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BACKGROUND: The extent of pelvic lymphadenectomy (PLND) as part of radical cystectomy (RC) for bladder cancer (BC) remains unclear. Sentinel-based and lymphangiographic approaches could lead to reduced morbidity without sacrificing oncologic safety. OBJECTIVE: To evaluate the feasibility and diagnostic value of fluorescence-guided template sentinel region dissection (FTD) using a handheld near-infrared fluorescence (NIRF) camera in open radical cystectomy. DESIGN, SETTING, AND PARTICIPANTS: After peritumoral cystoscopic injection of indocyanine green (ICG) 21 patients underwent open RC with FTD due to BC between June 2019 and June 2021. Intraoperatively, the FIS-00 Hamamatsu Photonics® NIRF camera was used to identify and resect fluorescent template sentinel regions (FTRs) followed by extended pelvic lymphadenectomy (ePLND) as oncological back-up. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: Descriptive analysis of positive and negative results per template region. RESULTS AND LIMITATIONS: FTRs were identified in all 21 cases. Median time (range) from ICG injection to fluorescence detection was 75 (55-125) minutes. On average (SD), 33.4 (9.6) lymph nodes were dissected per patient. Considering template regions as the basis of analysis, 67 (38.3%) of 175 resected regions were NIRF-positive, with 13 (7.4%) regions harboring lymph node metastases. We found no metastatic lymph nodes in NIRF-negative template regions. Outside the standard template, two NIRF-positive benign nodes were identified. CONCLUSION: The concept of NIRF-guided FTD proved for this group all lymph node metastases to be found in NIRF-positive template regions. Pending validation in a larger collective, resection of approximately 40% of standard regions may be sufficient and may result in less morbidity.
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Cistectomia , Excisão de Linfonodo , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Excisão de Linfonodo/métodos , Excisão de Linfonodo/instrumentação , Cistectomia/métodos , Cistectomia/instrumentação , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Verde de Indocianina , Estudos de Viabilidade , Fluorescência , Prognóstico , Seguimentos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Linfonodos/patologia , Linfonodos/cirurgia , Linfonodos/diagnóstico por imagem , Idoso de 80 Anos ou mais , CorantesRESUMO
Immune-checkpoint-inhibitor (ICI) therapy has been one of the major advances in the treatment of a variety of advanced or metastatic tumors in recent years. Therefore, ICI-therapy is already approved in first-line therapy for multiple tumors, either as monotherapy or as combination therapy. However, there are relevant differences in approval among different tumor entities, especially with respect to PD-L1 testing. Different response to ICI-therapy has been observed in the pivotal trials, so PD-L1 diagnostic testing is used for patient selection. In addition to PD-L1 testing of tumor tissue, liquid biopsy provides a noninvasive way to monitor disease in cancer patients and identify those who would benefit most from ICI-therapy. This overview focuses on the use of ICI-therapy and how it relates to common and potential future biomarkers for patient-directed treatment planning.
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Antineoplásicos Imunológicos , Neoplasias , Oncologistas , Humanos , Antígeno B7-H1 , Patologistas , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Biomarcadores TumoraisRESUMO
PURPOSE: Although active surveillance (AS) is recommended for low- to favorable intermediate-risk prostate cancer (PCa), risk of upgrading at radical prostatectomy (RP) is not negligible. Available studies based on systematic transrectal ultrasound biopsy might not be applicable to contemporary cohorts diagnosed with MRI-targeted biopsy (TB). The aim of the present study is to explore rates and risk factors for adverse outcomes (AO) at RP in patients with ISUP ≤ 2 PCa detected at TB with concomitant systematic biopsy (SB). METHODS: Multicenter, retrospective analysis of 475 consecutive patients with ISUP ≤ 2 PCa at MRI-TB + SB is treated with RP. AO were defined as ISUP upgrading, adverse pathology (upgrading to ISUP ≥ 3 and/or ≥ pT3 at RP, and/or pN1) (AP) or biochemical recurrence (BCR) in men with follow-up (n = 327). RESULTS: The rate of ISUP upgrading, upgrading ≥ 3, and AP were 39%, 21%, and 43%. Compared to ISUP2, men with ISUP1 PCa had a higher rate of overall upgrading (27 vs. 67%, p < 0.001), but less upgrading to ≥ 3 (27 vs. 10%, p < 0.001). AP was more common when ISUP2 was detected with a combined MRI-TB + SB approach compared to considering TB (p = 0.02) or SB (p = 0.01) alone. PSA, PSA density, PI-RADS, ISUP at TB, overall biopsy ISUP and EAU classification were predictors of upgrading to ISUP ≥ 3 and AP. The 1 year BCR-free survival was 94% with no differences in BCR rates between subgroups. CONCLUSION: Upgrading in ISUP ≤ 2 PCa remains prevalent even in men diagnosed in the MRI era. The use of MRI-TB with concomitant SB allows for the accurate identification of ISUP2 PCa and predicts the risk of AO at RP.