| 1. |
- Acosta Ruiz, Vanessa, et al.
(author)
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Periprocedural outcome after laparoscopic partial nephrectomy versus radiofrequency ablation for T1 renal tumors : A modified R.E.N.A.L nephrometry score adjusted comparison
- 2019
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In: Acta Radiologica. - : Sage Publications. - 0284-1851 .- 1600-0455. ; 60:2, s. 260-268
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Journal article (peer-reviewed)abstract
- Background: Comparable oncological outcomes have been seen after surgical nephrectomy and thermal ablation of renal tumors recently. However, periprocedural outcome needs to be assessed for aiding treatment decision.Purpose: To compare efficacy rates and periprocedural outcome (technical success, session time, hospitalization time, and complications) after renal tumor treatment with laparoscopic partial nephrectomy (LPN) or radiofrequency ablation (RFA).Material and Methods: The initial experience with 49 (treated with LPN) and 84 (treated with RFA) consecutive patients for a single renal tumor (diameter ≤ 5 cm, limited to the kidney) during 2007-2014 was evaluated. Patient and tumor characteristics, efficacy rates, and periprocedural outcome were collected retrospectively. The stratified Mantel Haenzel and Van Elteren tests, adjusted for tumor complexity (with the modified R.E.N.A.L nephrometry score [m-RNS]), were used to assess differences in treatment outcomes.Results: Primary efficacy rate was 98% for LPN and 85.7% for RFA; secondary efficacy rate was 93.9% for LPN and 95.2% for RFA; and technical success rate was 87.8% for LPN and 100% for RFA. Median session (m-RNS adjusted P < 0.001; LPN 215 min, RFA 137 min) and median hospitalization time were longer after LPN (m-RNS adjusted P < 0.001; LPN 5 days, RFA 2 days). Side effects were uncommon (LPN 2%, RFA 4.8%). Complications were more frequent after LPN (m-RNS adjusted P < 0.001; LPN 42.9%, RFA 10.7%).Conclusion: Both methods achieved equivalent secondary efficacy rates. RFA included several treatment sessions, but session and hospitalization times were shorter, and complications were less frequent than for LPN. The differences remained after adjustment for renal tumor complexity.
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| 2. |
- Al-Mashhadi, Ammar, et al.
(author)
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Changes of arterial pressure following relief of obstruction in adults with hydronephrosis
- 2018
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 123:4, s. 216-224
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Journal article (peer-reviewed)abstract
- Background: As much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery.Materials and methods: Medical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients (35 years old; 95% CI 29–39). Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney.Results: Systolic (−11 mmHg; 95% CI 6–15 mmHg), diastolic (−8 mmHg; 95% CI 4–11 mmHg), and mean arterial (-9 mmHg; 95% CI 6–12) pressures were significantly reduced after relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37–41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction.Conclusions: In adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis.
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| 3. |
- Eldh, Maria, et al.
(author)
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Proteomic Profiling of Tissue Exosomes Indicates Continuous Release of Malignant Exosomes in Urinary Bladder Cancer Patients, Even with Pathologically Undetectable Tumour
- 2021
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In: Cancers. - : MDPI. - 2072-6694. ; 13:13
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Journal article (peer-reviewed)abstract
- Simple Summary Urinary bladder cancer (UBC) has a high recurrence rate, and biomarkers for different treatment strategies are highly needed. This study investigated the release of nanovesicles called exosomes from urinary bladder tissue from tumour-proximal sites as well as tumour-distant sites in transurethrally resected (TUR-B) patients with or without preoperative neoadjuvant chemotherapy prior to ensuing radical cystectomy-all without remaining visible tumour after TUR-B. We show that cancer-promoting exosomes were detected from both sites, suggesting that the previous tumour has altered the whole bladder tissue into a cancer-supporting milieu. The exosomes may originate from remaining pathologically undetectable cancer cells or transformed epithelial cells, and the study supports the notion of exosomes as mediators of metastatic spread and as potential biomarkers. It also supports early and radical removal of the bladder in urinary bladder cancer patients. Invasive urothelial bladder cancer (UBC) has high recurrence rates even after radical cystectomy (RC). Exosomes are membrane-bound nanovesicles, which have been shown to contribute to carcinogenesis and metastasis. We previously showed that urinary exosomes display a malignant profile in UBC patients despite the absence of detectable tumour. Here, we investigated exosomes from sampling sites close to or distant from the former tumour, aiming to understand the effect of the tumour on the local milieu. Ten patients scheduled for cystectomy after transurethral bladder resection (TUR-B), without remaining detectable tumour, were included. Exosomes were isolated from tissue explants of both the previous tumour site and distant bladder tissue. Proteins were quantified by mass spectrometry in seven patients. Exosomes from the previous tumour site were enriched in inflammatory but not cancer-related pathways compared to distant tissue. However, the 69 most abundant proteins in tissue-derived exosomes regardless of site, 20 of which were also found in urinary exosomes from our previous study, were enriched for cancer-related metabolic pathways and associated with poor prognosis in an external mRNA dataset. The enrichment of cancer-related pathways in the most abundant proteins, regardless of sampling site, confirms our hypothesis that despite the absence of detectable tumour, the entire bladder releases exosomes that contribute to metastasis and highlights the need for early RC.
