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PURPOSE OF REVIEW: Oligometastatic (om) cancer is considered as a transitional state in between locally confined disease and widespread metastases, accessible to a multimodal treatment, combining systemic and local therapy. In urothelial bladder cancer (BCa), the definitions and the approaches to this condition are poorly standardised and mainly based on retrospective data. We aim to portray the framework for uro-oncologic terminology in omBCa and go through the latest evidence and the future perspectives. RECENT FINDINGS: Retrospective and registry data support the potential benefits of multimodality treatment for carefully selected omBCa patients, especially following a good response to systemic treatment. In 2023, a Delphi consensus has defined omBCa, allowing maximum three metastatic lesions, theoretically amenable to radical local treatment. In de-novo omBCa, surgical treatment of primary tumour might improve overall survival (OS), according to a matched registry analysis; also, consolidative radiotherapy was associated with better OS in two recent cohorts. Furthermore, metastasis-directed therapy (MDT) has shown high local control rates and promising OS (14.9-51âmonths) in a meta-analysis; benefits might be more pronounced for single-site omBCa and nodal or lung lesions. SUMMARY: From a clinical perspective, in de-novo omBCa, the local treatment of primary and metastatic sites might improve disease control and survival, in selected patients; in the oligorecurrent setting, MDT achieves good local symptom control with limited side effects; in selected cases, it could convey a survival benefit, too. From a research perspective, well designed prospective evidence is eagerly awaited, based on recently adopted shared definitions for omBCa.
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Neoplasias de la Vejiga Urinaria , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
INTRODUCTION: The preservation of the bladder neck during robot-assisted radical prostatectomy (RARP) could improve urinary continence recovery and limit the risk of positive surgical margins (PSMs). We refined our lateral approach to the bladder neck technique and compared its outcomes with those of the standard anterior approach. MATERIAL AND METHODS: From a retrospective analysis of 599 consecutive RARPs, 171 patients treated with the lateral and 171 patients treated with the anterior approach were pair-matched 1:1 on the basis of age, grade, and pathological stage. We described our surgical technique and compared the two approaches in terms of basal PSMs, recovery of urinary continence, and complications. RESULTS: As compared to the anterior approach, the lateral approach had shorter operative times and comparable rates of basal PSMs and postoperative complications. The rates of urinary continence after one, three, and 12 months were comparable between the two groups and were generally higher in localized disease. At regression analysis, predictors of urinary incontinence were only age, pathological stage T3b, ISUP grade 5 and nerve-sparing surgery. CONCLUSIONS: The lateral approach leads to an anatomical dissection of the bladder neck without increasing the risk of PSMs. However, no significant benefits in terms of continence recovery were demonstrated over the standard anterior approach.
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INTRODUCTION: When performing targeted biopsy (TBx), the need to add systematic biopsies (SBx) is often debated. Aim of the study is to evaluate the added value of SBx in addition to TBx in terms of prostate cancer (PCa) detection rates (CDR), and to test the concordance between multiparametric magnetic resonance imaging (mpMRI) findings and fusion biopsy results in terms of cancer location. METHODS: We performed a retrospective, multicentric study that gathered data on 1992 consecutive patients who underwent elastic fusion biopsy between 2011 and 2020. A standardized approach was used, with TBx (2-4 cores per target) followed by SBx (12-14 cores). We assessed CDR of TBx, of SBx, and TBx+SBx for all cancers and clinically significant PCa (csPCa), defined as ISUP score ≥2. CDR was evaluated according to radiological and clinical parameters, with a particular focus on PI-RADS 3 lesions. In a subgroup of 1254 patients we tested the discordance between mpMRI findings and fusion biopsy results in terms of cancer location. Uni- and multivariable logistic regression analyses were