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética , Antígeno Prostático Específico , Estudos Retrospectivos , Biópsia , Prostatectomia , Gradação de Tumores , Biópsia Guiada por ImagemRESUMO
PURPOSE: To date, over 4.2 million Germans and over 235 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Uro-oncology (UO) patients are particularly vulnerable but in urgent need of life-saving systemic treatments. Our multicentric study examined the impact of the COVID-19 crisis on the medical care of UO patients in German university hospitals receiving ongoing systemic anti-cancer treatment and to detect the delay of medical care, defined as deferred medical treatment or deviation of the pre-defined follow-up assessment. METHODS: Data of 162 UO patients with metastatic disease undergoing systemic cancer treatment at five university hospitals in Germany were included in our analyses. The focus of interest was any delay or change in treatment between February 2020 and May 2020 (first wave of the COVID-19 crisis in Germany). Statistical analysis of contingency tables were performed using Pearson's chi-squared and Fisher's exact tests, respectively. Effect size was determined using Cramér's V (V). RESULTS: Twenty-four of the 162 patients (14.8%) experienced a delay in systemic treatment of more than 2 weeks. Most of these received immuno-oncologic (IO) treatments (13/24, 54.2%, p = 0.746). Blood tests were delayed or canceled significantly more often in IO patients but with a small effect size (21.1%, p = 0.042, V = 0.230). Treatment of patients with renal cell carcinoma (12/73, 16.4%) and urothelial carcinoma (7/32, 21.9%) was affected the most. CONCLUSIONS: Our data show that the COVID-19 pandemic impacted the medical care of UO patients, but deferment remained modest. There was a tendency towards delays in IO and ADT treatments in particular.
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COVID-19 , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , COVID-19/terapia , Hospitais Universitários , Humanos , Pandemias , SARS-CoV-2 , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/terapiaRESUMO
PURPOSE: The extent of variation in urinary and sexual functional outcomes after radical prostatectomy (RPE) between prostate cancer (PC) operating sites remains unknown. Therefore, this analysis aims to compare casemix-adjusted functional outcomes (EPIC-26 scores incontinence, irritative/obstructive function and sexual function) between operating sites 12 months after RPE. MATERIALS AND METHODS: Analysis of a cohort of 7065 men treated with RPE at 88 operating sites (prostate cancer centers, "PCCs") between 2016 and 2019. Patients completed EPIC-26 and sociodemographic information surveys at baseline and 12 months after RPE. Survey data were linked to clinical data. EPIC-26 domain scores at 12 months after RPE were adjusted for relevant confounders (including baseline domain score, clinical and sociodemographic information) using regression analysis. Differences between sites were described using minimal important differences (MIDs) and interquartile ranges (IQR). The effects of casemix adjustment on the score results were described using Cohen's d and MIDs. RESULTS: Adjusted domain scores at 12 months varied between sites, with IQRs of 66-78 (incontinence), 89-92 (irritative/obstructive function), and 20-29 (sexual function). Changes in domain scores after casemix adjustment for sites ≥ 1 MID were noted for the incontinence domain (six sites). Cohen's d ranged between - 0.07 (incontinence) and - 0.2 (sexual function), indicating a small to medium effect of casemix adjustment. CONCLUSIONS: Variation between sites was greatest in the incontinence and sexual function domains for RPE patients. Future research will need to identify the factors contributing to this variation. TRIAL REGISTRY: The study is registered at the German Clinical Trial Registry ( https://www.drks.de/drks_web/ ) with the following ID: DRKS00010774.
