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INTRODUCTION: Primary prostate cancer (PCa) can be visualized on prostate-specific membrane antigen positron emission tomography (PSMA-PET) with high accuracy. However, intraprostatic lesions may be missed by visual PSMA-PET interpretation. In this work, we quantified and characterized the intraprostatic lesions which have been missed by visual PSMA-PET image interpretation. In addition, we investigated whether PSMA-PET-derived radiomics features (RFs) could detect these lesions. METHODOLOGY: This study consists of two cohorts of primary PCa patients: a prospective training cohort (n = 20) and an external validation cohort (n = 52). All patients underwent 68Ga-PSMA-11 PET/CT and histology sections were obtained after surgery. PCa lesions missed by visual PET image interpretation were counted and their International Society of Urological Pathology score (ISUP) was obtained. Finally, 154 RFs were derived from the PET images and the discriminative power to differentiate between prostates with or without visually undetectable lesions was assessed and areas under the receiver-operating curve (ROC-AUC) as well as sensitivities/specificities were calculated. RESULTS: In the training cohort, visual PET image interpretation missed 134 tumor lesions in 60% (12/20) of the patients, and of these patients, 75% had clinically significant (ISUP > 1) PCa. The median diameter of the missed lesions was 2.2 mm (range: 1-6). Standard clinical parameters like the NCCN risk group were equally distributed between patients with and without visually missed lesions (p < 0.05). Two RFs (local binary pattern (LBP) size-zone non-uniformality normalized and LBP small-area emphasis) were found to perform excellently in visually unknown PCa detection (Mann-Whitney U: p < 0.01, ROC-AUC: ≥ 0.93). In the validation cohort, PCa was missed in 50% (26/52) of the patients and 77% of these patients possessed clinically significant PCa. The sensitivities of both RFs in the validation cohort were ≥ 0.8. CONCLUSION: Visual PSMA-PET image interpretation may miss small but clinically significant PCa in a relevant number of patients and RFs can be implemented to uncover them. This could be used for guiding personalized treatments.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Ácido Edético/análogos & derivados , Isótopos de Galio , Radioisótopos de Galio , Humanos , Masculino , Oligopéptidos , Prevalencia , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , RadiofármacosRESUMEN
INTRODUCTION: Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. Children or adults with VHL disease have one of > 300 known germline mutations of the VHL gene located on chromosome 3. They are prone to develop hemangioblastomas, extremely rarely starting at age 6, rarely at age 12-18, and, typically and almost all, as adults. There is a plethora of VHL-associated tumors and cysts, mainly in the kidney, pancreas, adrenals, reproductive organs, and central nervous system. Due to a lack of causal treatment, alleviation of symptoms and prevention of permanent neurological deficits as well as malignant transformation are the main task. Paucity of data and the nonlinear course of tumor progression make management of pediatric VHL patients with hemangioblastomas challenging. METHODS: The Freiburg surveillance protocol was developed by combining data from the literature and our experience of examinations of > 300 VHL patients per year at our university VHL center. RESULTS: Key recommendations are to start screening of patients at risk by funduscopy with dilated pupils for retinal tumors with admission to school and with MRI of the brain and spinal cord at age 14, then continue biannually until age 18, with emergency MRI in case of neurological symptoms. Indication for surgery remains personalized and should be approved by an experienced VHL board, but we regard neurological symptoms, rapid tumor growth, or critically large tumor/cyst sizes as the key indications to remove hemangioblastomas. Since repeated surgery on hemangioblastomas in VHL patients is not rare, modern neurosurgical techniques should encompass microsurgery, neuronavigation, intraoperative neuromonitoring, fluorescein dye-based intraoperative angiography, intraoperative ultrasound, and minimally invasive approaches, preceded in selected cases by endovascular embolization. Highly specialized neurosurgeons are able to achieve a very low risk of permanent morbidity for the removal of hemangioblastomas from the cerebellum and spinal cord. Small retinal tumors of the peripheral retina can be treated by laser coagulation, larger tumors by cryocoagulation or brachytherapy. CONCLUSION: We consider management at experienced VHL centers mandatory and careful surveillance and monitoring of asymptomatic lesions are required to prevent unnecessary operations and minimize morbidity.