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| 4. |
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| 5. |
- Häggman, Michael, et al.
(author)
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Bi-parametric MRI/TRUS fusion targeted repeat biopsy after systematic 10-12 core TRUS-guided biopsy reveals more significant prostate cancer especially in anteriorly located tumors
- 2022
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In: Acta Radiologica Open. - : SAGE Publications. - 2058-4601. ; 11:3
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Journal article (peer-reviewed)abstract
- Background: MRI and fusion guided biopsy have an increased role in the diagnosis of prostate cancer. Purpose: To demonstrate the possible advantages with Bi-parametric MRI fusion-guided repeat biopsy over systematic 10-12-core biopsy for the diagnosis of prostate cancer. Material and Methods: Four hundred and twenty-three consecutive men, with previous systematic 10-12-core TRUS-guided biopsy, and with suspicion of, or diagnosis of, low-risk prostate cancer underwent fusion-guided prostate biopsy between February 2015 and February 2017. The material was retrospectively assessed. In 220 cases no previous cancer was diagnosed, and in 203 cases confirmatory fusion guided biopsy was performed prior to active monitoring. MRI was classified according to PI-RADS. Systematic biopsy was compared to fusion guided biopsy for the detection of cancer, and PI-RADS was compared to the Gleason score. Results: Fusion guided biopsy detected significantly more cancers than systematic (p < .001). Gleason scores were higher in the fusion biopsy group (p < .001). Anterior tumors were present in 54% of patients. Fusion biopsy from these lesions showed cancer in 53% with previously negative biopsy in systematic biopsies and 66% of them were upgraded from low risk to intermediate or high-risk cancers. Conclusion: These results show superior detection rate and grading of bi-parametric MRI/TRUS fusion targeted repeat biopsy over systematic 10-12 core biopsies. Fusion guided biopsy detects more significant cancers despite using fewer cores. The risk group was changed for many patients initially selected for active surveillance due to upgrading of tumors. Bi-parametric MRI shows promising results in detecting anterior tumors in patients with suspected prostate cancer.
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| 6. |
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| 7. |
- Ladjevardi, Sam, et al.