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Neoplasias da Próstata , Incontinência Urinária , Sistema Urinário , Humanos , Masculino , Próstata , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Incontinência Urinária/cirurgiaRESUMO
OBJECTIVE: Patients with bladder cancer (BC) are at risk of developing upper tract urothelial carcinoma (UTUC). Therefore, CT urography is recommended for follow-up. To avoid intravenous contrast agents, retrograde pyelography (RPG) is an alternative. However, it is still unclear whether RPG increases the incidence of UTUC. The aim of this study was to investigate the impact of RPG in the presence of BC on the risk of developing UTUC. PATIENTS AND METHODS: Retrospectively analysing a total of 3,680 RPGs between 2009 and 2016, all patients with simultaneous BC (group 1) and those without synchronous BC (group 2) during RPG were compared. All patients were risk stratified according to the EORTC bladder calculator. In patients without BC during RPG, risk stratification was based on the worst prior tumour characteristics. RESULTS: A total of 145 patients with a history of BC were analysed. Of these, 112 patients underwent RPG with simultaneous BC. UTUC developed in 6 of 112 patients (5.4%) and 58.9% (66/112) had high-risk BC according to the EORTC bladder calculator. In the control group, one out of 33 (3%) patients with metachronous high-risk BC developed UTUC. CONCLUSIONS: Using RPG in the presence of BC did not increase the risk of UTUC. Due to the predominant number of high-risk/high-grade tumours, individual tumour biology appears to be the primary driver for the development of UTUC.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Carcinoma de Células de Transição/patologia , Humanos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , UrografiaRESUMO
PURPOSE: To evaluate fibroblast-activation-protein (FAP) expression in different clinical stages of prostate cancer (PC) with regards to utility of [68 Ga]Ga-FAPI-04 PET/CT imaging in patients with castration-resistant PC (CRPC). METHODS: Tissue microarrays (TMAs) were constructed from prostatic tissue from 94 patients at different stages of PC (primary PC, patients undergoing neoadjuvant androgen deprivation therapy, CRPC, and neuroendocrine PC (NEPC)) and were stained with anti-FAP monoclonal antibody. A positive pixel count algorithm (H-Index) was used to compare FAP expression between the groups. Additionally, three men with advanced CRPC or NEPC underwent [68 Ga]Ga-FAPI-04 PET/CT, and PET positivity was analyzed. RESULTS: The mean H-index for benign tissue, primary PC, neoadjuvant androgen deprivation therapy before radical prostatectomy, CRPC, and NEPC was 0.018, 0.031, 0.042, 0.076, and 0.051, respectively, indicating a significant rise in FAP expression with advancement of disease. Corroborating these findings [68 Ga]Ga-FAPI-04 PET/CT was highly positive in men with advanced CRPC. CONCLUSION: Increased FAP tissue expression supports the use of FAP inhibitor (FAPI)-molecular theranostics in CRPC.
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Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios , Fibroblastos , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Medicina de Precisão , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagemRESUMO
In locally or locally advanced solid tumors, surgery still remains a fundamental treatment method. However, conservative resection is associated with high collateral damage and functional limitations of the patient. Furthermore, the presence of residual tumor tissue following conservative surgical treatment is currently a common cause of locally recurrent cancer or of distant metastases. Reliable intraoperative detection of small cancerous tissue would allow surgeons to selectively resect malignant areas: this task can be achieved by means of image-guided surgery, such as beta radioguided surgery (RGS). In this paper, a comprehensive review of beta RGS is given, starting from the physical principles that differentiate beta from gamma radiation, that already has its place in current surgical practice. Also, the recent clinical feasibility of using Cerenkov radiation is discussed. Despite being first proposed several decades ago, only in the last years a remarkable interest in beta RGS has been observed, probably driven by the diffusion of PET radiotracers. Today several different approaches are being pursued to assess the effectiveness of such a technique, including both beta+ and beta- emitting radiopharmaceuticals. Beta RGS shows some peculiarities that can present it as a very promising complementary technique to standard procedures. Good results are being obtained in several tests, both ex vivo and in vivo. This might however be the time to initiate the trials to demonstrate the real clinical value of these technologies with seemingly clear potential.
