| 1. |
- Grefve, Josefine, et al.
(författare)
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Histopathology-validated gross tumor volume delineations of intraprostatic lesions using PSMA-positron emission tomography/multiparametric magnetic resonance imaging
- 2024
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Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Dose escalation in external radiotherapy of prostate cancer shows promising results in terms of biochemical disease-free survival. Boost volume delineation guidelines are sparse which may cause high interobserver variability. The aim of this research was to characterize gross tumor volume (GTV) delineations based on multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen-positron emission tomography (PSMA-PET) in relation to histopathology-validated Gleason grade 4 and 5 regions.Material and methods: The study participants were examined with [68Ga]PSMA-PET/mpMRI prior to radical prostatectomy. Four radiation oncologists delineated GTVs in 15 study participants, on four different image types; T2-weighted (T2w), diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) and PSMA-PET scans separately. The simultaneous truth and performance level estimation (STAPLE) algorithm was used to generate combined GTVs. GTVs were subsequently compared to histopathology. We analysed how Dice similarity coefficient (DSC) and lesion coverage are affected by using single versus multiple image types as well as by adding a clinical target volume (CTV) margin.Results: Median DSC (STAPLE) for different GTVs varied between 0.33 and 0.52. GTVPSMA-PET/mpMRI generated the highest median lesion coverage at 0.66. Combining different image types achieved similar lesion coverage as adding a CTV margin to contours from a single image type, while reducing non-malignant tissue inclusion within the target volume.Conclusion: The combined use of mpMRI or PSMA-PET/mpMRI shows promise, achieving higher DSC and lesion coverage while minimizing non-malignant tissue inclusion, in comparison to the use of a single image type with an added CTV margin.
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| 2. |
- Strömberg, Ulf, 1964, et al.
(författare)
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Socioeconomic inequality in prostate cancer diagnostics, primary treatment, rehabilitation, and mortality in Sweden
- 2024
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Ingår i: INTERNATIONAL JOURNAL OF CANCER. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 155:4, s. 637-645
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Tidskriftsartikel (refereegranskat)abstract
- We designed a nationwide study to investigate the association between socioeconomic factors (household income and education) and different aspects of prostate cancer care, considering both individual- and neighbourhood-level variables. Data were obtained from Prostate Cancer data Base Sweden (PCBaSe), a research database with data from several national health care registers including clinical characteristics and treatments for nearly all men diagnosed with prostate cancer in Sweden. Four outcomes were analysed: use of pre-biopsy magnetic resonance imaging (MRI) in 2018-2020 (n = 11,843), primary treatment of high-risk non-metastatic disease in 2016-2020 (n = 6633), rehabilitation (>= 2 dispensed prescriptions for erectile dysfunction within 1 year from surgery in 2016-2020, n = 6505), and prostate cancer death in 7770 men with high-risk non-metastatic disease diagnosed in 2010-2016. Unadjusted and adjusted odds and hazard ratios (OR/HRs) with 95% confidence intervals (CIs) were calculated. Adjusted odds ratio (ORs) comparing low versus high individual education were 0.74 (95% CI 0.66-0.83) for pre-biopsy MRI, 0.66 (0.54-0.81) for primary treatment, and 0.82 (0.69-0.97) for rehabilitation. HR gradients for prostate cancer death were significant on unadjusted analysis only (low vs. high individual education HR 1.41, 95% CI 1.17-1.70); co-variate adjustments markedly attenuated the gradients (low vs. high individual education HR 1.10, 95% CI 0.90-1.35). Generally, neighbourhood-level analyses showed weaker gradients over the socioeconomic strata, except for pre-biopsy MRI. Socioeconomic factors influenced how men were diagnosed with prostate cancer in Sweden but had less influence on subsequent specialist care. Neighbourhood-level socioeconomic data are more useful for evaluating inequality in diagnostics than in later specialist care.