performed to identify predictors of CDR. RESULTS: CDR of TBx+SBx was 63.0% for all cancers and 38.8% of csPCa. Per-patient analysis showed that SBx in addition to TBx improved CDR by 4.5% for all cancers and 3.4% for csPCa. Patients with lesions scored as PI-RADS 3, 4, and 5 were diagnosed with PCa in 27.9%, 72.8%, and 92.3%, and csPCa in 10.7%, 43.6%, and 69.3%, respectively. When positive, PI-RADS 3 lesions were ISUP grade 1 in 61.1% of cases. Per-lesion analysis showed that discordance between mpMRI and biopsy was found in 56.6% of cases, with 710 patients having positive SBx outside mpMRI targets, of which 414 (58.0%) were clinically significant. PSA density ≥0.15 was a strong predictor of CDR. CONCLUSIONS: The addition of systematic mapping to TBx contributes to a minority of per-patient diagnoses but detects a high number of PCa foci outside mpMRI targets, increasing biopsy accuracy for the assessment of cancer burden within the prostate. High PSA-density significantly increases the risk of PCa, both in the whole cohort and in PI-RADS 3 cases.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Antígeno Prostático Específico , Imagen por Resonancia Magnética/métodos , Biopsia Guiada por Imagen/métodos , BiopsiaRESUMEN
PURPOSE: To summarize evidence regarding the use of neoadjuvant (NAC) and adjuvant chemotherapy (AC) among patients treated with radical nephroureterectomy (RNU). METHODS: A comprehensive literature search of PubMed (MEDLINE), EMBASE and the Cochrane library was performed to identify any original or review article on the role of perioperative chemotherapy for UTUC patients treated with RNU. RESULTS: With regards to NAC, retrospective studies consistently suggested that it may be associated with better pathological downstaging (pDS) ranging from 10.8 to 80% and complete response (pCR) ranging from 4.3 to 15%, while decreasing the risk of recurrence and death as compared to RNU alone. Even higher pDS ranging from 58 to 75% and pCR ranging from 14 to 38% were observed in single-arm phase II trials. With regards to AC, retrospective studies provided conflicting results although the largest report from the National Cancer Database suggested an overall survival benefit in pT3-T4 and/or pN + patients. In addition, a phase III randomized controlled trial showed that the use of AC was associated with a disease-free survival benefit (HR = 0.45; 95% CI = [0.30-0.68]; p = 0.0001) in pT2-T4 and/or pN + patients with acceptable toxicity profile. This benefit was consistent in all subgroups analyzed. CONCLUSIONS: Perioperative chemotherapy improves oncological outcomes associated with RNU. Given the impact of RNU on renal function, the rational is stronger for the use of NAC which impacts final pathology and potentially prolongs survival. However, the level of evidence is stronger for the use of AC that has been proven to decrease the risk of recurrence after RNU with a potential survival benefit.
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Carcinoma de Células Transicionales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Humanos , Nefroureterectomía/métodos , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/cirugía , Estudios Retrospectivos , Quimioterapia Adyuvante/métodos , Neoplasias Ureterales/tratamiento farmacológico , Neoplasias Ureterales/cirugía , Neoplasias Ureterales/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer. STUDY DESIGN AND ENDPOINTS: Against this backdrop, we are running a multi-centre single-arm phase 2 trial of neoadjuvant Durvalumab, a monoclonal antibody targeting programmed cell death ligand 1, combined with Gemcitabine and Cisplatin or Carboplatin for high-risk UTUC patients. The primary outcome is pathological complete response rate at RNU. Secondary endpoints include the partial pathological response rate, safety, as well as disease-free and overall survival. A biomarker analysis is also planned. PATIENTS AND INTERVENTIONS: Included patients must have a good performance status and harbour a non-metastatic UTUC, considered at high risk of progression, defined as either biopsy-proven high-grade disease or invasive features at imaging with or, more recently, without high-grade cytology at the multidisciplinary team discretion, as specified in the latest amendment. Enrolled patients receive 3 cycles of neoadjuvant immuno-chemotherapy before RNU, and the standard of care thereafter. The trial is registered as NCT04617756 and is supervised by an independent data monitoring committee.