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Recidiva Local de Neoplasia , Cirurgia Assistida por Computador , Humanos , Compostos RadiofarmacêuticosRESUMO
INTRODUCTION: High baseline YKL-40 serum levels are associated with drug resistance in several solid tumours. However, their role in predicting docetaxel (DOC) resistance in prostate cancer (PCa) is unknown. METHODS: Pre-treatment serum levels of YKL-40 and prostate-specific antigen (PSA) were analyzed in 109 castration-resistant prostate cancer patients who underwent DOC-therapy. Responsive patients were retreated by repeated series of DOC. Results were compared with the clinical parameters as well as overall (OS) and disease-specific survival (DSS). RESULTS: YKL-40 but not PSA serum levels were significantly higher in patients with baseline resistance to DOC (p = 0.035). Higher YKL-40 and PSA levels were detected in patients with bone metastasis (p = 0.032; p = 0.010) and in those who were not pre-treated with radical prostatectomy (p = 0.011, p = 0.008). High YKL-40 levels were associated with shorter OS (p = 0.037) and DSS (p = 0.017) in patients who received DOC in the first-line setting. In multivariable analysis, ECOG performance status (p = 0.009), presence of any metastases (p = 0.016) and high PSA levels (p = 0.005) remained independent predictors for DSS. CONCLUSIONS: YKL-40 may help to identify patients with baseline resistance to DOC and therefore may help to optimize treatment decisions. In accordance, high pre-treatment YKL-40 serum levels were associated with shorter OS and DSS in patients who received DOC as first-line therapy.
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Proteína 1 Semelhante à Quitinase-3/sangue , Docetaxel/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias da Próstata/sangue , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológicoRESUMO
BACKGROUND: To evaluate postoperative pain intensity and length of hospital stay after open or robotic thoracic surgery in a standardized postoperative pain therapy setting. METHODS: In the present retrospective (oberservation period: January 2015 until January 2016) study we matched data of 38 patients with robotic thoracic surgery ("robotic patients"; age: 62.2 years, male gender: 42.1%) with 38 patients with open thoracic surgery ("open patients"; age: 62.5 years, male gender: 42.1%). Power analysis indicated that 36 patients per group would be required. RESULTS: 68% of all patients received an epidural catheter, and 32% a systemic opioid based analgesia. Postoperative pain intensity in "robotic patients" was lower at rest on postoperative day 3-5 compared to "open patients" (NRS POD 3 robotic surgery 0.5±1.0 vs. open surgery 1.0±1.6, p = 0.04; NRS POD 4 robotic surgery 0,5 ± 1.0 vs. open surgery 1.1±1.3, p=0.04; NRS POD 5 robotic surgery 0.7 ± 1.0 vs. open surgery 1.5±1.5, p=0.003). Chest tube duration was shorter in "robotic patients" (2.9 ± 2.0 days vs. 4.9 ± 2.2 days; p < 0.001). Moreover, length of hospital stay was shorter in "robotic patients" than in "open patients" (6.9 days vs. 8.0 days; p = 0.02). There was no significant difference in postoperative opioid consumption between the groups. Nearly 95% of patients were discharged home with an oral opioid in both groups. CONCLUSION: Patients after robotic pulmonary resection experience lower postoperative pain and are discharged earlier from hospital than patients after open thoracic surgery. STUDY LIMITATIONS: The study design is retrospectively.
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Analgesia Epidural , Analgésicos Opioides/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Neoplasias Pulmonares/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Pneumonectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Torácica Vídeoassistida/métodos , Toracotomia/métodos , Idoso , Tubos Torácicos , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Manejo da Dor , Período Pós-Operatório , Estudos Retrospectivos , Toracoscopia/métodosAssuntos
Luminescência , Neoplasias da Próstata , Ácido Edético/análogos & derivados , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Oligopeptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: To assess the clinical efficacy of controlled-release oxycodone for postoperative analgesia after video-assisted thoracic surgery (VATS) or thoracoscopy. METHODS: Pain therapy is standardized in our thoracic center throughout the complete postoperative stay. Patients receive immediately postoperative standardized oral analgesic protocol with controlled-released oxycodone (Oxy Group) or oxycodone with naloxone (Targin Group) and nonopioid every 6 h. We switched the opioid protocol from controlled-release oxycodone to Targin in January 2012. All patients are visited daily by a pain specialist throughout the whole stay. RESULTS: Data of 788 patients undergoing VATS (n = 367) or thoracoscopy (n = 421) during January 2011 until March 2013 were analyzed. In VATS, patients with Targin had higher pain scores at rest (p < 0.02) and on coughing (p < 0.001) than patients with oxycodone alone and more patients with Targin were dismissed with oral opioid dose than patients with oxycodone alone (p < 0.001). No differences in pain scores on POD 5 and 6, or in length of hospital stay, incidence of nausea, time to first dejection or opioid dose after dismission were found between controlled-release oxycodone and Targin. After conventional thoracoscopy, 209 patients received controlled-release oxycodone and 212 Targin. Patients with Targin had higher pain scores at rest (p < 0.004) and on coughing (p < 0.01) than patients with oxycodone alone and more patients with Targin were dismissed with oral opioid dose than patients with oxycodone alone (p < 0.004). There were no differences in pain scores on POD 5 and 6, or in length of hospital stay, incidence of nausea, time to first dejection or opioid dose after dismission. CONCLUSION: Oral opioid analgesia with controlled-release oxycodone is an effective postoperative regimen after VATS and thoracoscopies. Our retrospective data indicate that Targin might be less effective analgesic than oxycodone after VATS and thoracoscopies with no improvement in bowel function in the immediate postoperative period. STUDY LIMITATIONS: The study design is retrospective in nature.