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Hemangioblastoma , Neoplasias de la Médula Espinal , Enfermedad de von Hippel-Lindau , Adolescente , Adulto , Niño , Antecedentes Genéticos , Hemangioblastoma/diagnóstico por imagen , Hemangioblastoma/genética , Hemangioblastoma/cirugía , Humanos , Procedimientos Neuroquirúrgicos , Neoplasias de la Médula Espinal/diagnóstico por imagen , Neoplasias de la Médula Espinal/genética , Neoplasias de la Médula Espinal/cirugía , Enfermedad de von Hippel-Lindau/genética , Enfermedad de von Hippel-Lindau/cirugíaRESUMEN
BACKGROUND: Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5-7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns. METHODS: We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases. RESULTS: At 1% false discovery rate, we identified > 3900 proteins, of which > 2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO. CONCLUSION: We present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.
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PURPOSE: Intraoperative identification of lymph node (LN) metastases (LNM) detected on preoperative PSMA PET/CT may be facilitated by PSMA radioguided surgery with the use of a gamma probe. We evaluated the uptake of 111In-labelled PSMA ligand DKFZ-617 (referred to as 111In-PSMA-617) in unaffected LN and LNM at the level of single LN. METHODS: Six patients with prostate cancer (PCa) with suspicion of LNM on preoperative PSMA PET/CT underwent 111In-PSMA-617-guided lymphadenectomy (LA; four salvage LA and two primary LA). 111In-PSMA-617 (109 ± 5 MBq). was injected Intravenously 48 h prior to surgery Template LAs were performed in small subregions: common, external, obturator and internal iliac vessels, and presacral and retroperitoneal subregions (n = 4). Samples from each subregion were isolated aiming at the level of single LN. Uptake was measured ex situ using a germanium detector. Receiver operating characteristic (ROC) analysis was performed based on 111In-PSMA-617 uptake expressed as standardized uptake values normalized to lean body mass (SUL). RESULTS: Overall 310 LN (mean 52 ± 19.7) were removed from 74 subregions (mean 12 ± 3.7). Of the 310 LN, 35 turned out to be LNM on histopathology. Separation of the samples from all subregions resulted in 318 single specimens: 182 PCa-negative LN samples with 275 LN, 35 single LNM samples, 3 non-nodal PCa tissue samples and 98 fibrofatty tissue samples. The median SULs of nonaffected LN (0.16) and affected LN (13.2) were significantly different (p < 0.0001). Based on 38 tumour-containing and 182 tumour-free specimens, ROC analysis revealed an area under the curve of 0.976 (95% CI 0.95-1.00, p < 0.0001). Using a SUL cut-off value of 1.136, sensitivity, specificity, positive predictive value, negative predictive value and accuracy in discriminating affected from nonaffected LN were 92.1% (35/38), 98.9% (180/182), 94.6% (35/37), 98.4% (180/183) and 97.7% (215/220), respectively. CONCLUSION: Ex situ analysis at the level of single LN showed that 111In-PSMA-617 had excellent ability to discriminate between affected and nonaffected LN in our patients with PCa. This tracer characteristic is a prerequisite for in vivo real-time measurements during surgery.
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Dipéptidos/metabolismo , Compuestos Heterocíclicos con 1 Anillo/metabolismo , Radioisótopos de Indio , Escisión del Ganglio Linfático , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Anciano , Transporte Biológico , Humanos , Marcaje Isotópico , Metástasis Linfática , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Trazadores RadiactivosRESUMEN
PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) is widely used in radiation treatment planning of primary prostate cancer (PCA). Focal dose escalation to the dominant intraprostatic lesions (DIPL) may lead to improved PCA control. Prostate-specific membrane antigen (PSMA) is overexpressed in most PCAs. (68)Ga-labelled PSMA inhibitors have demonstrated promising results in detection of PCA with PET/CT. The aim of this study was to compare (68)Ga-PSMA PET/CT with MRI for gross tumour volume (GTV) definition in primary PCA. METHODS: This retrospective study included 22 patients with primary PCA analysed after (68)Ga-PSMA PET/CT and mpMRI. GTVs were delineated on MR images by two radiologists (GTV-MRIrad) and two radiation oncologists separately. Both volumes were merged leading to GTV-MRIint. GTVs based on PET/CT were delineated by two nuclear medicine physicians in consensus (GTV-PET). Laterality (left, right, and left and right prostate lobes) on mpMRI, PET/CT and pathological analysis after biopsy were assessed. RESULTS: Mean GTV-MRIrad, GTV-MRIint and GTV-PET were 5.92, 3.83 and 11.41 cm(3), respectively. GTV-PET was significant larger then GTV-MRIint (p = 0.003). The MRI GTVs GTV-MRIrad and GTV-MRIint showed, respectively, 40 % and 57 % overlap with GTV-PET. GTV-MRIrad and GTV-MRIint included the SUVmax of GTV-PET in 12 and 11 patients (54.6 % and 50 %), respectively. In nine patients (47 %), laterality on mpMRI, PET/CT and histopathology after biopsy was similar. CONCLUSION: Ga-PSMA PET/CT and mpMRI provided concordant results for delineation of the DIPL in 47 % of patients (40 % - 54 % of lesions). GTV-PET was significantly larger than GTV-MRIint. (68)Ga-PSMA PET/CT may have a role in radiation treatment planning for focal radiation to the DIPL. Exact correlation of PET and MRI images with histopathology is needed.