(author)
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A Comparison of Different Imaging Techniques for Localisation of Cancers in the Prostate
- 2014
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In: Open Prostate Cancer Journal. - : Bentham Science Publishers Ltd.. - 1876-8229. ; 7, s. 1-6
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Journal article (peer-reviewed)abstract
- The diagnostic accuracy of standard transrectal ultrasound-guided (TRUL) biopsy is limited due to the finite number of cores that can be obtained. It has been shown that the technique is not sufficiently reliable in defining the location and extent of prostatic cancer. The main aim of this study was to investigate the effectiveness of magnetic resonance imaging (MRI), and positron emission tomography (PET/CT) imaging techniques in pinpointing potential tumour lesions prior to prostate biopsy.Material and methodsThe study cohort consisted of 45 men with a raised prostate specific-antigen (PSA) level and/or suspected prostate cancer (PCa) at digital rectal examinations (DRE). Of the 45 patients, 23 had PCa detected with core needle biopsy (CNB). All had 11C acetate PET/CT imaging. Ten of those 23 patients underwent radical prostatectomy (RP), of those ten patients, eight patients had MR spectroscopic imaging (MRSI) with 3 T and six had diffusion weighted imaging (DWI) with apparent diffusion coefficient calculation (MRI DWI ADC). CNB, PET/CT, 2D MRSI and ADC map results were compared with postoperative specimen histopathology.Results The sensitivity of CNB, PET/CT, MRSI and DWI ADC were 0.53, 0.55, 0.79 and 0.95, whereas the specificity of was 0.88, 0.87, 0.46 and 0.73, respectively.Conclusion MRI improves the PCa detection by defining the areas of interest for targeted CNB of the prostate and can reduce the number of biopsies required
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| 8. |
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| 9. |
- Ladjevardi, Sam
(author)
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Imaging and Treatment Outcome of Potentially Curable Prostate Cancer
- 2012
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Doctoral thesis (other academic/artistic)abstract
- The over-all aim of the present study was to compare the results of treatment with curative intent, with conservative treatment in men with prostate cancer (PCa) without distant metastases.In a population-based cohort in Sweden, the predictive value of prostate-specific antigen (PSA) was evaluated and the relative survival of men considered plausible candidates for treatment with curative intent was investigated.We also evaluated the association between curative treatment and cause-specific mortality, and over-all as well as relative survival in men diagnosed with PCa with a serum PSA level between 20 and 100 ng/ml.Due to the uncertainly of transrectal ultrasound-guided biopsy in the diagnosis of PCa, we created a model for prostate imaging to increase the safety of guided Core Needle Biopsy (CNB) in men with suspect PCa, thereby improving staging. Material and methods. The cohorts in the first three studies were prospectively included in a population-based register (the National Prostate Cancer Register). Study IV was a clinical study on patients included between 2010 and 2011.Results. Regardless of Gleason Score, a positive relationship between survival and serum PSA level categories in patients with a PSA level> 4 ng/ml was found, but a paradoxical inverse relationship was observed in men with a PSA level < 4 ng/ml. Men with a well-differentiated tumour had a 5-year relative survival exceeding 100% regardless of treatment. The survival rate for moderately and poorly differentiated tumours was poor for men managed conservatively. The 10-year cause-specific mortality for patients with PSA 20-50 ng/ml was 36% for patients treated without and 13% for patients treated with curative intent. For patients with a PSA 50-100 ng/ml the 10-year cause-specific mortality was 55% for conservative and 20% for patients treated with curative intent.PCa detection by CNB, magnetic resonance imaging (MR) with ADC (Apparent diffusion coefficient), magnetic resonance spectroscopic imaging (MRSI) and Positron Emission Tomography (PET/CT) ¹¹C Acetate imaging applied to 10 sections of the prostate demonstrated clear conformity between MRI ADC mapping and postoperative findings, showing high specificity (87%) and sensitivity (95%).Conclusion. The inverse relationship between relative survival and PSA at levels below 4 ng/ml should be considered when choosing a PSA cut-off level. Outcome differs little between conservative management and treatment with curative intent in men with localised well- to moderately differentiated tumours over a 10-yr period. For men with poorly differentiated tumours, on the other hand, choice of treatment is crucial for outcome. Treatment with curative intent is beneficial in the group of men with prostate cancer and PSA levels between 20 and 100 ng/ml without distant metastases. A combination of MRI , diffusion ADC and MRSI may provide an improved model for imaging of the prostate for targeted biopsy.
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| 10. |
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| 11. |
- Ladjevardi, Sam, et al.
(author)
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Prostate biopsy sampling causes hematogenous dissemination of epithelial cellular material
- 2014
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In: Disease Markers. - : Hindawi Limited. - 0278-0240 .- 1875-8630. ; , s. 707529-
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Journal article (peer-reviewed)abstract
- The extent of epithelial cellular material (ECM) occurring in venous blood samples after diagnostic core needle biopsy (CNB) was studied in 23 patients with CNB diagnosed prostate cancer without provable metastases and 15 patients without cancer. The data show a significant increase of ECM in the peripheral blood sampled 20 seconds or 30 minutes after the last of 10 CNB procedures compared to the number of ECM detectable in the blood samples taken before the performance of CNB. The data indicate that diagnostic CNB of prostate cancer causes an extensive tissue trauma with a potential risk of cancer cell dissemination.