Assuntos
Oxicodona/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Cirurgia Torácica Vídeoassistida/métodos , Administração Oral , Analgésicos Opioides/administração & dosagem , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/diagnóstico , Estudos Retrospectivos , Toracoscopia/métodosRESUMO
Introduction: Prostate Specific Membrane Antigen Positron Emission Tomography (PSMA-PET) is routinely used for the staging of patients with prostate cancer, but data on response assessment are sparse and primarily stem from metastatic castration-resistant prostate cancer (mCRPC) patients treated with PSMA radioligand therapy. Still, follow-up PSMA-PET is employed in earlier disease stages in case of clinical suspicion of disease persistence, recurrence or progression to decide if localized or systemic treatment is indicated. Therefore, the prognostic value of PSMA-PET derived tumor volumes in earlier disease stages (i.e., hormone-sensitive prostate cancer (HSPC) and non-[177Lu]Lu-PSMA-617 (LuPSMA) therapy castration resistant prostate cancer (CRPC)) are evaluated in this manuscript. Methods: A total number of 73 patients (6 primary staging, 42 HSPC, 25 CRPC) underwent two (i.e., baseline and follow-up, median interval: 379 days) whole-body [68Ga]Ga-PSMA-11 PET/CT scans between Nov 2014 and Dec 2018. Analysis was restricted to non-LuPSMA therapy patients. PSMA-PETs were retrospectively analyzed and primary tumor, lymph node-, visceral-, and bone metastases were segmented. Body weight-adjusted organ-specific and total tumor volumes (PSMAvol: sum of PET volumes of all lesions) were measured for baseline and follow-up. PSMAvol response was calculated as the absolute difference of whole-body tumor volumes. High metastatic burden (>5 metastases), RECIP 1.0 and PSMA-PET Progression Criteria (PPP) were determined. Survival data were sourced from the cancer registry. Results: The average number of tumor lesions per patient on the initial PET examination was 10.3 (SD 28.4). At baseline, PSMAvol was strongly associated with OS (HR 3.92, p <0.001; n = 73). Likewise, response in PSMAvol was significantly associated with OS (HR 10.48, p < 0.005; n = 73). PPP achieved significance as well (HR 2.19, p <0.05, n = 73). Patients with hormone sensitive disease and poor PSMAvol response (upper quartile of PSMAvol change) in follow-up had shorter outcome (p < 0.05; n = 42). PSMAvol in bones was the most relevant parameter for OS prognostication at baseline and for response assessment (HR 31.11 p < 0.001; HR 32.27, p < 0.001; n = 73). Conclusion: PPP and response in PSMAvol were significantly associated with OS in the present heterogeneous cohort. Bone tumor volume was the relevant miTNM region for OS prognostication. Future prospective evaluation of the performance of organ specific PSMAvol in more homogeneous cohorts seems warranted.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/patologia , Pessoa de Meia-Idade , Seguimentos , Radioisótopos de Gálio , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Glutamato Carboxipeptidase II/metabolismo , Compostos Radiofarmacêuticos , Antígenos de Superfície/metabolismo , Isótopos de Gálio , Prognóstico , Lutécio/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Carga Tumoral , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Dipeptídeos/uso terapêuticoRESUMO
BACKGROUND: The role of local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies on prostate-specific membrane antigen (PSMA) positron emission tomography/computerized tomography (PET/CT) has scarcely been explored. Limited data are available to identify men who would benefit from RP; on the contrary, those more likely to benefit already have systemic disease. OBJECTIVE: We aimed to assess the predictors of prostate-specific antigen (PSA) persistence in surgically managed PCa patients with lymphadenopathies on a PSMA PET/CT scan by integrating clinical, magnetic resonance imaging (MRI), and PSMA PET/CT parameters. DESIGN, SETTING, AND PARTICIPANTS: We identified 519 patients treated with RP and extended lymph node dissection, and who received preoperative PSMA PET between 2017 and 2022 in nine referral centers. Among them, we selected 88 patients with nodal uptake at preoperative PSMA PET (miTxN1M0). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome was PSA persistence, defined as a PSA value of ≥0.1 ng/ml at the first measurement after surgery. Multivariable logistic regression models tested the predictors of PSA persistence. Covariates consisted of biopsy International Society of Urological Pathology (ISUP) grade group, clinical stage at MRI, and number of positive spots at a PET/CT scan. A regression tree analysis stratified patients into risk groups based on preoperative characteristics. RESULTS AND LIMITATIONS: Overall, lymph node invasion (LNI) was detected in 63 patients (72%) and 32 (36%) experienced PSA persistence after RP. At multivariable analyses, having more than two lymph nodal positive findings at PSMA PET, seminal vesicle invasion (SVI) at MRI, and ISUP grade group >3 at biopsy were independent predictors of PSA persistence (all p < 0.05). At the regression tree analysis, patients were stratified in four risk groups according to biopsy ISUP grade, number of positive findings at PET/CT, and clinical stage at MRI. The model depicted good discrimination at internal validation (area under the curve 78%). CONCLUSIONS: One out of three miN1M0 patients showed PSA persistence after surgery. Patients with ISUP grade 2-3, as well as patients with organ-confined disease at MRI and a single or two positive nodal findings at PET are those in whom RP may achieve the best oncological outcomes in the context of a multimodal approach. Conversely, patients with a high ISUP grade and extracapsular extension or SVI or more than two spots at PSMA PET should be considered as potentially affected by systemic disease upfront. PATIENT SUMMARY: Our novel and straightforward risk classification integrates currently available preoperative risk tools and should, therefore, assist physician in preoperative counseling of men candidates for radical treatment for prostate cancer with positive lymph node uptake at prostate-specific membrane antigen positron emission tomography.
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Linfadenopatia , Neoplasias da Próstata , Masculino , Humanos , Antígeno Prostático Específico , Próstata/diagnóstico por imagem , Próstata/cirurgia , Próstata/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Glândulas Seminais/patologia , Metástase Linfática/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Prostatectomia , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Linfadenopatia/patologia , Linfadenopatia/cirurgiaRESUMO
PURPOSE: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS: We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non-EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for NECTIN4 CNVs. RESULTS: NECTIN4 amplifications are frequent genomic events in muscle-invasive bladder cancer (TCGA bladder cancer data set: approximately 17%) and mUC (approximately 26% in our mUC cohorts). In mUC-EV, NECTIN4 amplification represents a stable genomic alteration during metastatic progression and associates with enhanced membranous NECTIN4 protein expression. Ninety-six percent (27 of 28) of patients with NECTIN4 amplifications demonstrated objective responses to EV compared with 32% (24 of 74) in the nonamplified subgroup (P < .001). In multivariable Cox analysis adjusted for age, sex, and Bellmunt risk factors, NECTIN4 amplifications led to a 92% risk reduction for death (hazard ratio, 0.08 [95% CI, 0.02 to 0.34]; P < .001). In the mUC-non-EV, NECTIN4 amplifications were not associated with outcomes. TCGA Pan-Cancer analysis demonstrated that NECTIN4 amplifications occur frequently in other cancers, for example, in 5%-10% of breast and lung cancers. CONCLUSION: NECTIN4 amplifications are genomic predictors of EV responses and long-term survival in patients with mUC.