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Imagen por Resonancia Magnética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Planificación de la Radioterapia Asistida por Computador , Anciano , Anciano de 80 o más Años , Ácido Edético/análogos & derivados , Isótopos de Galio , Radioisótopos de Galio , Humanos , Masculino , Persona de Mediana Edad , Oligopéptidos , Compuestos Organometálicos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Radiofármacos , Dosificación Radioterapéutica , Carga TumoralRESUMEN
PURPOSE: We evaluated the diagnostic accuracy of choline positron emission tomography/computerized tomography for nodal relapse of prostate cancer according to topographical site and tumor infiltration size in lymph nodes. MATERIALS AND METHODS: A total of 72 patients with nodal prostate cancer relapse after primary therapy underwent pelvic and/or retroperitoneal salvage lymph node dissection. Salvage was done after whole body positron emission tomography/computerized tomography with (11)C-choline or (18)F-fluoroethylcholine showed positron emission tomography positive lymph nodes but no other detectable metastasis. Diagnostic accuracy was evaluated in 160 dissected lymph node regions (pelvic left/right and retroperitoneal), 498 subregions (common, external and internal iliac, obturator, presacral, aortic bifurcation, aortal, vena caval and interaortocaval) and 2,122 lymph nodes. RESULTS: Lymph node metastasis was present in 32% of resected lymph nodes (681 of 2,122), resulting in 238 positive subregions and 111 positive regions. Positron emission tomography/computerized tomography was positive for 110 regions and 209 subregions. Sensitivity, specificity, positive and negative predictive values, and accuracy were 91.9%, 83.7%, 92.7%, 82.0% and 89.4% (region based), 80.7%, 93.5%, 91.9%, 84.1% and 87.3% (subregion based), and 57.0%, 98.4%, 94.5%, 82.6% and 84.9% (lesion based), respectively. Of 393 positive lymph node metastases detected by this method 278 (70.7%) were in lymph nodes with a less than 10 mm short axis diameter. Imaging sensitivity was 13.3%, 57.4% and 82.8% for a tumor infiltration depth of 2 or greater to less than 3 mm, 5 or greater to less than 6 mm and 10 or greater to less than 11 mm, respectively. Lymph node metastasis site and the radiotracer ((11)C-choline/(18)F-fluoroethylcholine) had no substantial impact on diagnostic accuracy. CONCLUSIONS: Choline positron emission tomography/computerized tomography detects affected lymph node regions (pelvic left/right and retroperitoneal) in patients with prostate cancer relapse with high accuracy and it seems helpful for guiding salvage lymph node dissection. Sensitivity decreases with the size of metastatic infiltration in lymph nodes. This technique detects metastasis in a significant fraction of lymph nodes that are not pathologically enlarged on computerized tomography.