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Carcinoma de Células Transicionales , Neoplasias Renales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Humanos , Cisplatino , Carboplatino/uso terapéutico , Gemcitabina , Carcinoma de Células Transicionales/patología , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Ureterales/tratamiento farmacológico , Neoplasias Ureterales/patología , Anticuerpos Monoclonales/uso terapéutico , Pelvis Renal/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
PURPOSE: Transperineal mpMRI-targeted fusion prostate biopsies (TPFBx) are recommended for prostate cancer diagnosis, but little is known about their learning curve (LC), especially when performed under local anaesthesia (LA). We investigated how operators' and institutions' experience might affect biopsy results. METHODS: Baseline, procedure and pathology data of consecutive TPFBx under LA were prospectively collected at two academic Institutions, from Sep 2016 to May 2019. Main inclusion criterion was a positive MRI. Endpoints were biopsy duration, clinically significant prostate cancer detection rate on targeted cores (csCDR-T), complications, pain and urinary function. Data were analysed per-centre and per-operator (with ≥ 50 procedures), comparing groups of consecutive patient, and subsequently through regression and CUSUM analyses. Learning curves were plotted using an adjusted lowess smoothing function. RESULTS: We included 1014 patients, with 27.3% csCDR-T and a median duration was 15 min (IQR 12-18). A LC for biopsy duration was detected, with the steeper phase ending after around 50 procedures, in most operators. No reproducible evidence in favour of an impact of experience on csPCa detection was found at operator's level, whilst a possible gentle LC of limited clinical relevance emerged at Institutional level; complications, pain and IPSS variations were not related to operator experience. CONCLUSION: The implementation of TPFBx under LA was feasible, safe and efficient since early phases with a relatively short learning curve for procedure time.
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Imagen por Resonancia Magnética Intervencional , Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Humanos , Próstata/patología , Curva de Aprendizaje , Anestesia Local , Estudios Prospectivos , Imagen por Resonancia Magnética Intervencional/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , DolorRESUMEN
PURPOSE: To assess differences in referral and pathologic outcomes for uro-oncology cases prior to and during the COVID pandemic, comparing clinical and pathological data of cancer surgeries performed at an academic referral center between 2019 and 2020. METHODS: We collected data of 880 prostate biopsies, 393 robot-assisted radical prostatectomies (RARP) for prostate cancer (PCa), 767 trans-urethral resections of bladder tumor (TURB) and 134 radical cystectomies (RC) for bladder cancer (BCa), 29 radical nephro-ureterectomies (RNU) for upper tract urothelial carcinoma, 130 partial nephrectomies (PN) and 12 radical nephrectomies (RN) for renal cancer, and 41 orchifunicolectomies for testicular cancer. Data of patients treated in 2019 (before COVID-19 pandemic) were compared to patients treated in 2020 (during pandemic). RESULTS: No significant decline in uro-oncological surgical activity was seen between 2019 and 2020. No significant increase in time between diagnosis and surgery was observed for all considered cancers. No differences in terms of main pathologic features were observed in patients undergoing RARP, TURB, RNU, RN/PN, or orchifunicolectomy. A higher proportion of ISUP grade 3 and 4 PCa were diagnosed in 2020 at biopsy (p = 0.001), but this did not translate into worse pathological grade/stage at RARP. In 2020, more advanced disease features were seen after RC, including lymph node involvement (p = 0.01) and non-organ confined disease (p = 0.02). CONCLUSION: Neither decline in uro-oncologic activity nor delay between diagnosis and treatment was observed at our institution during the first year of COVID-19 pandemic. No significant worsening of cancer disease features was found in 2020 except for muscle-invasive BCa.