Assuntos
Moléculas de Adesão Celular , Amplificação de Genes , Humanos , Moléculas de Adesão Celular/genética , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Anticorpos Monoclonais/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Hibridização in Situ Fluorescente , Variações do Número de Cópias de DNA , Idoso de 80 Anos ou mais , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia , NectinasRESUMO
Androgen deprivation therapy (ADT) alone has been the standard of care for many years in men with metastatic prostate cancer. Due to the limited survival under this monotherapy, many new treatment options have been developed in the last few years. Regarding hormone-sensitive prostate cancer, combination therapies of two or three agents of ADT, androgen receptor signaling inhibitors (ARSI) and chemotherapy have been established and led to a significant benefit in overall survival. Additionally, in patients with metastatic castration-resistant prostate cancer, there are many new therapeutic approaches. Chemotherapy alone has been the standard of care in this situation. In the last years, some new therapeutic options have been developed, which led to an improved survival after progression under chemotherapy. These therapies include ARSI, PARP inhibitors and Lu-PSMA radioligand therapy. The use of a bispecific T-cell engager (BiTE) in this setting is a new promising therapeutic approach, which has not been established as standard of care yet. The role of immunotherapy in prostate cancer is still under investigation. Overall, many new treatment options make prostate cancer therapy a challenging and promising field.
RESUMO
Robotic-assisted laparoscopic partial nephrectomy (RALPN) is becoming a standard treatment for localized renal tumors worldwide. Data on the learning curve (LC) of RALPN are still insufficient. In the present study, we have attempted to gain further insight in this area by evaluating the LC using cumulative summation analysis (CUSUM). A series of 127 robotic partial nephrectomies were performed by two surgeons at our center between January 2018 and December 2020. CUSUM analysis was used to evaluate LC for operative time (OT). The different phases of surgical experience were compared in terms of perioperative parameters and pathologic outcomes. In addition, multivariate linear regression analysis was used to confirm the results of the CUSUM analysis by adjusting the phases of surgical experience for the other confounding factors that may affect OT. The median age of patients was 62 years, mean BMI was 28, and mean tumor size was 32 mm. Tumor complexity was classified as low, intermediate, and high risk according to the PADUA score in 44%, 38%, and 18%, respectively. The mean OT was 205 min, and trifecta was achieved in 72.4%. According to the CUSUM diagram, the LC of OT was divided into three phases: initial learning phase (18 cases), plateau phase (20 cases), and mastery phase (subsequent cases). The mean OT was 242, 208, and 190 min in the first, second, and third phases, respectively (P < 0.001). Surgeon experience phases were significantly associated with OT in multivariate analysis considering other preoperative and operative parameters. Surgical outcome was comparable between the three phases in terms of complications and achievement of trifecta; hospital stay was shorter in the mastery phase than in the first 2 phases (4 days vs 5 days, P = 0.02). The LC for RALPN is divided into 3 performance phases with CUSUM. Mastery of surgical technique was achieved after performing 38 cases. The initial learning phase of RALPN has no negative impact on surgical and oncologic outcomes .
Assuntos
Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Curva de Aprendizado , Laparoscopia/métodos , Nefrectomia/métodos , Neoplasias Renais/cirurgia , Estudos RetrospectivosRESUMO
Intraoperative identification of positive resection margins (PRMs) in high-risk prostate cancer (PC) needs improvement. Cerenkov luminescence imaging (CLI) with 68Ga-PSMA-11 is promising, although limited by low residual activity and artificial signals. Here, we aimed to assess the value of CLI and flexible autoradiography (FAR) with 18F-PSMA-1007. Methods: Mice bearing subcutaneous PSMA-avid RM1-PGLS tumors were administered 18F-PSMA-1007, and PET/CT was performed. After the animals had been killed, organs were excised and measured signals in CLI and FAR CLI were correlated with tracer activity concentrations (ACs) obtained from PET/CT. For clinical assessment, 7 high-risk PC patients underwent radical prostatectomy immediately after preoperative 18F-PSMA PET/CT. Contrast-to-noise ratios (CNRs) were calculated for both imaging modalities in intact specimens and after incision above the index lesion. Results: In the heterotopic in vivo mouse model (n = 5), CLI did not detect any lesion. FAR CLI detected a distinct signal in all mice, with a lowest AC of 7.25 kBq/mL (CNR, 5.48). After incision above the index lesion of the prostate specimen, no increased signal was observed at the cancer area in CLI. In contrast, using FAR CLI, a signal was detectable in 6 of 7 patients. The AC in the missed index lesion was 1.85 kBq/mL, resulting in a detection limit of at least 2.06 kBq/mL. Histopathology demonstrated 2 PRMs, neither of which was predicted by CLI or FAR CLI. Conclusion: 18F-PSMA FAR CLI was superior to CLI in tracer-related signal detectability. PC was could be visualized in radical prostatectomy down to 2.06 kBq/mL. However, the detection of PRMs was limited. Direct anatomic correlation of FAR CLI is challenging because of the scintillator overlay.