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Radioisótopos de Carbono , Colina/análogos & derivados , Recurrencia Local de Neoplasia/diagnóstico , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico , Tomografía Computarizada por Rayos X , Anciano , Humanos , Metástasis Linfática/diagnóstico , Masculino , Imagen Multimodal , Estudios RetrospectivosRESUMEN
PURPOSE: (18)F-Fluoroethylcholine ((18)F-FECh) is excreted via the urinary system with high activity accumulation in the urinary bladder. Furosemide and oral hydration can be administered concomitantly to reduce urinary activity to provide better detectability of retroperitoneal and pelvic lesions. Currently it is unknown if there is any effect of furosemide on (18)F-FECh uptake in organs, tissues and tumour lesions and the extent to which image quality along the urinary tract may be improved by furosemide. METHODS: We retrospectively analysed 217 (18)F-FECh PET/CT examinations from 213 patients with known prostate cancer (PCa), performed either with oral hydration (109) or furosemide 20 mg together with oral hydration (108). Maximum (18)F-FECh uptake in different organs, tissues, lymph nodes and osseous metastases was quantified in terms of standardized uptake value (SUV) in a volume of interest and compared between the two groups. To characterize the impact of furosemide on lesion detectability a three-point rating scale was used to assess the presence of focal activity spots in the ureters and of perivesicular artefacts. RESULTS: Patient characteristics and distribution of tumour lesions were well balanced between the two groups. Overall, SUVmax values from normal organs were increased after furosemide compared to the values in patients scanned without furosemide. Significant changes were observed in the salivary glands, liver, spleen, pancreas, kidneys, gluteus muscle and perirenal fat. SUVmax values were significantly decreased after furosemide in lymph node metastases (SUVmax 4.81 ± 2.68 vs. 6.48 ± 4.22, p = 0.0006), but not in osseous metastases. Evaluation of image quality along the urinary tract revealed significantly better depiction of the perivesicular space and significantly less focal tracer accumulation in the ureters in patients receiving furosemide, but the number of detected lymph nodes was not significantly different. CONCLUSION: Furosemide administration reduced choline uptake in tumour lesions, especially significant in pelvic lymph node metastases. Although furosemide administration improved image quality, optimal image quality may also be obtained by adequate hydration without the risk of diminishing choline uptake in PCa lesions. Therefore a controlled hydration protocol seems more appropriate than administration of furosemide.
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Colina/análogos & derivados , Furosemida/farmacología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Anciano , Transporte Biológico/efectos de los fármacos , Colina/metabolismo , Fluorodesoxiglucosa F18 , Humanos , Masculino , Metástasis de la Neoplasia , Especificidad de Órganos , Neoplasias de la Próstata/patología , Control de Calidad , Cintigrafía , Estudios Retrospectivos , Sistema Urinario/diagnóstico por imagen , Sistema Urinario/efectos de los fármacos , Sistema Urinario/metabolismo , UrografíaRESUMEN
BACKGROUND: The role of autosomal dominant polycystic kidney disease (ADPKD) as a risk factor for renal cell carcinoma (RCC) is still under discussion. Data on prevalence of RCC in ADPKD are limited, especially on a large population scale. The aim of this study was to analyze the prevalence of RCC in ADPKD kidneys and characterize the clinical features of this coincidence. METHODS: Based on our histopathological registry for ADPKD and the Else Kröner-Fresenius Registry, we retrospectively reviewed malignant and benign renal lesions in patients with ADPKD who had undergone renal surgery from 1988 to 2011. RESULTS: 240 ADPKD patients underwent 301 renal surgeries. Mean age at surgery was 54 years. Overall, 16 malignant and 11 benign lesions were analyzed in 301 kidneys (5.3%; 3.7%), meaning that 12/240 (5%; 1:20) patients presented with malignant renal lesions. 66.7% (8/12) of these patients had undergone dialysis prior to surgery. We found 10/16 (63%) papillary RCC, 5/16 (31%) clear cell RCC, and 1/16 (6%) papillary noninvasive urothelial cancer. Regarding all renal lesions, 6/17 (35.3%) patients had more than one histological finding in their kidneys. In 2 cases, metachronous metastases were removed. Mean follow-up was 66.7 months. CONCLUSION: Kidney-related prevalence of RCC in ADPKD kidneys was surprisingly high. Whether or not this is due to chronic dialysis or due to the underlying disease is still speculative. Like other cystic renal diseases with an increased risk for RCC, the attending physician should be aware of the malignant potential of ADPKD, especially with concomitant dialysis.