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| 12. |
- Ladjevardi, Sam, et al.
(author)
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Treatment with curative intent and survival in men with high-risk prostate cancer. A population-based study of 11 380 men with serum PSA level 20-100 ng/mL
- 2013
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In: BJU International. - : Wiley-Blackwell. - 1464-4096 .- 1464-410X. ; 111:3, s. 381-388
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Journal article (peer-reviewed)abstract
- Objective less thanbrgreater than less thanbrgreater thanTo investigate the influence of curative treatment on cause-specific mortality in men diagnosed with prostate cancer (PCa) with serum prostate-specific antigen (PSA) levels between 20 and 100 ng/mL. less thanbrgreater than less thanbrgreater thanMaterials and Methods less thanbrgreater than less thanbrgreater thanPatients with PCa (T1-4, N0/N1/NX, M0/MX), PSA 20-100 ng/mL and age andlt;= 75 years were identified in the National Prostate Cancer Register of Sweden. less thanbrgreater than less thanbrgreater thanData on co-morbidity diagnoses were obtained from the National Patient Register and cause of death from the Cause of Death Register. less thanbrgreater than less thanbrgreater thanFollowing adjustment for age at diagnosis, co-morbidity burden, Gleason score, T-category, PSA level and cause-specific mortality in relation to treatment were estimated using Cox regression analysis. less thanbrgreater than less thanbrgreater thanResult less thanbrgreater than less thanbrgreater thanA total of 11 380 men were diagnosed with PCa between 1996 and 2008 and fulfilled the inclusion criteria. less thanbrgreater than less thanbrgreater thanThe cumulative 10-year PCa-specific mortality was 36% for patients receiving only palliative treatment and 13% for those treated with curative intent. less thanbrgreater than less thanbrgreater thanFor the 8462 (74%) patients with PSA levels from 20 to 50 ng/mL at diagnosis, the hazard ratio for death from PCa was 0.23 (95% confidence interval 0.19-0.27) for those treated with curative intent compared with those given palliative treatment after adjusting for age, co-morbidity, T category, PSA level and Gleason score. The corresponding hazard ratio was 0.22 (95% confidence interval 0.17-0.30) for patients with PSA levels from 51 to 100 ng/mL. less thanbrgreater than less thanbrgreater thanConclusion less thanbrgreater than less thanbrgreater thanTreatment with curative intent for men with high-risk PCa was associated with reduced cause-specific mortality and should be considered even when serum PSA exceeds 20 ng/mL. Keywords prostate cancer, prostate-specific antigen, high-risk tumours, curative treatment, palliative treatment, population-based study
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| 13. |
- Ladjevardi, Sam, et al.
(author)
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Tumour Grade, Treatment, and Relative Survival in a Population-based Cohort of Men with Potentially Curable Prostate Cancer
- 2010
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 57:4, s. 631-638
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Journal article (peer-reviewed)abstract
- Background: There is insufficient information regarding the benefit of treatment with curative intent for men with localised poorly differentiated prostate cancer (PCa). Objective: To evaluate relative survival in men with potentially curable PCa in relation to Gleason score (GS) and treatment as practiced in the community at large. Design, setting, and participants: A population-based study including all men with localised PCa registered in Sweden's National Prostate Cancer Register. Interventions: Hormonal therapy, watchful waiting, and treatment with curative intent. Measurements: The ratio of observed deaths to expected deaths, determined from survival in the general male population of the same age, was assessed using Poisson regression analysis, with GS and treatment as covariates. Interaction between GS and treatment was tested in a multivariate Cox proportional hazard analysis. Results and limitations: A total of 31 903 men with potentially curable tumour (T1-T3, N0/NX, M0/MX, age < 75 yr, and prostate-specific antigen [PSA] < 20 ng/ml) were identified. GS was recorded for 28 454 of these men. Some 19 606 men (60.8%) were treated with curative intent, and 12 645 men (39.2%) were given either hormonal treatment or expectant management. The ratios between observed and expected survival gradually increased for men with GS 10, with GS to 3.3 for men treated conservatively and to 1.4 for men treated with curative intent. There was a significant interaction between GS and treatment, with a relatively greater benefit from treatment with curative intent for men with high-grade tumours. The results have to be interpreted with some caution, as there was no randomisation between the treatment groups. Conclusions: Survival for men with well-differentiated tumours is close to that of the general population, regardless of treatment, but the outcome is dismal for men with poorly differentiated tumours, whichever treatment is applied. Nevertheless, men with poorly differentiated tumours benefit more from curative treatment than do men with well-differentiated tumours.