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COVID-19/epidemiología , Neoplasias de la Próstata/patología , Neoplasias Testiculares/patología , Neoplasias Urológicas/patología , Anciano , Anciano de 80 o más Años , COVID-19/prevención & control , COVID-19/transmisión , Control de Enfermedades Transmisibles , Cistectomía , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Nefroureterectomía , Orquiectomía , Prostatectomía , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/cirugía , Derivación y Consulta , Estudios Retrospectivos , Centros de Atención Terciaria , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/cirugía , Tiempo de Tratamiento , Neoplasias Urológicas/epidemiología , Neoplasias Urológicas/cirugíaRESUMEN
OBJECTIVE: To investigate the diagnostic accuracy of the PI-RADS v2.1 multiparametric magnetic resonance imaging (mpMRI) features in predicting extraprostatic extension (mEPE) of prostate cancer (PCa), as well as to develop and validate a comprehensive mpMRI-derived score (mEPE-score). METHODS: We retrospectively reviewed all consecutive patients admitted to two institutions for radical prostatectomy for PCa with available records of mpMRI performed between January 2015 and December 2020. Data from one institution was used for investigating diagnostic performance of each mEPE feature using radical prostatectomy specimens as benchmark. The results were implemented in a mEPE-score as follows: no mEPE features: 1; capsular abutment: 2; irregular or spiculated margin: 3; bulging prostatic contour, or asymmetry of the neurovascular bundles, or tumor-capsule interface > 1.0 cm: 4; ≥ 2 of the previous three parameters or measurable extraprostatic disease: 5. The performance of mEPE features was evaluated using the five diagnostic parameters and ROC curve analysis. RESULTS: Two-hundred patients were enrolled at site 1 and 76 at site 2. mEPE features had poor sensitivities ranging from 0.08 (0.00-0.15) to 0.71 (0.59-0.83), whereas specificity ranged from 0.68 (0.58-0.79) to 1.00. mEPE-score showed excellent discriminating ability (AUC > 0.8) and sensitivity = 0.82 and specificity = 0.77 with a threshold of 3. mEPE-score had AUC comparable to ESUR-score (p = 0.59 internal validation; p = 0.82 external validation), higher than or comparable to mEPE-grade (p = 0.04 internal validation; p = 0.58 external validation), and higher than early-and-late-EPE (p < 0.0001 internal and external validation). There were no significant differences between readers having different expertise with EPE-score (p = 0.32) or mEPE-grade (p = 0.45), but there were significant differences for ESUR-score (p = 0.02) and early-versus-late-EPE (p = 0.03). CONCLUSIONS: The individual mEPE features have low sensitivity and high specificity. The use of mEPE-score allows for consistent and reliable assessment for pathologic EPE. KEY POINTS: ⢠Individual PI-RADS v2.1 mpMRI features had poor sensitivities ranging from 0.08 (0.00-0.15) to 0.71 (0.59-0.83), whereas Sp ranged from 0.68 (0.58-0.79) to 1.00. ⢠mEPE-score is an all-inclusive score for the assessment of pEPE with excellent discriminating ability (i.e., AUC > 0.8) and Se = 0.82, Sp = 0.77, PPV = 0.74, and NPV = 0.84 with a threshold of 3. ⢠The diagnostic performance of the expert reader and beginner reader with pEPE-score was comparable (p = 0.32).
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Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Proteínas de la Matriz Extracelular , Glicoproteínas , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Clasificación del Tumor , Fosfoproteínas , Prostatectomía/métodos , Neoplasias de la Próstata/patología , Estudios RetrospectivosRESUMEN
OBJECTIVE: To assess the outcomes of multiparametric magnetic resonance imaging (mpMRI) transperineal targeted fusion biopsy (TPFBx) under local anaesthesia. PATIENTS AND METHODS: We prospectively screened 1327 patients with a positive mpMRI undergoing TPFBx (targeted cores and systematic cores) under local anaesthesia, at two tertiary referral institutions, between September 2016 and May 2019, for inclusion in the present study. Primary outcomes were detection of clinically significant prostate cancer (csPCa) defined as (1) International Society of Urological Pathologists (ISUP) grade >1 or ISUP grade 1 with >50% involvement of prostate cancer (PCa) in a single core or in >2 cores (D1) and (2) ISUP grade >1 PCa (D2). Secondary outcomes were: assessment of peri-procedural pain (numerical rating scale [NRS]) and procedure timings; erectile (International Index of Erectile Function) and urinary (International Prostate Symptom Score) function changes; and complications. We also investigated the value of systematic sampling and concordance with radical prostatectomy (RP). RESULTS: A total of 1014 patients were included, of whom csPCa was diagnosed in 39.4% (n = 400). The procedure was tolerable (NRS pain score 3.1 ± 2.3), with no impact on erectile (P = 0.45) or urinary (P = 0.58) function, and a low rate of complications (Clavien-Dindo grades 1 or 2, n = 8; grade >2, n = 0). No post-biopsy sepsis was recorded. Twenty-two men (95% confidence interval [CI] 17-29) needed to undergo additional systematic biopsy to diagnose one csPCa missed by targeted biopsies (D1). ISUP grade concordance of biopsies with RP was as follows: k = 0.40 (95% CI 0.31-0.49) for targeted cores alone and k = 0.65 (95% CI 0.57-0.72; P < 0.05) overall. CONCLUSIONS: The use of TPFBx under local anaesthesia yielded good csPCa detection and was feasible, quick, well tolerated and safe. Infectious risk was negligible. Addition of systematic to targeted cores may not be needed in all men, although it improves csPCa detection and concordance with RP.