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Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/patología , Neoplasias Renales/epidemiología , Neoplasias Renales/patología , Riñón Poliquístico Autosómico Dominante/epidemiología , Riñón Poliquístico Autosómico Dominante/patología , Diálisis Renal/estadística & datos numéricos , Carcinoma de Células Renales/cirugía , Comorbilidad , Femenino , Alemania/epidemiología , Humanos , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/cirugía , Prevalencia , Medición de RiesgoRESUMEN
Quantitative evaluation of prostate-specific membrane antigen (PSMA)-targeting PET/CT remains challenging but is urgently needed for the use of standardized PET-based response criteria, such as the PSMA PET/CT consensus statement or Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0). A recent study evaluated the prognostic value of whole-body tumor volume using a semiautomatic method relying on a 50% threshold of lesion SUVmax (PSMATV50). In the present study, we analyzed the suitability of this approach comparing 18F-PSMA-1007 with 68Ga-PSMA-11 PET/CT scans and the potential of PSMATV50 for the prediction of overall survival (OS) in patients before 177Lu-PSMA radioligand therapy (RLT). Moreover, PSMATV50 was integrated into the PSMA PET/CT consensus statement as well as RECIP 1.0, and the prognostic value of these response classification systems was compared. Methods: This retrospective study included 70 patients with metastatic castration-resistant prostate cancer undergoing PSMA RLT. Thirty-three patients were monitored by 68Ga-PSMA-11 PET/CT, and 37 patients by 18F-PSMA-1007 PET/CT. PET/CT scans before (baseline) and at the end of PSMA RLT after 2-4 cycles (follow-up) were separately analyzed by 2 readers. PSMATV50 at baseline and its change at the time of follow-up (ΔPSMATV50, expressed as a ratio) were correlated with OS using Cox proportional-hazards regression. The results of both subgroups were compared. The integration of ΔPSMATV50 in existing response classification systems was evaluated. To assess and compare the discriminatory strength of these classification systems, Gönen and Heller concordance probability estimates were calculated. Results: PSMATV50 determination was technically feasible in all examinations. A higher PSMATV50 at baseline and a higher ΔPSMATV50 were strongly associated with a shorter OS for both 68Ga-PSMA-11 (PSMATV50: hazard ratio [HR] of 1.29 [95% CI, 1.05-1.55], P = 0.009; ΔPSMATV50: HR of 1.83 [95% CI, 1.08-3.09], P = 0.024) and 18F-PSMA-1007 (PSMATV50: HR of 1.84 [95% CI, 1.13-2.99], P = 0.014; ΔPSMATV50: HR of 1.23 [95% CI, 1.04-1.51], P = 0.03). Response assessment provided high discriminatory power for OS for the PSMA PET/CT consensus statement (concordance probability estimate, 0.73) as well as RECIP 1.0 (concordance probability estimate, 0.74). Conclusion: PSMATV50 and ΔPSMATV50 proved to be predictive of OS not only for 68Ga-PSMA-11 but also for 18F-PSMA-1007 PET/CT scans. Subsequent integration of ΔPSMATV50 into the PSMA PET/CT consensus statement and RECIP 1.0 provided equally high prognostic value for both classification systems.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Pronóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Antígeno Prostático Específico , Carga Tumoral , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Dipéptidos/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , LutecioRESUMEN
Introduction: Robot-assisted radical prostatectomy (RARP) is a surgical treatment option for prostate cancer (PC). Quality in RARP depends on the surgeon´s operative volume and expertise. When implementing RARP, it is standard practice to hire a pre-trained surgeon. The aim of our study was to investigate the transferability of quality in RARP. Patients and Methods: We analyzed two consecutive retrospective cohorts of 100 and 108 men, respectively, who underwent RARP at two different centers and on whom surgery was performed by the same surgeon. Results: There were more men with high-grade PC in Cohort 1: 25/100 (25.0%) vs. 9/108 (8.3%), p < 0.01, and infiltration of the seminal vesicles was more frequent (23/100 (23.0%) vs. 10/108 (9.2%), p < 0.01). In Cohort 2, the duration of surgery was shorter and blood loss was lower: 149 (134−174) vs. 172 min (150−196), p < 0.01 and 300 (200−400) vs. 131 (99−188) mL, p < 0.01. No difference was found in the proportion of positive surgical margins in the T2 cohort (8.8% vs. 8.2%, p = 1.00). Conclusion: The procedural and oncological outcome parameters of Cohort 2 do not appear to be inferior to the results obtained for the first cohort. The quality of RARP is transferable if a pre-trained surgeon is hired.
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ABSTRACT: A 71-year-old man presented with chronic anemia (hemoglobin 7.3 g/dL). Further serum analyses showed elevated prostate-specific antigen (13 ng/mL), suggestive of prostate cancer. However, ultrasound-guided transrectal sextant biopsy did not find any evidence of prostate cancer. In order to improve guidance of intended repeated biopsy, [ 18 F]prostate-specific membrane antigen (PSMA) 1007 PET/CT was performed, which showed a solitary lesion with strong PSMA expression in the left peripheral zone in the prostate gland. Surprisingly, also a diffuse bone marrow involvement with predominantly osteolytic lesions was observed. This massive osseous tumor burden was clearly discordant to the only relatively mild elevated prostate-specific antigen. The subsequent bone biopsy revealed multiple myeloma. This case does not only highlight a possible pitfall on PSMA PET/CT, but also raises the question on how far PSMA ligands may offer diagnostic and therapeutic potential in multiple myeloma.