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| 3. |
- Tegenborg, Sussi, 1968-
(författare)
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Pain or no pain? That is the question : an evaluation of the observational pain assessment instrument Abbey Pain Scale in patients with cancer
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The Abbey Pain Scale (APS) is an observational pain assessment instrument that was created for use among patients with dementia. It is sometimes used in Sweden to assess pain in patients with advanced cancer who are unable to vocalize their pain, but it has never been evaluated in this population.Aim: To evaluate observational pain assessment for people with advanced cancer in a palliative care setting, focusing on the APS.Methods: The APS was translated and adapted into a Swedish dementia context through interviews with health care professionals (n=11). The resulting APS-SE was then used in a qualitative content analysis exploring health care professionals’ experience of using the instrument in patients with advanced cancer (n=12). The psychometrics of the APS-SE when used in patients with advanced cancer (n=72) were determined through test-retest and inter-rater reliability, internal consistency reliability, and responsiveness to opioids. Criterion validity was determined against the patients’ self-reported pain (n=45).Results: The APS-SE was comprehensible by users within dementia care, regardless of their educational and linguistic background. The qualitative analysis revealed that when used in patients with advanced cancer, the APS-SE fulfilled the need for an observational pain assessment instrument, but was not always on target and did not fully suit the clinical situation. The psychometric analysis showed slight criterion validity (κ=0.08) and unacceptable internal consistency reliability (Cronbach’s α=0.01). The test-retest reliability was good (ICC=0.82) and the inter-rater reliability moderate (ICC=0.64), but the latter had a confidence interval ranging from poor to good. Responsiveness to opioids was demonstrated (p=0.01).Conclusions: This thesis underscores the need for a specialized observational pain assessment instrument explicitly tailored for patients with advanced cancer. The current lack of a recognized alternative emphasizes the importance of developing such an instrument to address the critical gap in observational pain assessment in the palliative oncology setting.
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| 4. |
- Zarei, Maryam, et al.
(författare)
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Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer
- 2024
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Ingår i: Acta Oncologica. - : MJS Publishing, Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 503-510
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.MATERIALS AND METHODS: The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold.RESULTS: The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm.INTERPRETATION: Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.
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| 5. |
- Björeland, Ulrika, et al.
(författare)
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Hyaluronic acid spacer in prostate cancer radiotherapy : dosimetric effects, spacer stability and long-term toxicity and PRO in a phase II study
- 2023
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Ingår i: Radiation Oncology. - : BioMed Central (BMC). - 1748-717X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Perirectal spacers may be beneficial to reduce rectal side effects from radiotherapy (RT). Here, we present the impact of a hyaluronic acid (HA) perirectal spacer on rectal dose as well as spacer stability, long-term gastrointestinal (GI) and genitourinary (GU) toxicity and patient-reported outcome (PRO).METHODS: In this phase II study 81 patients with low- and intermediate-risk prostate cancer received transrectal injections with HA before external beam RT (78 Gy in 39 fractions). The HA spacer was evaluated with MRI four times; before (MR0) and after HA-injection (MR1), at the middle (MR2) and at the end (MR3) of RT. GI and GU toxicity was assessed by physician for up to five years according to the RTOG scale. PROs were collected using the Swedish National Prostate Cancer Registry and Prostate cancer symptom scale questionnaires.RESULTS: There was a significant reduction in rectal V70% (54.6 Gy) and V90% (70.2 Gy) between MR0 and MR1, as well as between MR0 to MR2 and MR3. From MR1 to MR2/MR3, HA thickness decreased with 28%/32% and CTV-rectum space with 19%/17% in the middle level. The cumulative late grade ≥ 2 GI toxicity at 5 years was 5% and the proportion of PRO moderate or severe overall bowel problems at 5 years follow-up was 12%. Cumulative late grade ≥ 2 GU toxicity at 5 years was 12% and moderate or severe overall urinary problems at 5 years were 10%.CONCLUSION: We show that the HA spacer reduced rectal dose and long-term toxicity.