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| 14. |
- Regula, Naresh, et al.
(author)
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Carbon Flux as a Measure of Prostate Cancer Aggressiveness : [11C]-Acetate PET/CT
- 2020
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In: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 17:2, s. 214-223
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Journal article (peer-reviewed)abstract
- Purpose: Dynamic [11C]-acetate positron emission tomography (PET) can be used to study tissue perfusion and carbon flux simultaneously. In this study, the feasibility of the quantification of prostate cancer aggressiveness using parametric methods assessing [11C]-acetate kinetics was investigated in prostate cancer subjects. The underlying uptake mechanism correlated with [11C]-acetate influx and efflux measured in real-time in vitro in cell culture.Methods: Twenty-one patients with newly diagnosed low-to-moderate risk prostate cancer underwent magnetic resonance imaging (MRI) and dynamic [11C]-acetate PET/CT examinations of the pelvis. Parametric images of K1 (extraction × perfusion), k2 (oxidative metabolism) and VT (=K1/k2, anabolic metabolism defined as carbon retention) were constructed using a one-tissue compartment model with an arterial input function derived from pelvic arteries. Regions of interest (ROIs) of the largest cancer lesion in each patient and normal prostate tissue were drawn using information from MRI (T2 and DWI images), biopsy results, and post-surgical histopathology of whole prostate sections (n=7). In vitro kinetics of [11C]-acetate were studied on DU145 andPC3 cell lines using LigandTracer® White equipment for the measurement of the radioactivity uptake in real-time at 37°C.Results: Mean prostate specific antigen (PSA) was 8.33±3.92 ng/mL and median Gleason Sum 6 (range 5-7). K1,VT and standardized uptake values (SUVs) were significantly higher in cancerous prostate tissues compared to normal ones for all patients (p<0.001), while k2 was not (p=0.26). PSA values correlated to early SUVs (r=0.50,p=0.02) and K1 (r=0.48, p=0.03). Early and late SUVs correlated to VT (r>0.76, p<0.001) and K1 (r>0.64,p<0.005). In vitro studies demonstrated higher extraction and retention (p<0.01) of [11C]-acetate in the more aggressive PC3 cells.Conclusion: Parametric images could be used to visualize the [11C]-acetate kinetics of the prostate cancer exhibiting elevated extraction associated with the cancer aggressiveness. The influx rate of [11C]-acetate studied in cell culture also showed dependence on the cancer aggressiveness associated with elevated lipogenesis. Dynamic [11C]-acetate/PET demonstrated potential for prostate cancer aggressiveness estimation using parametric-based K1 and VT values.
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| 15. |
- Regula, Naresh Kumar, et al.