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Anestesia Local , Biopsia con Aguja Gruesa/métodos , Biopsia Guiada por Imagen/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Biopsia con Aguja Gruesa/efectos adversos , Hematuria/etiología , Humanos , Biopsia Guiada por Imagen/efectos adversos , Complicaciones Intraoperatorias/etiología , Masculino , Persona de Mediana Edad , Imágenes de Resonancia Magnética Multiparamétrica , Dolor Postoperatorio/etiología , Erección Peniana , Perineo , Estudios Prospectivos , MicciónRESUMEN
OBJECTIVES: To externally validate the currently available nomograms for predicting lymph node invasion (LNI) in patients with prostate cancer (PCa) and to assess the potential risk of complications of extended pelvic lymph node dissection (ePLND) when using the recommended threshold. METHODS: A total of 14 921 patients, who underwent radical prostatectomy with ePLND at eight European tertiary referral centres, were retrospectively identified. After exclusion of patients with incomplete biopsy or pathological data, 12 009 were included. Of these, 609 had undergone multiparametic magnetic resonance imaging-targeted biopsies. Among ePLND-related complications we included lymphocele, lymphoedema, haemorrhage, infection and sepsis. The performances of the Memorial Sloan Kettering Cancer Centre (MSKCC), Briganti 2012, Briganti 2017, Briganti 2019, Partin 2016 and Yale models were evaluated using receiver-operating characteristic curve analysis (area under the curve [AUC]), calibration plots, and decision-curve analysis. RESULTS: Overall, 1158 patients (9.6%) had LNI, with a mean of 17.7 and 3.2 resected and positive nodes, respectively. No significant differences in AUCs were observed between the MSKCC (0.79), Briganti 2012 (0.79), Partin 2016 (0.78), Yale (0.80), Briganti 2017 (0.81) and Briganti 2019 (0.76) models. A direct comparison of older models showed that better discrimination was achieved with the MSKCC and Briganti 2012 nomograms. A tendency for underestimation was seen for all the older models, whereas the Briganti 2017 and 2019 nomograms tended to overestimate LNI risk. Decision-curve analysis showed a net benefit for all models, with a lower net benefit for the Partin 2016 and Briganti 2019 models. ePLND-related complications were experienced by 1027 patients (8.9%), and 12.6% of patients with pN1 disease. CONCLUSIONS: The currently available nomograms have similar performances and limitations in the prediction of LNI. Miscalibration was present, however, for all nomograms showing a net benefit. In patients with only systematic biopsy, the MSKCC and Briganti 2012 nomograms were superior in the prediction of LNI.
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Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Nomogramas , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Anciano , Área Bajo la Curva , Hemorragia/etiología , Humanos , Escisión del Ganglio Linfático/efectos adversos , Linfedema/etiología , Linfocele/etiología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pelvis , Prostatectomía , Curva ROC , Estudios Retrospectivos , Sepsis/etiologíaRESUMEN
OBJECTIVES: To build a machine learning (ML) model to detect extraprostatic extension (EPE) of prostate cancer (PCa), based on radiomics features extracted from prostate MRI index lesions. METHODS: Consecutive MRI exams of patients undergoing radical prostatectomy for PCa were retrospectively collected from three institutions. Axial T2-weighted and apparent diffusion coefficient map images were annotated to obtain index lesion volumes of interest for radiomics feature extraction. Data from one institution was used for training, feature selection (using reproducibility, variance and pairwise correlation analyses, and a correlation-based subset evaluator), and tuning of a support vector machine (SVM) algorithm, with stratified 10-fold cross-validation. The model was tested on the two remaining institutions' data and compared with a baseline reference and expert radiologist assessment of EPE. RESULTS: In total, 193 patients were included. From an initial dataset of 2436 features, 2287 were excluded due to either poor stability, low variance, or high collinearity. Among the remaining, 14 features were used to train the ML model, which reached an overall accuracy of 83% in the training set. In the two external test sets, the SVM achieved an accuracy of 79% and 74% respectively, not statistically different from that of the radiologist (81-83%, p = 0.39-1) and outperforming the baseline reference (p = 0.001-0.02). CONCLUSIONS: A ML model solely based on radiomics features demonstrated high accuracy for EPE detection and good generalizability in a multicenter setting. Paired to qualitative EPE assessment, this approach could aid radiologists in this challenging task. KEY POINTS: ⢠Predicting the presence of EPE in prostate cancer patients is a challenging task for radiologists. ⢠A support vector machine algorithm achieved high diagnostic accuracy for EPE detection, with good generalizability when tested on multiple external datasets. ⢠The performance of the algorithm was not significantly different from that of an experienced radiologist.