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| 6. |
- Björeland, Ulrika, 1974-
(författare)
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MRI in prostate cancer : implications for target volume
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer (PCa) is the most common cancer among men, with 10 000 new cases per year in Sweden [1]. To diagnose PCa, magnetic resonance imaging (MRI) is used to identify and classify the disease. The patient’s treatment strategy depends on PCa classification and clinical data, which are weighted together into a risk group classification from 1–5. For patients with higher risk classes (>3), radiotherapy together with hormone therapy is a common treatment option [2].In radiotherapy (RT), individual treatment plans are created based on the patient’s anatomy. These plans are based on computed tomography (CT), often supplemented with MRI images. MRI and CT complement each other, as MRI has better soft tissue contrast and CT has better bone contrast. Based on the images, the volumes to be treated (target) and the volumes to be avoided (risk organs) are defined. Prostate RT is complex, and there are uncertainties regarding the patient's internal movements and how the patient is positioned before each treatment. To account for these uncertainties, the radiation field is expanded (extended margins to target) to ensure that the treatment volume receives its radiotherapy. RT is most often given in fractions. Fractionation, dose, and treatment volume depend on the patient’s risk category. The treatment area can be, for example, only prostate, prostate with extra radiation dose (boost) to an intraprostatic tumour, or prostate with lymph node (LN) irradiation. LN irradiation is most often given for preventive purposes for PCa with a risk classification >4, which means no cancer has been identified, but any microscopic spread to the LNs is being treated profylactically.In RT, target identification is essential both in the treatment planning images (CT/MRI) and at treatment. Studies have shown that PCa often re-occurs in or near the volume of the dominant (often largest) intraprostatic tumour [3, 4], and this volume is relevant for boosting. For patients treated with hormone therapy before radiotherapy, tumour identification is complicated. Hormones change the tumour characteristics, affecting the image contrast and making the tumour difficult to identify. To study this, we investigated whether texture analysis could identify the tumour volume after hormone therapy (paper II). However, even with texture analysis, the tumour was difficult to identify. A follow-up study examined whether the image information in MRI images taken before hormone therapy could indicate how the treatment fell out (paper IV). However, no correlation was seen between image features and the progression of PCa.Identifying the target and correctly positioning the patient for each treatment fraction is the most important procedure in radiotherapy. The prostate is a mobile organ; therefore, intraprostatic fiducial markers are inserted before treatment planning to reduce positioning uncertainties. Each radiotherapy session begins with an X-ray image where the markers are visible, and the radiation can be delivered based on the markers' position. The markers are also used as guidance for large target volumes, such as for prostate with LN irradiation. With better knowledge of the prostate and LN movements, the margins can potentially be reduced, followed by reduced radiation dose to healthy tissue and therefore reduced side effects for patients. Movements in the radiotherapy volume were the focus of paper I. Using MRI images, the movements of the prostate and LNs were measured during the course of radiotherapy, and we found that LN movement is independent of the movement of the prostate and that the movement varies in the target volume.In addition to the recurrence of PCa in the tumour area, there is an increased risk of recurrence in the prostate periphery close to the rectum. Since the rectum and prostate are in contact for some patients, RT must be adapted to make rectum side effects tolerable. One way to increase the distance between the prostate and the rectum is to inject a gel between the two organs. The distance makes it easier to achieve a better dose distribution to the PCa. This idea resulted in paper III, where patients were given a gel between the prostate and rectum. MRI was used to check the stability of the gel during the course of RT and was evaluated together with long-term follow-up of the patient’s well-being and acceptance of the gel. We found that the radiation dose to the rectum was lower with a spacer, although the spacer was not completely stable during treatment.
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| 7. |
- Gedeborg, Rolf, et al.
