Immune-Activated B Cells Are Dominant in Prostate Cancer.

B cells are multifaceted immune cells responding robustly during immune surveillance against tumor antigens by presentation to T cells and switched immunoglobulin production. However, B cells are unstudied in prostate cancer (PCa). We used flow cytometry to analyze B-cell subpopulations in peripheral blood and lymph nodes from intermediate-high risk PCa patients. B-cell subpopulations were related to clinicopathological factors. B-cell-receptor single-cell sequencing and VDJ analysis identified clonal B-cell expansion in blood and lymph nodes. Pathological staging was pT2 in 16%, pT3a in 48%, and pT3b in 36%. Lymph node metastases occurred in 5/25 patients (20%). Compared to healthy donors, the peripheral blood CD19+ B-cell compartment was significantly decreased in PCa patients and dominated by naïve B cells. The nodal B-cell compartment had significantly increased fractions of CD19+ B cells and switched memory B cells. Plasmablasts were observed in tumor-draining sentinel lymph nodes (SNs). VDJ analysis revealed clonal expansion in lymph nodes. Thus, activated B cells are increased in SNs from PCa patients. The increased fraction of switched memory cells and plasmablasts together with the presence of clonally expanded B cells indicate tumor-specific T-cell-dependent responses from B cells, supporting an important role for B cells in the protection against tumors.

A Head-to-head Comparison of Prostate Cancer Diagnostic Strategies Using the Stockholm3 Test, Magnetic Resonance Imaging, and Swedish National Guidelines: Results from a Prospective Population-based Screening Study.

Background: Strategies for early detection of prostate cancer aim to detect clinically significant prostate cancer (csPCa) and avoid detection of insignificant cancers and unnecessary biopsies. Swedish national guidelines (SNGs), years 2019 and 2020, involve prostate-specific antigen (PSA) testing, clinical variables, and magnetic resonance imaging (MRI). The Stockholm3 test and MRI have been suggested to improve selection of men for prostate biopsy. Performance of SNGs compared with the Stockholm3 test or MRI in a screening setting is unclear. Objective: To compare strategies based on previous and current national guidelines, Stockholm3, and MRI to select patients for biopsy in a screening-by-invitation setting. Design setting and participants: All participants underwent PSA test, and men with PSA ≥3 ng/ml underwent Stockholm3 testing and MRI. Men with Stockholm3 ≥11%, Prostate Imaging Reporting and Data System score ≥3 on MRI, or indication according to SNG-2019 or SNG-2020 were referred to biopsy. Outcome measurements and statistical analysis: The primary outcome was the detection of csPCa at prostate biopsy, defined as an International Society of Urological Pathology (ISUP) grade of ≥2. Results and limitations: We invited 8764 men from the general population, 272 of whom had PSA ≥3 ng/ml. The median PSA was 4.1 (interquartile range: 3.4-5.8), and 136 of 270 (50%) who underwent MRI lacked any pathological lesions. In total, 37 csPCa cases were diagnosed. Using SNG-2019, 36 csPCa cases with a high biopsy rate (179 of 272) were detected and 49 were diagnosed with ISUP 1 cancers. The Stockholm3 strategy diagnosed 32 csPCa cases, with 89 biopsied and 27 ISUP 1 cancers. SNG-2020 detected 32 csPCa and 33 ISUP 1 cancer patients, with 99 men biopsied, and the MRI strategy detected 30 csPCa and 35 ISUP 1 cancer cases by biopsying 123 men. The latter two strategies generated more MRI scans than the Stockholm3 strategy (n = 270 vs 33). Conclusions: Previous guidelines provide high detection of significant cancer but at high biopsy rates and detection of insignificant cancer. The Stockholm3 test may improve diagnostic precision compared with the current guidelines or using only MRI. Patient summary: The Stockholm3 test facilitates detection of significant cancer, and reduces the number of biopsies and detection of insignificant cancer.

MRI and 11C Acetate PET/CT for Prediction of Regional Lymph Node Metastasis in Newly Diagnosed Prostate Cancer.