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Prostatectomía , Neoplasias de la Próstata , Humanos , Aprendizaje Automático , Imagen por Resonancia Magnética , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND: Prostate cancer is the second most common cancer worldwide. Tumor microenvironment is composed of activated fibroblasts, the so called carcinoma-associated fibroblasts (CAFs). They express high levels of α-smooth muscle actin (α-SMA) and type I collagen (COL1), and support proliferation and migration of tumor epithelial cells. Extracorporeal shock waves (ESWs), acoustic waves, are effective in the treatment of hypertrophic scars, due to their ability to modulate fibrosis. Based on this rationale, the study evaluated the effects of ESWs on CAF activation and the influence of ESW-treated CAFs on the growth and migration of epithelial prostatic carcinoma cells. METHODS: Primary cultures of CAFs (n = 10) were prepared from tumors of patients undergoing surgery for high-risk prostate carcinoma. CAFs were treated with ESWs (energy levels: 0.32 mJ/mm2 , 1000 pulses; 0.59 mJ/mm2 , 250 pulses). After treatment, the messenger RNA and protein levels of the stromal activation markers α-SMA and COL1 were determined. Subsequently, two different stabilized cell lines (PC3 and DU145) of androgen-resistant prostate cancer were treated with the conditioned media produced by ESW-treated CAFs. At different times, viability and migration of PC3 and DU145 cells were evaluated. Viability was also assessed by coculture system using CAFs and PC3 or DU145 cells. RESULTS: ESWs reduced gene expression and protein level of α-SMA and COL1 in CAFs. The treatment of PC3 and DU145 with conditioned media of ESW-treated CAFs determined a reduction of their growth and invasive potential. Coculture systems between ESW-treated CAFs and PC3 or DU145 cells confirmed the epithelial cell number reduction. CONCLUSIONS: This in vitro study demonstrates for the first time that ESWs are able to modulate the activation of prostate CAFs in favor of a less "reactive" stroma, with consequent slowing of the growth and migration of prostate cancer epithelial cells. However, only further studies to be performed in vivo will confirm the possibility of using this new therapy in patients with prostate cancer.
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Tratamiento con Ondas de Choque Extracorpóreas/métodos , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Células del Estroma/patología , Actinas/genética , Actinas/metabolismo , Fibroblastos Asociados al Cáncer/patología , Línea Celular Tumoral , Técnicas de Cocultivo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Progresión de la Enfermedad , Humanos , Masculino , Células PC-3 , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células del Estroma/metabolismoRESUMEN
PURPOSE: Several transperineal biopsy series have proven feasibility under local anesthesia. However, there is a lack of large analyses detailing pain outcomes and factors influencing pain. MATERIALS AND METHODS: From 2016 to 2019 we performed a multicenter prospective study in men undergoing multiparametric magnetic resonance imaging-transperineal fusion biopsies (target+systematic cores) under local anesthesia. Primary outcomes were 1) pain scores (assessed through a 0 to 10-point numeric rating scale) and 2) identification of factors associated with severe pain. The secondary outcome was to evaluate pain influence on clinically significant prostate cancer target cores detection. RESULTS: We included 1,008 men undergoing transperineal fusion biopsies under local anesthesia. Mean±SD numeric rating scale pain scores were 3.9±2.1 at local anesthesia administration and 3.1±2.3 when performing biopsies. Pain was not associated with lower clinically significant prostate cancer detection on targeted cores (p=0.23 and p=0.47 depending on clinically significant prostate cancer definition). On multivariate analysis age (OR 0.96, 95% CI 0.94-0.99) and severe anxiety (OR 2.99, 95% CI 1.83-4.89) were a protective and risk factor, respectively, for severe biopsy pain. Procedural time was also associated with an increased risk of experiencing severe biopsy pain (OR 1.04, 95% CI 1.00-1.08). If aiming to test the possible effects of anxiety preventive measures on pain, an anxiety cutoff greater than 6 on a numeric rating scale would decrease to 13% the number of patients being treated while identifying 56% of those experiencing severe pain. CONCLUSIONS: Transperineal fusion biopsies under local anesthesia result in moderate pain. Pain does not influence clinically significant prostate cancer target detection. Patient anxiety predicts pain. A numeric rating scale based anxiety assessment may be used to identify those at higher risk for experiencing severe pain in men undergoing transperineal fusion biopsies.