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Mieloma Múltiple , Neoplasias de la Próstata , Anciano , Médula Ósea/patología , Radioisótopos de Galio , Humanos , Masculino , Mieloma Múltiple/diagnóstico por imagen , Niacinamida/análogos & derivados , Oligopéptidos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Medicina de Precisión , Antígeno Prostático Específico , Neoplasias de la Próstata/patologíaRESUMEN
Background: In prostate cancer (PC) diagnosis, additional systematic biopsy (SB) is recommended to complement MRI-targeted biopsy (TB) to address the limited sensitivity of TB alone. The combination of TB+SB is beneficial for diagnosing additional significant PC (sPC) but harmful in terms of the additional diagnosis of indolent PC (iPC), morbidity, and resource expenditures. We aimed to investigate the benefit of additional SB and to identify predictors for this outcome. Methods: We analyzed the frequency of upgrading to sPC by additional SB in a retrospective single-center cohort of 1043 men. Regression analysis (RA) was performed to identify predictors for this outcome. Reclassification rates of ISUP grade groups between prostate biopsy and a subsequent radical prostatectomy were assessed. Results: Additional SB led to upgrading to sPC in 98/1043 men (9.4%) and to the additional diagnosis of iPC in 71/1043 (6.8%). In RA, men harboring a PI-RADS 2-4 lesion were more likely to have TB results upgraded by SB (p < 0.01) compared to PI-RADS 5 men. When analyzing reclassification rates, additional SB reduced the upgrading to sPC from 43/214 (20.1%) to 8/214 (3.7%). In the PI-RADS 5 subgroup, this difference decreased: 4/87 (4.7%) with TB only vs. 1/87 (1.2%) with TB+SB. Conclusion: Men with a PI-RADS 5 lesion may obviate additional SB.
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Von Hippel-Lindau disease (VHL) is a hereditary disorder associated with malignant tumors including clear cell renal cell carcinoma (ccRCC). Partial nephrectomy is complicated by multilocular tumor occurrence and a high recurrence rate. The aim of this study was to evaluate the potential of stereotactic body radiotherapy (SBRT) as an alternative treatment approach in VHL patients with multiple ccRCC. Patients with VHL and a diagnosis of ccRCC were enrolled. SBRT was conducted using five fractions of 10 Gy or eight fractions of 7.5 Gy. The primary endpoint was local control (LC). Secondary endpoints included alteration of renal function and adverse events. Seven patients with a total of eight treated lesions were enrolled. Median age was 44 years. Five patients exhibited multiple bilateral kidney cysts in addition to ccRCC. Three patients underwent at least one partial nephrectomy in the past. After a median follow-up of 43 months, 2-year LC was 100%, while 2-year CSS, 2-year PFS and 2-year OS was 100%, 85.7% and 85.7%, respectively. SBRT was very well tolerated with no acute or chronic toxicities grade ≥ 2. Mean estimated glomerular filtration rate (eGFR) at baseline was 83.7 ± 13.0 mL/min/1.73 m2, which decreased to 76.6 ± 8.0 mL/min/1.73 m2 after 1 year. Although the sample size was small, SBRT resulted in an excellent LC rate and was very well tolerated with preservation of kidney function in patients with multiple renal lesions and cysts.
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This case series highlights the role of repeat salvage lymph node dissection (sLND) for nodal-recurrent prostate cancer. We provide a descriptive analysis of ten patients who underwent sLND in a total of 23 surgeries (mean 2.3 sLNDs per patient) and their long-term follow-up (median of 158 mo after radical prostatectomy). A complete prostate-specific antigen response was observed in nine/23 cases (39.1%), and an incomplete response in 14 (60.9%). Analysis by anatomical location revealed a trend towards more distant metastases on repeat surgery, with only three in-field recurrences in patients with previously positive nodes. Repeat sLND can be surgically challenging, and major intraoperative complications were observed in three/23 cases (13.0%). Repeat sLND for patients with nodal-recurrent prostate cancer seems to be a feasible treatment option, albeit only in carefully selected patients. Nevertheless, it remains a highly experimental approach with unclear oncological benefit.