(author)
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Dynamic Imaging of Prostate Cancer with 11C-acetate PET/CT
- 2017
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In: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 58:S1
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Journal article (other academic/artistic)abstract
- Objectives: Dynamic 11C-acetate PET/CT can be used to study tissue perfusion and carbon flux simultaneously, but studies in cancer are limited. We investigated the kinetics of 11C-acetate in prostate cancer subjects using parametric images with an image-derived input function (IDIF).Methods: Twenty-one patients with newly diagnosed low-moderate risk prostate cancer were studied. All underwent pelvic MRI. Dynamic 11C-acetate (5 MBq/kg) PET/CT of the pelvis was acquired for 32 minutes with 32 time frames. An IDIF was acquired from iliac vessels with multiple small regions of interest (ROIs) and a standardized metabolite correction. Parametric images of K1 (extraction), k2 (oxidative metabolism) and Vd (=K1/k2, anabolic metabolism defined as carbon retention) were constructed using a one-tissue compartment model. ROIs of the largest cancer region in each patient and normal prostate tissue were drawn using information from MRI (T2 and DWI images) and from post-surgical histopathology of whole prostate sections (n=7).Results: Mean PSA was 8.3±3.9. Median Gleason Sum was 6 (range 5-7). K1, Vd and SUVs were higher in cancerous regions compared to normal prostate for all patients (p<0.001). PSA correlated to early SUV (r=0.50, p=0.02) and K1 (r=0.48, p=0.03). Early and late SUVs were correlated to Vd (r>0.76, p<0.001) and K1 (r>0.61, p<0.005).Conclusion: Parametric images could be used to visualize the 11C-acetate kinetics of the prostate. In this cohort of relatively low-risk cancers, PSA values were related to cancer perfusion. SUV of cancerous regions at any time point is primarily associated with anabolic metabolism. Research Support: Swedish Cancer Foundation (Cancerfonden)
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| 16. |
- Röbeck, Pontus, et al.
(author)
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Multiplex protein analysis and ensemble machine learning methods of fine needle aspirates from prostate cancer patients reveal potential diagnostic signatures associated with tumour grade
- 2023
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In: Cytopathology. - : Wiley. - 0956-5507 .- 1365-2303. ; 34:4, s. 286-294
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Journal article (peer-reviewed)abstract
- Background: Improved molecular diagnosis is needed in prostate cancer (PC). Fine needle aspiration (FNA) is a minimally invasive biopsy technique, less traumatic compared to core needle biopsy, and could be useful for diagnosis of PC. Molecular biomarkers (BMs) in FNA-samples can be assessed for prediction, eg of immunotherapy efficacy before treatment as well as at treatment decision time points during disease progression.Methods: In the present pilot study, the expression levels of 151 BM proteins were analysed by proximity extension assay in FNA-samples from 16 patients, including benign prostate lesions (n = 3) and cancers (n = 13). An ensemble data analysis strategy was applied using several machine learning models.Results: Twelve potentially predictive BM proteins correlating with International Society of Urological Pathology grade groups were identified, among them vimentin, tissue factor pathway inhibitor 2, and integrin beta-5. The validity of the results was supported by network analysis that showed functional associations between most of the identified putative BMs. We also showed that multiple immune checkpoint targets can be assessed (eg PD-L1, CD137, and Galectin-9), which may support the selection of immunotherapy in advanced PC. Results are promising but need further validation in a larger cohort.Conclusions: Our pilot study represents a “proof of concept” and shows that multiplex profiling of potential diagnostic and predictive BM proteins is feasible on tumour material obtained by FNA sampling of prostate cancer. Moreover, our results demonstrate that an ensemble data analysis strategy may facilitate the identification of BM signatures in pilot studies when the patient cohort is limited.
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| 17. |
- Röbeck, Pontus, et al.
(author)
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P-score in preoperative biopsies accurately predicts P-score in final pathology at radical prostatectomy in patients with localized prostate cancer
- 2023
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In: The Prostate. - : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 83:9, s. 831-839
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Journal article (peer-reviewed)abstract
- BACKGROUND: Prostate cancer (PCa) is a highly heterogeneous, multifocal disease, and identification of clinically significant lesions is challenging, which complicates the choice of adequate treatment. The Prostatype® score (P-score) is intended to guide treatment decisions for newly diagnosed PCa patients based on a three-gene signature (IGFBP3, F3, and VGLL3) and clinicopathological information obtained at diagnosis. This study evaluated association of the P-score measured in preoperative magnetic resonance imaging/transrectal ultrasound fusion-guided core needle biopsies (CNBs) and the P-score measured in radical prostatectomy (RP) specimens of PCa patients. We also evaluated the P-score association with the pathology of RP specimens. Furthermore, concordance of the P-score in paired CNB and RP specimens, as well as in index versus concomitant nonindex tumor foci from the same RP was investigated.METHODS: The study included 100 patients with localized PCa. All patients were diagnosed by CNB and underwent RP between 2015 and 2018. Gene expression was assessed with the Prostatype® real-time quantitative polymerase chain reaction kit and the P-score was calculated. Patients were categorized into three P-score risk groups according to previously defined cutoffs.RESULTS: For 71 patients, sufficient CNB tumor material was available for comparison with the RP specimens. The CNB-based P-score was associated with the pathological T-stage in RP specimens (p = 0.02). Moreover, the CNB-based P-score groups were in substantial agreement with the RP-based P-score groups (weighted κ score: 0.76 [95% confidence interval, 95% CI: 0.60-0.92]; Spearman's rank correlation coefficient r = 0.83 [95% CI: 0.74-0.89]; p < 0.0001). Similarly, the P-score groups based on paired index tumor and concomitant nonindex tumor foci (n = 64) were also in substantial agreement (weighted κ score: 0.74 [95% CI: 0.57-0.91]; r = 0.83 [95% CI: 0.73-0.89], p < 0.0001).CONCLUSIONS: Our findings suggest that the P-score based on preoperative CNB accurately reflects the pathology of the whole tumor, highlighting its value as a decision support tool for newly diagnosed PCa patients.