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Anestesia Local , Ansiedad/epidemiología , Dolor Asociado a Procedimientos Médicos/epidemiología , Neoplasias de la Próstata/diagnóstico , Anciano , Ansiedad/diagnóstico , Ansiedad/etiología , Ansiedad/psicología , Biopsia con Aguja Gruesa/efectos adversos , Biopsia con Aguja Gruesa/métodos , Biopsia con Aguja Gruesa/psicología , Humanos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Biopsia Guiada por Imagen/psicología , Imagen por Resonancia Magnética Intervencional , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Imágenes de Resonancia Magnética Multiparamétrica , Dimensión del Dolor , Dolor Asociado a Procedimientos Médicos/diagnóstico , Dolor Asociado a Procedimientos Médicos/etiología , Dolor Asociado a Procedimientos Médicos/prevención & control , Perineo/cirugía , Estudios Prospectivos , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/patología , Medición de Riesgo/métodos , Factores de Riesgo , Ultrasonografía IntervencionalRESUMEN
OBJECTIVE: To evaluate machine learning-based classifiers in detecting clinically significant prostate cancer (PCa) with Prostate Imaging Reporting and Data System (PI-RADS) score 3 lesions. METHODS: We retrospectively enrolled 346 patients with PI-RADS 3 lesions at two institutions. All patients underwent prostate multiparameter MRI (mpMRI) and transperineal MRI-ultrasonography (MRI-US)-targeted biopsy. We collected data on age, pre-biopsy serum prostate-specific antigen (PSA) level, prostate volume (PV), PSA density (PSAD), the location of suspicious PI-RADS 3 lesions, and histopathology results. Four machine learning-based classifiers-logistic regression, support vector machine, eXtreme Gradient Boosting (XGBoost), and random forest-were trained using datasets from Nanjing Drum Tower Hospital. External validation was carried out using datasets from Molinette Hospital. RESULTS: Among 287 PI-RADS 3 patients, prostate cancer was proven pathologically in 59 (20.6%), and 228 (79.4%) had benign lesions. For 380 PI-RADS 3 lesions, 81 (21.3%) were proven to be PCa and 299 (78.7%) benign. Among four classifiers, the random forest classifier had the best performance in both patient-based and lesion-based datasets, with overall accuracy of 0.713 and 0.860, sensitivity of 0.857 and 0.613, and area under curve (AUC) of 0.771 and 0.832, respectively. In external validation, our best classifiers had an AUC of 0.688 with the best sensitivity (0.870) and specificity (0.500) in the 59 PI-RADS 3 patients in Molinette Hospital dataset. CONCLUSIONS: The machine learning-based random forest classifier provided a reliable probability if a PI-RADS 3 patient was benign. KEY POINTS: ⢠Machine learning-based classifiers could combine the clinical characteristics with accessible information on image report of PI-RADS 3 patient to generate a probability of malignancy. ⢠This probability could assist surgeons to make diagnostic decisions with more confidence and higher efficiency.