(författare)
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Uptake of doublet therapy for de novo metastatic castration sensitive prostate cancer : a population-based drug utilisation study in Sweden
- 2023
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden. - 2168-1805 .- 2168-1813. ; 58, s. 93-100
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Tidskriftsartikel (refereegranskat)abstract
- Background: Randomised controlled trials have demonstrated prolonged survival with new upfront treatments in addition to standard androgen deprivation therapy (ADT) in men with de novo metastatic castration-sensitive prostate cancer. We describe patient characteristics, time trends and regional differences in uptake of these new treatment strategies in clinical practice.Material and methods: This descriptive study consisted of men registered in the National Prostate Cancer Register of Sweden from 1 January 2018 to 31 March 2022 with de novo metastatic castration-sensitive prostate cancer defined by the presence of metastases on imaging at the time of diagnosis. Life expectancy was calculated based on age, Charlson Comorbidity Index and a Drug Comorbidity Index.Results: Within 6 months from diagnosis, 57% (1,677/2,959) of men with de novo metastatic castration-sensitive prostate cancer and more than 3 years of life expectancy had received docetaxel, abiraterone, enzalutamide, apalutamide and/or radiotherapy. Over time, there was a 2-fold increase in uptake of any added treatment, mainly driven by a 6-fold increase in use of abiraterone, enzalutamide or apalutamide, with little change in use of other treatments.Conclusions: Slightly more than half of men diagnosed with de novo metastatic castration-sensitive prostate cancer and a life expectancy of at least 3 years received additions to standard ADT as recommended by national guidelines in 2019-2022 in Sweden. There was a 2-fold increase in use of these treatments during the study period; however, efforts to further increase adherence to guidelines are warranted.
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| 8. |
- Nilsson, Erik, et al.
(författare)
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The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography
- 2023
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Ingår i: Communications Medicine. - : Springer Nature. - 2730-664X. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET) are widely used for the management of prostate cancer (PCa). However, how these modalities complement each other in PCa risk stratification is still largely unknown. We aim to provide insights into the potential of mpMRI and PET for PCa risk stratification.Methods: We analyzed data from 55 consecutive patients with elevated prostate-specific antigen and biopsy-proven PCa enrolled in a prospective study between December 2016 and December 2019. [68Ga]PSMA-11 PET (PSMA-PET), [11C]Acetate PET (Acetate-PET) and mpMRI were co-registered with whole-mount histopathology. Lower- and higher-grade lesions were defined by International Society of Urological Pathology (ISUP) grade groups (IGG). We used PET and mpMRI data to differentiate between grades in two cases: IGG 3 vs. IGG 2 (case 1) and IGG ≥ 3 vs. IGG ≤ 2 (case 2). The performance was evaluated by receiver operating characteristic (ROC) analysis.Results: We find that the maximum standardized uptake value (SUVmax) for PSMA-PET achieves the highest area under the ROC curve (AUC), with AUCs of 0.72 (case 1) and 0.79 (case 2). Combining the volume transfer constant, apparent diffusion coefficient and T2-weighted images (each normalized to non-malignant prostatic tissue) results in AUCs of 0.70 (case 1) and 0.70 (case 2). Adding PSMA-SUVmax increases the AUCs by 0.09 (p < 0.01) and 0.12 (p < 0.01), respectively.Conclusions: By co-registering whole-mount histopathology and in-vivo imaging we show that mpMRI and PET can distinguish between lower- and higher-grade prostate cancer, using partially discriminative cut-off values.
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| 9. |
- Sandgren, Kristina, et al.