BACKGROUND: The aim of the study was to examine the value of quantitative and qualitative MRI and 11C acetate PET/CT parameters in predicting regional lymph node (LN) metastasis of newly diagnosed prostate cancer (PCa). PATIENTS AND METHODS: Patients with intermediate (n = 6) and high risk (n = 47) PCa underwent 3T MRI (40 patients) and 11C acetate PET/CT (53 patients) before extended pelvic LN dissection. For each patient the visually most suspicious LN was assessed for mean apparent diffusion coefficient (ADCmean), maximal standardized uptake value (SUVmax), size and shape and the primary tumour for T stage on MRI and ADCmean and SUVmax in the index lesion. The variables were analysed in simple and multiple logistic regression analysis. RESULTS: All variables, except ADCmean and SUVmax of the primary tumor, were independent predictors of LN metastasis. In multiple logistic regression analysis the best model was ADCmean in combintion with MRI T-stage where both were independent predictors of LN metastasis, this combination had an AUC of 0.81 which was higher than the AUC of 0.65 for LN ADCmean alone and the AUC of 0.69 for MRI T-stage alone. CONCLUSIONS: Several quantitative and qualitative imaging parameters are predictive of regional LN metastasis in PCa. The combination of ADCmean in lymph nodes and T-stage on MRI was the best model in multiple logistic regression with increased predictive value compared to lymph node ADCmean and T-stage on MRI alone.

Extended pelvic lymph-node dissection and radiotherapy with curative intent in high-risk lymph-node-positive prostate cancer: a possible curative strategy?

OBJECTIVE: This study evaluated the outcome with a treatment strategy for high-risk prostate cancer (PCa) using extended pelvic lymph-node dissection (eLND) followed by external beam radiation therapy (EBRT) in lymph-node-positive (LNpos) and lymph-node-negative (LNneg) cases compared with the strategy with limited pelvic lymph-node dissection (lLND) and only giving EBRT to LNneg cases. MATERIALS AND METHODS: From 2000 to 2006, 124 men with high-risk PCa underwent lLND and initiated androgen deprivation therapy (ADT) before planned EBRT. LNpos patients were excluded from EBRT following the SPCG-7 study strategy (group I). From 2007 to 2013, 111 patients underwent eLND and started ADT before EBRT, and LNneg and most LNpos patients received EBRT (group II). Using Kaplan-Meier plots and multivariable Cox regression, biochemical recurrence-free, metastasis-free, cancer-specific survival and overall survival were compared during a 10 year follow-up. RESULTS: PSA progression-free survival rates after 2, 4, 6, 8 and 10 years were 78%, 66%, 52%, 45% and 41% in group I, and 88%, 83%, 78%, 69% and 69% in group II (p < 0.001), respectively. Group II had a lower risk of PSA progression [hazard ratio (HR) = 0.43, 95% confidence interval (CI) 0.27,0.69, p = 0.001], metastasis development (HR = 0.51, 95% CI 0.27,0.97, p = 0.040) and overall mortality (HR = 0.49, 95% CI 0.26,0.92, p = 0.027), but not of PCa-specific death (HR = 0.45, 95% CI 0.19,1.08, p = 0.074). CONCLUSION: A treatment strategy for high-risk PCa with eLND combined with EBRT in LNneg and LNpos cases may improve outcome compared to a strategy with lLND and offering EBRT only to LNneg cases but ADT to LNpos cases.

Laparoscopic extended pelvic lymph node (LN) dissection as validation of the performance of [(11) C]-acetate positron emission tomography/computer tomography in the detection of LN metastasis in intermediate- and high-risk prostate cancer.

OBJECTIVES: To evaluate the accuracy of the radiopharmaceutical [(11) C]-acetate combined with positron emission tomography/computer tomography (acetate-PET/CT) in lymph node (LN) staging in newly diagnosed prostate cancer cases. A second aim was to evaluate the potential discriminative properties of acetate-PET/CT in clinical routine. PATIENTS AND METHODS: In a prospective comparative study, from July 2010 to June 2013, 53 men with newly histologically diagnosed intermediate- or high-risk prostate cancer underwent acetate-PET/CT investigation at one regional centre before laparoscopic extended pelvic LN dissection (ePLND) at one referral centre. The sensitivity, specificity and accuracy of acetate-PET/CT were calculated. Comparisons were made between true-positive and false-negative PET/CT cases to identify differences in the clinical parameters: PSA level, Gleason status, lymph metastasis burden and size, calculated risk of LN involvement, and curative treatment decisions. RESULTS: In all, 26 patients had surgically/histologically confirmed LN metastasis (LN+). Acetate-PET/CT was true positive in 10 patients, false positive in one, false negative in 16, and true negative in 26. The individual sensitivity was 38%, specificity 96%, and accuracy 68%. The acetate-PET/CT positive cases had significantly more involved LNs (mean 7.9 vs 2.4, P < 0.001) with larger cancer diameters (14.1 vs 4.9 mm, P = 0.001) and fewer eventually had treatment with curative intent (40% vs 94%, P <0.005), although we lack long-term outcome data. CONCLUSION: Acetate-PET/CT has too low a sensitivity for routine LN staging but the specificity is high. The acetate-PET/CT positive cases have a very high burden of LN spread.