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Recurrencia Local de Neoplasia , Neoplasias de la Próstata , Anciano , Humanos , Escisión del Ganglio Linfático/efectos adversos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Prostatectomía/efectos adversos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Terapia RecuperativaRESUMEN
BACKGROUND: To investigate infectious and non-infectious complications after transperineal prostate biopsy (TPB) without antibiotic prophylaxis in a multicenter cohort. Secondly, to identify whether increasing the number of cores was predictive for the occurrence of complications. Thirdly, to examine the relation between TPB and erectile dysfunction. METHODS: We analyzed a retrospective multicenter cohort of 550 patients from three different urological centers undergoing TPB without antibiotic prophylaxis. The median number of cores was 26. Demographic and clinical data were extracted by reviewing patients' electronic medical records and follow-up data such as postoperative complications obtained by structured phone interviews. To investigate the influence of the number of cores taken on the occurrence of complications, we performed univariate and multivariate mixed effects logistic regression models. RESULTS: There was no case of sepsis reported. Overall, 6.0% of patients (33/550) presented with any complication besides mild macrohematuria. In all, 46/47 (98%) complications were ≤Grade 2 according to Clavien-Dindo. In multivariate regression analyses, an increased number of cores was associated with overall complications (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.02-1.14, P = 0.01) and specifically bleeding complications (OR 1.28, 95% CI 1.11-1.50, P = 0.01) but not with infectious complications (OR 1.03, 95% CI 0.97-1.10, P = 0.67). A total of 14.4% of patients referred impairment of erectile function after TPB. Of note, 98% of these men were diagnosed with prostate cancer. CONCLUSIONS: This is the first multicenter trial to investigate complications after TPB without antibiotic prophylaxis. In our study, we found no case of sepsis. This underlines the safety advantage of TPB even without antibiotic prophylaxis and supports the ongoing initiative to abandon TRB of the prostate. A higher number of cores were associated with an increase in overall complications specifically bleeding complications, but not with infectious complications. Post-biopsy erectile dysfunction was mainly present in patients diagnosed with PCa.
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Disfunción Eréctil , Neoplasias de la Próstata , Sepsis , Antibacterianos/uso terapéutico , Biopsia/efectos adversos , Disfunción Eréctil/patología , Estudios de Seguimiento , Humanos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Masculino , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Próstata/patología , Neoplasias de la Próstata/patología , Sepsis/epidemiología , Sepsis/etiología , Sepsis/prevención & controlRESUMEN
Introduction: Accurate detection and segmentation of the intraprostatic gross tumor volume (GTV) is pivotal for radiotherapy (RT) in primary prostate cancer (PCa) since it influences focal therapy target volumes and the patients' cT stage. The study aimed to compare the performance of multiparametric resonance imaging (mpMRI) with [18F] PSMA-1007 positron emission tomography (PET) for intraprostatic GTV detection as well as delineation and to evaluate their respective influence on RT concepts. Materials and Methods: In total, 93 patients from two German University Hospitals with [18F] PSMA-1007-PET/CT and MRI (Freiburg) or [18F] PSMA-1007-PET/MRI (Dresden) were retrospectively enrolled. Validated contouring techniques were applied for GTV-PET and -MRI segmentation. Absolute tumor volume and cT status were determined for each imaging method. The PCa distribution from histopathological reports based on biopsy cores and surgery specimen was used as reference in terms of laterality (unilateral vs. bilateral). Results: In the Freiburg cohort (n = 84), mpMRI and PET detected in median 2 (range: 1-5) and 3 (range: 1-8) GTVs, respectively (p < 0.01). The median GTV-MRI was significantly smaller than the GTV-PET, measuring 2.05 vs. 3.65 ml (p = 0.0005). PET had a statistically significant higher concordance in laterality with surgery specimen compared to mpMRI (p = 0.04) and biopsy (p < 0.01), respectively. PSMA PET led to more cT2c and cT3b stages, whereas cT3a stage was more pronounced in mpMRI. Based on the cT stage derived from mpMRI and PET information, 21 and 23 as well as 59 and 60 patients, respectively, were intermediate- and high-risk according to the National Comprehensive Cancer Network (NCCN) v1.2022 criteria. In the Dresden cohort (n = 9), similar results were observed. Conclusion: Intraprostatic GTV segmentation based on [18F] PSMA-1007 PET results in more and larger GTVs compared to mpMRI. This influences focal RT target volumes and cT stage definition, but not the NCCN risk group.