(författare)
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Histopathology-validated lesion detection rates of clinically significant prostate cancer with mpMRI, [68Ga]PSMA-11-PET and [11C]Acetate-PET
- 2023
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Ingår i: Nuclear medicine communications. - : Lippincott Williams & Wilkins. - 0143-3636 .- 1473-5628. ; 44:11, s. 997-1004
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Tidskriftsartikel (refereegranskat)abstract
- Objective: PET/CT and multiparametric MRI (mpMRI) are important diagnostic tools in clinically significant prostate cancer (csPC). The aim of this study was to compare csPC detection rates with [68Ga]PSMA-11-PET (PSMA)-PET, [11C] Acetate (ACE)-PET, and mpMRI with histopathology as reference, to identify the most suitable imaging modalities for subsequent hybrid imaging. An additional aim was to compare inter-reader variability to assess reproducibility.Methods: During 2016–2019, all study participants were examined with PSMA-PET/mpMRI and ACE-PET/CT prior to radical prostatectomy. PSMA-PET, ACE-PET and mpMRI were evaluated separately by two observers, and were compared with histopathology-defined csPC. Statistical analyses included two-sided McNemar test and index of specific agreement.Results: Fifty-five study participants were included, with 130 histopathological intraprostatic lesions >0.05 cc. Of these, 32% (42/130) were classified as csPC with ISUP grade ≥2 and volume >0.5 cc. PSMA-PET and mpMRI showed no difference in performance (P = 0.48), with mean csPC detection rate of 70% (29.5/42) and 74% (31/42), respectively, while with ACE-PET the mean csPC detection rate was 37% (15.5/42). Interobserver agreement was higher with PSMA-PET compared to mpMRI [79% (26/33) vs 67% (24/38)]. Including all detected lesions from each pair of observers, the detection rate increased to 90% (38/42) with mpMRI, and 79% (33/42) with PSMA-PET.Conclusion: PSMA-PET and mpMRI showed high csPC detection rates and superior performance compared to ACE-PET. The interobserver agreement indicates higher reproducibility with PSMA-PET. The combined result of all observers in both PSMA-PET and mpMRI showed the highest detection rate, suggesting an added value of a hybrid imaging approach.
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| 10. |
- Spyratou, Vasiliki, 1981, et al.
(författare)
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Ki67 and prostate specific antigen are prognostic in metastatic hormone naïve prostate cancer
- 2023
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:12, s. 1698-1706
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Tidskriftsartikel (refereegranskat)abstract
- Background: For metastatic hormone naïve prostate cancer patients, androgen deprivation therapy (ADT) with escalation therapy including docetaxel and/or androgen targeting drugs is the standard therapy. However, de-escalation is preferable to avoid unnecessary side effects, especially from docetaxel, but markers to identify these patients are lacking. The purpose of the present study was to investigate the potential of PSA and Ki67 immunoreactive scores as prognostic and treatment-predictive markers. Material and methods: Prostate biopsies from 92 patients with metastatic hormone naïve PC (PSA > 80 ng/mL or clinical metastases) were immunohistochemically evaluated for PSA and Ki67. Gene expression analysis was performed with Clariom D microarrays to identify the phenotypic profile associated with the immunohistochemistry scores of biopsies. Cox regression analysis for progression free survival after ADT adjustment for age, ISUP, and serum PSA and Kaplan-Meier analyses were performed to assess prognostic values of Ki67, PSA, and the Ki67/PSA ratio. Results: The immunohistochemical score for PSA was the strongest prognostic factor for progression-free and overall survival after ADT. Consequently, the ratio between Ki67 and PSA displayed a stronger prognostic value than Ki67 itself. Further, mRNA expression data analysis showed an association between high Ki67/PSA ratio, cell-cycle regulation, and DNA damage repair. In an exploratory sub-analysis of 12 patients treated with early docetaxel as addition to ADT and matched controls, a high Ki67/PSA ratio showed potential to identify those who benefit from docetaxel. Conclusion: PSA and Ki67 immunoreactive scores are prognostic in the metastatic hormone-sensitive setting, with PSA being superior. The combination of Ki67 and PSA did not give additional prognostic value. The results suggest immunohistochemical scoring of PSA to have potential to improve identification of patients responding well to ADT alone.
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