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| 18. |
- Sandblom, Gabriel, et al.
(author)
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The impact of prostate-specific antigen level at diagnosis on the relative survival of 28,531 men with localized carcinoma of the prostate
- 2008
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In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 112:4, s. 813-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: To evaluate the predictive value of prostate-specific antigen (PSA) in a population-based cohort, the authors analyzed relative survival in all men with localized prostate cancer who were registered in the Swedish National Prostate Cancer Register (NPCR) from 1996 to 2005. METHODS: All men aged <75 years with localized tumors were identified in the NPCR. A Poisson regression analysis was performed using observed death as response and the expected death rate as offset. The expected and observed numbers of survivors were calculated with stratification for PSA level and 3 categories of tumor differentiation (Gleason score 2-6, 7, and 8-10). The regression model included PSA as linear splines with a breakpoint at a PSA level of 4 ng/mL and with tumor differentiation as a categoric variable. RESULTS: The Poisson regression analysis indicated a U-shaped curve for all 3 groups, with a negative correlation between PSA and relative survival in men with PSA levels <4 ng/mL and a positive correlation for men with PSA levels >4 ng/mL. The correlation was significant for all 3 groups, but the negative correlation between PSA and relative survival was significantly more pronounced in the group with Gleason scores from 8 to 10 than in the other 2 Gleason score groups. CONCLUSIONS: The demonstration of an inverse correlation between PSA level and relative survival in the group of men with PSA levels <4 ng/mL indicated the presence of a small but clinically important subgroup with undifferentiated tumors who have cells that have lost the ability to secrete PSA. This group should be taken into consideration when deciding on treatment and when choosing a cutoff level in PSA screening programs.
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| 19. |
- Tammela, T L, et al.
(author)
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An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer
- 2017
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In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 198:6, s. 1333-1339
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Journal article (peer-reviewed)abstract
- PURPOSE: To investigate tolerability, safety and antitumor effects of a novel intra-prostatic depot formulation of antiandrogen 2-hydroxyflutamide (2-HOF in NanoZolid(®)) in men with localized prostate cancer (PCa).MATERIALS AND METHODS: Two clinical trials, LPC-002 and LPC-003, were conducted on a total of 47 men. The formulation was injected transrectally into the prostate with ultrasound guidance. In LPC-002 the effects on prostate specific antigen (PSA) and prostate volume (PV) were measured over 6 months on 24 patients. In LPC-003, antitumor effects were evaluated with histopathology, magnetic resonance imaging (MRI) including spectroscopy (MRS) during 6 or 8 weeks on 23 patients. In both studies, testosterone and 2-HOF in plasma were measured, as well as quality-of-life parameters.RESULTS: In LPC-002 (mean dose 690 mg) a reduction in PSA and PV was observed. The nadir values for PSA and PV were on average 24.9 % and 14.0 % below baseline, respectively. When increasing the dose in LPC-003 (920 mg and 1740 mg), the average PSA dropped 16 % and 23 %, respectively, after 6 and 8 weeks. MRI/MRS showed morphological changes and a global drop in metabolite concentrations following treatment indicating an antitumor response. The injections did not result in hormone related side effects. In total, three serious adverse events were reported, all resolved by oral antibiotic treatment.CONCLUSIONS: The intraprostatic injections of 2-HOF depot formulations indicated anti-tumor effects and proved safe and tolerable. However, for better anti-cancer effects higher doses and better dose distribution are suggested.