Assuntos
Próstata , Neoplasias da Próstata , Humanos , Masculino , Animais , Camundongos , Próstata/diagnóstico por imagem , Próstata/cirurgia , Próstata/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Autorradiografia , Luminescência , Estudos de Viabilidade , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Radioisótopos de Gálio , Prostatectomia/métodosRESUMO
BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsy (TB) facilitate accurate detection of clinically significant prostate cancer (csPC). However, it remains unclear how targeted cores should be applied for accurate diagnosis of csPC. OBJECTIVE: To assess csPC detection rates for two target-directed MRI/transrectal ultrasonography (TRUS) fusion biopsy approaches, conventional TB and target saturation biopsy (TS). DESIGN, SETTING, AND PARTICIPANTS: This was a prospective single-center study of outcomes for transperineal MRI/TRUS fusion biopsies for 170 men. Half of the men (n = 85) were randomized to conventional TB with four cores per lesion and half (n = 85) to TS with nine cores. Biopsies were performed by three experienced board-certified urologists. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PC and csPC (International Society of Urological Pathology grade group ≥2) detection rates for systematic biopsy (SB), TB, and TS were analyzed using McNemar's test for intrapatient comparisons and Fisher's exact test for TS versus TB. A combination of targeted biopsy (TS or TB) and SB served as the reference. RESULTS AND LIMITATIONS: According to the reference, csPC was diagnosed for 57 men in the TS group and 36 men in the TB group. Of these, TS detected 57/57 csPC cases and TB detected 33/36 csPC cases (p = 0.058). Detection of Gleason grade group 1 disease was 10/12 cases with TS and 8/17 cases with TB (p = 0.055). In addition, TS detected 97% of 63 csPC lesions, compared to 86% with TB (p = 0.1). Limitations include the single-center design, the limited generalizability owing to the transperineal biopsy route, the lack of central review of pathology and radical prostatectomy correlation, and uneven distributions of csPC prevalence, Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesions, men with two or more PI-RADS ≥3 lesions, and prostate-specific antigen density between the groups, which may have affected the results. CONCLUSIONS: In our study, rates of csPC detection did not significantly differ between TS and TB. PATIENT SUMMARY: In this study, we investigated two targeted approaches for taking prostate biopsy samples after observation of suspicious lesions on prostate scans. We found that the rates of detection of prostate cancer did not significantly differ between the two approaches.
Assuntos
Próstata , Neoplasias da Próstata , Humanos , Masculino , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Estudos Prospectivos , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Ultrassonografia de Intervenção/métodos , BiópsiaRESUMO
In this prospective two-center feasibility study, we evaluate the diagnostic value of intraoperative ex vivo specimenPET/CT imaging of radical prostatectomy (RP) and lymphadenectomy specimens. Ten patients with high-risk prostate cancer underwent clinical prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) preoperatively on the day of surgery. Six patients received 68Ga-PSMA-11 and four 18F-PSMA-1007. Radioactivity of the resected specimen was measured again using a novel specimenPET/CT device (AURA10; XEOS Medical, Gent, Belgium) developed for intraoperative margin assessment. All index lesions of staging multiparametric magnetic resonance imaging could be visualized. Overall, specimenPET/CT correlated well with conventional PET/CT regarding detection of suspicious tracer foci (Pearson coefficient 0.935). In addition, specimenPET/CT demonstrated all lymph node metastases detected on conventional PET/CT (n = 3), as well as three previously undetected lymph node metastases. Importantly, all positive or close (<1 mm) surgical margins could be visualized in agreement with histopathology. In conclusion, specimenPET/CT enables detection of PSMA-avid lesions and warrants further investigation to tailor RP, based on a good correlation with final pathology. Future trials will prospectively compare ex vivo specimenPET/CT with a frozen section analysis for the detection of positive surgical margins and assessment of biochemical recurrence-free survival. Patient summary: In this report, we examined prostatectomy and lymphadenectomy specimens for suspicious positron emission tomography (PET) signals after preoperative tracer injection. It was found that in all cases, a good signal could be visualized, with a promising correlation of surface assessment compared with histopathology. We conclude that specimenPET imaging is feasible and may help improve oncological outcomes in the future.