also the impact of prior abiraterone/enzalutamide (A/E) in patients and in vitro. TMPRSS2-ERG was tested by quantitative reverse-transcription PCR. We included 204 patients (137 blood and 124 tumor samples) treated with taxanes. TMPRSS2-ERG expression was correlated with prostate-specific antigen (PSA)-progression-free survival (PFS), radiological-PFS (RX-PFS), and overall survival (OS). Independent association with survival was evaluated by multivariate Cox modeling. In vitro ERG knockdown and combinatorial and sequential experiments with enzalutamide and docetaxel were performed in VCaP cells. Prior A/E (HR 1.8, 95% CI 1.2-2.8) and blood TMPRSS2-ERG detection (HR 2, 95% CI 1.1-3.7) were independently associated to lower PSA-PFS. In patients without prior A/E, blood and tumor TMPRSS2-ERG independently predicted lower PSA-PFS (HR 3.3, 95% CI 1.4-7.9 and HR 1.8, 95% CI 1.02-3.3, respectively) to taxanes. When prior A/E was administered, TMPRSS2-ERG was not associated with outcome. There was a significant interaction between blood TMPRSS2-ERG and prior A/E related to PSA-PFS (p = 0.032) and RX-PFS (p = 0.009). In vitro stable ERG inhibition did not sensitize VCaP cells to docetaxel. Concomitant enzalutamide and taxanes were synergistic, but prior enzalutamide reduced docetaxel cytotoxicity in VCaP cells. Enzalutamide induced the expression of neuroendocrine markers and reduced that of E-cadherin. We conclude that prior hormone-therapy may influence taxanes response and TMPRSS2-ERG prognostic value. Thus, multiple and sequential biomarkers are needed in CRPC follow-up evaluation.

Mobile phone apps for the prediction of prostate cancer: External validation of the Coral and Rotterdam apps.

OBJECTIVE: To analyze the performance of two mobile phone apps-the Rotterdam prostate cancer risk app and the Coral app-in a cohort of patients undergoing prostate biopsies. METHODS: A consecutive series of men undergoing prostate biopsies were enrolled in two centers. Indications for prostate biopsy included abnormal prostate-specific antigen levels (PSA >4 ng/mL) and/or an abnormal digital rectal examination (DRE). Prostate cancer risk and high-grade prostate cancer risk were assessed using the Rotterdam prostate cancer risk app (iOS) and the Coral app (iOS). The usability of the apps was also assessed and compared using the Post-Study System Usability Questionnaire (PSSUQ) developed by IBM. RESULTS: Overall, 1682 patients with a median age of 68 (62-73) years were enrolled. The Rotterdam app outperformed the Coral app in the prediction of prostate cancer (AUC: 0.70 versus 0.631, p = 0.001) and of high-grade prostate cancer (0.75 versus 0.69, p = 0.001) (Fig. 1). PSSUQ data revealed that both Rotterdam and Coral applications were comparable in terms of usefulness (87% versus 83%, p = 0.708), information quality (74% versus 72%, p = 0.349), interface quality (79% versus 74%, p = 0.216) and satisfaction (76% versus 76%, p = 0.935), respectively. In terms of preferences, 26/50 (54%) preferred the Rotterdam app, while 24/50 (46%) preferred the Coral app. CONCLUSION: In our experience the Rotterdam App outperformed the Coral App for the prediction of prostate cancer or high-grade cancer diagnosis. In particular we confirmed, using the Rotterdam app, that only one out of ten patients with a low Rotterdam score will harbor high-grade prostate cancer on biopsy.