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BACKROUND: Accurate surrogate parameters for radio resistance are warranted for individualized radiotherapy (RT) concepts in prostate cancer (PCa). The purpose of this study was to assess intertumoral heterogeneity in terms of radio resistance using an ex-vivo γH2AX assay after irradiation of prostate biopsy cores and to investigate its correlation with clinical features of respective patients as well as imaging and genomic features of tumor areas. METHODS: Twenty one patients with histologically-proven PCa and pre-therapeutic multiparametric resonance imaging and prostate-specific membrane antigen positron emission tomography were included in the study. Biopsy cores were collected from 26 PCa foci. Residual γH2AX foci were counted 24 h after ex-vivo irradiation (with 0 and 4 Gy) of biopsy specimen and served as a surrogate for radio resistance. Clinical, genomic (next generation sequencing) and imaging features were collected and their association with the radio resistance was studied. RESULTS: In total 18 PCa lesions from 16 patients were included in the final analysis. The median γH2AX foci value per PCa lesion was 3.12. According to this, the patients were divided into two groups (radio sensitive vs. radio resistant) with significant differences in foci number (p < 0.0001). The patients in the radio sensitive group had significantly higher prostate specific antigen serum concentration (p = 0.015), tumor areas in the radio sensitive group had higher SUV (standardized uptake values in PSMA PET)-max and -mean values (p = 0.0037, p = 0.028) and lower ADC (apparent diffusion coefficient-mean values, p = 0.049). All later parameters had significant (p < 0.05) correlations in Pearson's test. One patient in the radio sensitive group displayed a previously not reported loss of function frameshift mutation in the NBN gene (c.654_658delAAAAC) that introduces a premature termination codon and results in a truncated protein. CONCLUSION: In this pilot study, significant differences in intertumoral radio resistance were observed and clinical as well as imaging parameters may be applied for their prediction. After further prospective validation in larger patient cohorts these finding may lead to individual RT dose prescription for PCa patients in the future.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Codón sin Sentido , Humanos , Masculino , Proyectos Piloto , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/radioterapia , Tolerancia a Radiación/genéticaRESUMEN
BACKGROUND: Systematic biopsy (SB) according to the Ginsburg scheme (GBS) is widely used to complement MRI-targeted biopsy (MR-TB) for optimizing the diagnosis of clinically significant prostate cancer (sPCa). Knowledge of the GBS's blind sectors where sPCa is missed is crucial to improve biopsy strategies. METHODS: We analyzed cancer detection rates in 1084 patients that underwent MR-TB and SB. Cancerous lesions that were missed or underestimated by GBS were re-localized onto a prostate map encompassing Ginsburg sectors and blind-sectors (anterior, central, basodorsal and basoventral). Logistic regression analysis (LRA) and prostatic configuration analysis were applied to identify predictors for missing sPCa with the GBS. RESULTS: GBS missed sPCa in 39 patients (39/1084, 3.6%). In 27 cases (27/39, 69.2%), sPCa was missed within a blind sector, with 17/39 lesions localized in the anterior region (43.6%). Neither LRA nor prostatic configuration analysis identified predictors for missing sPCa with the GBS. CONCLUSIONS: This is the first study to analyze the distribution of sPCa missed by the GBS. GBS misses sPCa in few men only, with the majority localized in the anterior region. Adding blind sectors to GBS defined a new sector map of the prostate suited for reporting histopathological biopsy results.
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STUDY AIMS: To investigate safety and side effects of transperineal prostate biopsy without antibiotic prophylaxis. Secondary aim was to identify whether the number of cores influenced the occurrence of complications. PATIENTS AND METHODS: A cohort of 184 patients undergoing perineal prostate biopsy without antibiotic prophylaxis from 2015 to 2017 was analyzed retrospectively. On average, 41 cores were taken via two perineal skin punctures. Demographic and clinical data were obtained from patients´ electronic medical records. Binary logistic regression was performed to identify predictors for complications with the following covariates: age, prostate specific antigen (PSA), prostate volume, Prostate Imaging Reporting and Data System score, history of prostatitis, therapeutic anticoagulation, risk factors for urinary tract infection, surgery duration, and the number of biopsy cores. Furthermore, we calculated chi-squared tests with post hoc analyses for differences in the occurrence of complications between quartiles of the above-mentioned parameters. RESULTS: The overall complication rate was 10.8% (20/185). Out of 20, 19 (95 %) complications were ≤ grade 2 according to the Clavien-Dindo classification. There were two cases of afebrile urinary tract infection, and no patient developed fever or sepsis. Acute urinary retention was reported in 10 patients (5.4 %). The total number of cores was not associated to infectious complications or acute urinary retention rates. CONCLUSIONS: Transperineal prostate biopsy without antibiotic prophylaxis is a safe procedure. Neither postoperative fever nor sepsis occurred. An increased number of cores through two skin punctures was not associated with more complications.