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Biopsia Guiada por Imagen/métodos , Aprendizaje Automático , Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Procedimientos Innecesarios , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Árboles de Decisión , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Próstata/diagnóstico por imagen , Antígeno Prostático Específico/sangre , Curva ROC , Radiografía , Reproducibilidad de los Resultados , Estudios Retrospectivos , Máquina de Vectores de Soporte , Ultrasonografía , Estudios de Validación como AsuntoRESUMEN
PURPOSE: Salvage radical prostatectomy (sRP) represents a curative option for prostate cancer (PCa) biochemical recurrence (BCR) after radiation therapy (RT). In this review, we aimed to outline the contemporary results and use of sRP. METHODS: A web search was performed on the Ovid platform using Embase and Medline databases from January 2010 using pre-defined search terms. Web search was implemented by manual search. Oncological and functional outcomes and complications were summarized using standard classification systems, when feasible. RESULTS: sRP is currently underused, being chosen for radio-recurrent PCa treatment in around 1% of the cases. Surgery is complex due to radiation-induced tissue changes making posterior planes and apex dissection particularly challenging. Patient selection is paramount to maximize the oncological benefit. Most series report a BCR-free survival > 60%, mainly at the end of a short- to intermediate-term follow-up. Five-year progression-free survival is nearly 50% and 5-year cancer-specific survival rates are around 90%. Major peri-operative complications, anastomotic leaks and strictures, still more frequent than in a primary RP setting, have been steering towards more acceptable rates in recent years, when compared to historical series. Continence rates are widely variable, often in between 39 and 60%. Potency remains difficult to recover. CONCLUSIONS: sRP represents a curative option with promising short- to medium-term oncological results and acceptable side effects, in high-volume institutions. In appropriately selected patients, the procedure should not be underused due to the fear of poor functional outcomes and/or complications. Prospective studies are needed to assess the long-term outcomes and to further refine patient selection criteria.
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Recurrencia Local de Neoplasia/cirugía , Prostatectomía/métodos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Terapia Recuperativa , Humanos , MasculinoRESUMEN
Prehabilitation programs play a key role in optimizing patient experiences and outcomes after surgery. However, there are few data on robot-assisted radical prostatectomy, and prehabilitation programs may be challenging to launch and maintain over time for every patient. Here we report our 5-yr experience of an on-site prehabilitation program and its impact on patient and hospital outcomes. During the study period, we observed continuous improvements in the same-day discharge rate (from 0% to 26.4%), hospital stay (from 3 to 0.9. d), costs (-63%), days out of hospital within 30 d after surgery in our center, and in comparison to contemporary nationwide data. However, despite these advantages, maintenance and diffusion of this program could be challenging owing to the absence of incentive support and lack of human resources. This led us to develop two free-access mobile apps, available on the app stores for both patients and surgeons, that include checklists, remote monitoring, and multiple educational materials aimed at simplifying the widespread use of optimized perioperative pathways. PATIENT SUMMARY: We found that a prehabilitation program before surgery can help in optimizing patient outcomes after robot-assisted removal of the prostate. We translated this program into a mobile app available for every patient.
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COVID-19 , Aplicaciones Móviles , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Robótica , Masculino , Humanos , Próstata/cirugía , Neoplasias de la Próstata/cirugía , Ejercicio Preoperatorio , Prostatectomía , Brotes de EnfermedadesRESUMEN
Introduction: This study aimed to evaluate the added diagnostic value of systematic biopsies (SBx) after magnetic resonance imaging (MRI)-targeted biopsies (TBx) and the presence of prostate cancer (PCa) outside MRI targets, in a prospective, contemporary, multicentric series of fusion biopsy patients. Methods: We collected data on 962 consecutive patients who underwent fusion biopsy between 2022 and 2024. Prostate cancer was considered clinically significant (csPCa) in the case of grade ≥ 2. Median test and Fisher exact chi-square tests were used. To identify predictors of out-field positivity, univariate and multivariable logistic regression analyses were performed. Results: Prostate cancer and csPCa were detected by TBx only in 56% and 50%, respectively, and by SBx only in 55% and 45%, respectively (p < 0.001). Prostate cancer and csPCa were diagnosed by TBx in 100 (10%) and 82 (8%) SBx-negative cases and by SBx in 86 (9%) and 54 (6%) TBx-negative cases (p < 0.001). Tumors outside MRI targets were found in 213 (33%) cases in the same lobe and 208 (32%) in the contralateral lobe, most of them being csPCa. Predictors of out-field contralateral PCa were positive DRE (HR 1.50, p 0.03), PSA density ≥ 0.15 (HR 2.20, p < 0.001), and PI-RADS score 5 (HR 2.04, p 0.01). Conclusions: Both TBx and SBx identify a non-negligible proportion of csPCa when the other modality is negative. SBx after TBx should always be considered given the risk of missing other csPCa foci within the prostate, especially in patients with positive DRE, PSA density ≥ 0.15, and PIRADS 5 lesions.