A simple reconstruction of the posterior aspect of rhabdosphincter and sparing of puboprostatic collar reduces the time to early continence after laparoscopic radical prostatectomy.

BACKGROUND: Incontinence is a drawback after radical prostatectomy for prostate cancer. Several surgical methods to improve continence have been described however with contradictory results. OBJECTIVE: To determine whether a modified surgical technique during laparoscopic radical prostatectomy (LRP) improves postoperative continence. PATIENTS AND METHODS: This is a prospective nonrandomized study with two consecutive series of 100 patients in each group. The first group from 2005 to 2008 underwent a standard LRP. The second group from 2009 to 2011 was subjected to a modified LRP by sparing of puboprostatic ligaments, including the preservation of arcus tendineous, and using a simple posterior tension-releasing suture adapting the urethra stump to the bladder before the anastomosis. The patients had the same preoperative work-up and comparable preoperative baseline characteristics. The 2-year follow-up of the patients included a continence questionnaire and International Prostate Symptom Score (IPSS). Urinary peak flow (Qmax) and post-void residual (PVR) volume were assessed at 3 months. Continence was defined as 0-1 pad/day. RESULTS: Only 99 patients were evaluated in each group. The patients had comparable operative characteristics. The continence rates after the modified technique vs the standard were 33% vs 16%, p=0.007 at 1 month; 66% vs 44%, p=0.002 at 3 months; 81% vs 67%, p=0.034 at 6 months; 92% vs 80%, p=0.024 at 12 months; and 95% vs 86%, p=0.05 at 2 years. No significant differences were found regarding voiding functions, the Qmax, the PVR volume, or the IPSS. Three patients developed urethral stricture in the standard group compared with none in the modified group. The negative margin rates were unchanged. CONCLUSIONS: The anterior preservation and posterior suture technique studied is a simple, safe, and efficient method to shorten the time to continence after LRP without adverse effects on voiding or compromising the margin rates.

Quality of life in patients with skeletal metastases of prostate cancer and status prior to start of endocrine therapy: results from the Scandinavian Prostate Cancer Group Study 5.

OBJECTIVES: Prostate cancer (PC) is a highly lethal neoplastic disease affecting the physical, mental and social well-being of patients, i.e. their quality of life (QOL). Patients suffering from metastatic PC are faced with serious decisions regarding treatment strategies. Therefore, QOL information has become a crucial element of decision making in this group of patients. The first objective of this study was to describe QOL in a group of patients diagnosed with metastatic PC and skeletal metastases. At the time of evaluation the patients had not received any treatment but were evaluated before entering a study of androgen-modulating therapy (the Scandinavian Prostate Cancer Group study 5). The second objective was to identify demographic and disease-related factors affecting QOL. MATERIAL AND METHODS: A total of 917 patients with metastatic PC were evaluated using a well-described and validated questionnaire [European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30 (EORTC QLQ-C30)]. The characteristics of the PC were noted, and simultaneously patients were evaluated with respect to use of analgesics, pain and performance status using a scoring system. Biochemical tests were performed when patients entered the study. A multivariate regression analysis was performed to analyse the correlations between QOL scores, patient demographics and disease-related data. RESULTS: The patients reported QOL scores significantly lower than those in the background population. Pain and fatigue were pronounced, whereas dyspnoea, insomnia, loss of appetite, constipation and diarrhoea were less prominent. Patients with high tumour grades, high PSPA scores (the sum of the pain score, the performance status and the use of analgesics) and those using analgesics had significantly lower QOL scores than the other patients. CONCLUSIONS: Patients with metastatic PC have reduced QOL. Our findings are in line with those of other studies of QOL among patients with this disease as evaluated by means of the EORTC QLQ-C30 questionnaire. Baseline data from studies like this provide important information when treatment modalities for PC are evaluated.