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| 20. |
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| 21. |
- von Below, Catrin, 1970-, et al.
(author)
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Additional value of magnetic resonance-targeted biopsies to standard transrectal ultrasound-guided biopsies for detection of clinically significant prostate cancer
- 2017
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In: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 51:2, s. 107-113
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim of this study was to evaluate the additional value of magnetic resonance imaging-targeted biopsy (MRI-TB) to standard transrectal ultrasound-guided biopsy (SB) for detection of clinically significant prostate cancer (PCa). An additional aim was to compare the biopsy results to MRI evaluation using a Likert scale.MATERIALS AND METHODS: Patients with newly diagnosed localized PCa (n = 53) by clinical routine SB were prospectively included. The majority of the patients were scheduled for curative therapy before enrollment. The patients underwent multiparametric MRI (mpMRI) at 3 T using an endorectal coil followed by two MRI-TBs, using ultrasound with cognitive fusion. All included patients underwent MRI-TB, even those who had low to very low suspicion of significant PCa on mpMRI. The detection rate of significant cancer on SB versus SB + MRI-TB was compared in the 53 included patients and with whole-mounted histopathology as reference in 34 cases. Comparison of the biopsy results to MRI evaluation and interreader agreement calculation of five-point Likert score evaluation were performed.RESULTS: In total, 32 significant (Gleason ≥7) PCa were detected by SB, while SB + MRI-TB detected an additional five significant PCa. MRI-TB alone detected 20 and missed 17 significant PCa. Ten of the significant PCa cases missed by MRI-TB had a Likert score of 3 or lower. Interreader agreement using the Likert scale was high, with a kappa value of 0.77 (95% confidence interval 0.63-0.92, p < 0.0001).CONCLUSION: Detection of significant PCa increased by adding MRI-TB to SB. This may not be of enough clinical value to justify the use of targeted biopsies in this patient group.
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- Weis, Jan, 1956-, et al.
(author)
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Quantification of metabolite concentrations in benign and malignant prostate tissues using 3D proton MR spectroscopic imaging
- 2017
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In: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 45:4, s. 1232-1240
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Journal article (peer-reviewed)abstract
- PURPOSE: To estimate concentrations of choline (Cho), spermine (Spm), and citrate (Cit) in prostate tissue using 3D proton magnetic resonance spectroscopic imaging (MRSI) with water as an internal concentration reference as well as to assess the relationships between the measured metabolites and also between the metabolites and apparent diffusion coefficient (ADC).MATERIALS AND METHODS: Forty-six prostate cancer patients were scanned at 3T. Spectra were acquired with the point-resolved spectroscopy (PRESS) localization technique. Single-voxel spectra of four healthy volunteers were used to estimate T1 relaxation time of Spm. Spm, Cho concentrations, and ADC values of benign prostate tissues were correlated with Cit content.RESULTS: The T1 value, 708 ± 132 msec, was estimated for Spm. Mean concentrations in the benign peripheral zone (PZ) were Cho, 4.5 ± 1 mM, Spm, 13.0 ± 4.4 mM, Cit, 64.4 ± 16.1 mM. Corresponding values in the benign central gland (CG) were Cho, 3.6 ± 1 mM, Spm, 13.3 ± 4.5 mM, Cit, 34.3 ± 12.9 mM. Concentrations of Cit and Spm were positively correlated in the benign PZ zone (r = 0.730) and CG (r = 0.664). Positive correlation was found between Cit and Cho in the benign CG (r = 0.705). Whereas Cit and ADC were positively correlated in the benign PZ (r = 0.673), only low correlation was found in CG (r = 0.265).CONCLUSION: We have shown that it is possible to perform water-referenced quantitative 3D MRSI of the prostate at the cost of a relatively short prolongation of the acquisition time. The individual metabolite concentrations provide additional information compared to the previously used metabolite-to-citrate ratios.
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