Detecting prostate cancer metastases - PET/CT and the sentinel node technique

Prostate cancer is one of the most common malignancies. Its treatment is highly dependent on the presence or absence of metastases. The available invasive and non-invasive modalities for detecting metastases are imperfect. Positron-emission tomography fused with computed tomography (PET/CT) is a non-invasive method for detecting metastases that is presently evaluated for prostate cancer. Fluoride and choline are PET/CT tracers with different properties; fluoride detects bone metastases only, while choline may detect metastases in bone, lymph nodes, and other organs. Sentinel node (SN) detection is an invasive method that allows selective dissection of the lymph nodes most likely to contain metastases. The SN technique may increase the detection rate by identifying metastases also outside the template of a standard lymphadenectomy. The clinical implications of the combination of choline and fluoride PET/CT were prospectively evaluated in Study I. The findings of choline PET/CT were compared with extended pelvic lymph node dissection (ePLND) in Study II. The clinical implications of early choline PET/CT in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) was evaluated in Study III. SN detection was prospectively evaluated and compared with ePLND in Study IV. The main results were: 1) A fifth of patients with high-risk prostate cancer and normal or inconclusive planar bone scan had extensive metastatic findings on the PET/CT exams, leading to change of management. The choline and fluoride scans did on their own indicate metastases in patients in which the other scan did not. 2) Choline PET/CT had a high specificity (0.98) but, depending on the cut-off value of tracer uptake, had a low sensitivity (0.21–0.46) for lymph node metastases. 3) Choline PET/CT indicated metastases in 28% of hormone-naïve patients with BCR after RP and prostate-specific antigen of less than 2 ng/mL. 4) SN detection performed at least equal to ePLND in determining lymph node stage, with sensitivity 0.96. Conclusions: Choline and fluoride PET/CT and SN detection may be valuable diagnostic modalities for detecting metastases of prostate cancer

Laparoscopic extended pelvic lymphadenectomy for staging can be performed with limited morbidity and short hospital stay in patients with prostate cancer.

Objective: Assessing lymph-node status in prostate cancer patients with high accuracy is only possible with surgical staging, despite the evolution of modern imaging techniques. The use of surgical staging has to be balanced against the complications of the procedure, the individual patient's risk for harbouring metastasesand the consequences for the treatment of the patient if such metastases are present. The aim of this study was to investigate complications at 90 days using a standardized method (Clavien) in a consecutive series of patients submitted to laparoscopic extendedpelvic lymphadenectomy. Material and methods: This population-based study included 133 high-risk prostate cancer patients scheduled for external beam radiation. Laparoscopic extended pelvic lymphadenectomy and registration of complications wereperformed in a standardized fashion. Complications were registered on a five-grade scale, and differences between groups were compared with the chi-squared test. Results: The mean hospital stay was 1.3 days. Only three patients (2%) suffered from grade 3 complications after surgery, whereas 35 patients (26%) had grade 1 complications and another 11 patients (8%) were treated for grade 2 complications. Of all patients, 35% had lymph-node metastasis, of whom 50% received intensified oncological treatment including adjuvant androgen deprivation and regional lymph-node radiation. Thus, 65% of the patients could be spared regional lymph-node radiation and its associated long-term toxicity. Conclusions: Laparoscopic extended pelvic lymphadenectomy can be performed with minimal significant complications and short hospital stay in patients with high-risk prostate cancer

Shortened time to diagnosis for patients suspected of urinary bladder cancer managed in a standardized care pathway was associated with an improvement in tumour characteristics

Abstract Objectives To evaluate whether the implementation of standardized care pathway (SCP) for patients with suspected urinary bladder cancer (UBC) was associated with changes in tumour characteristics. Additionally, the study aims to explore whether there was a shift in the selection of patients prioritized for immediate evaluation regarding suspicion of UBC. Materials and Methods The study included all patients diagnosed with UBC in the NU Hospital Group between 2010 and 2019. To evaluate changes associated with SCP, patients were divided into two diagnostic time periods, either before (2010–2015) or during (2016–2019) the implementation of the SCP. To evaluate which patients were prioritized for prompt evaluation within 13 days, logistic regression analysis was performed on all patients before and during SCP. Results Median time to transurethral resection of the tumour in urinary bladder (TURBT) decreased from 29 days (interquartile range [IQR] 16–48) before SCP to 12 days (IQR 8–19) during SCP (p < 0.001) with a clear break from 2016. The proportion of cT2 + tumours decreased during SCP from 26% to 20% (p = 0.035). In addition, tumours detected during SCP were smaller (p = 0.023), but with more multiple lesions (p = 0.055) and G3 tumours (p = 0.007). During SCP, there was no statistically significant difference between the groups of patients with TURBT within or after 13 days. In contrast, before SCP, a majority of the patients treated within 13 days had advanced tumours and were admitted from the emergency ward. Conclusions The implementation of an SCP for suspected UBC was associated with improved tumour characteristics. Interestingly, during SCP, there were no substantial differences in patients' or tumours' characteristics among those who underwent TURBT within or after 13 days. This indicates that the 13‐day timeframe for TURBT might be prolonged, especially in less urgent cases in order to facilitate a prioritization of more severe cases with treatable disease

A population-based study of the clinical utility of 18F–choline PET/CT for primary metastasis staging of high-risk prostate cancer

Abstract Background The clinical utility of 18F–choline positron emission tomography fused with computed tomography (PET/CT) in all men with high-risk prostate cancer is still uncertain, because of selection of patients in previous studies. Prohibitive costs are one reason for PET/CT not being recommended for primary metastasis staging in European or American guidelines. The purpose of this retrospective study was to assess the clinical utility of in for primary metastasis staging in as complete a population as possible of men with high-risk prostate cancer. A secondary purpose was to evaluate whether a subgroup of these men could omit metastasis staging. Results In total 410 men were identified with high-risk prostate cancer. After exclusions, 317 men were initially considered for curative treatment; 213 (67%) had a choline PET/CT, with 43 men (20%) having positive findings. The risk of lymph node metastasis according to the Briganti nomogram showed a good discrimination between men with low and high risk of positive scans. Among the 35% of men with <20% risk according to the nomogram, only 1% had a positive scan, compared to 30% positive scans among the men who had higher risk. Conclusion 18F–choline PET/CT detects suspected metastases in one fifth of men with high-risk prostate cancer and should be considered for routine use. For men with <20% risk of metastasis according to the Briganti nomogram, imaging for metastasis staging might be omitted

Pre-treatment 18F-choline PET/CT is prognostic for biochemical recurrence, development of bone metastasis, and cancer specific mortality following radical local therapy of high-risk prostate cancer

Abstract Background The aim of this study was to determine whether lymph node metastasis on pre-treatment 18F-choline PET/CT is an independent prognostic factor for biochemical recurrence (BCR), skeletal metastasis, and cancer specific mortality (CSM), after radical local treatment (radical prostatectomy and/or radiotherapy) in men with high-risk prostate cancer. Medical records were reviewed for men with newly diagnosed high-risk prostate cancer who had pre-treatment 18F-choline positron emission tomography fused with computed tomography (PET/CT) scan for primary metastasis staging. Results Of 174 eligible men, 124 met the criteria for inclusion. The PET/CT scan was negative for metastasis in 97 (78%) men, inconclusive in 15 (12%), and positive in 12 (10%). The men with a positive PET/CT scan had significantly shorter time to BCR (p = 0.02), time to skeletal metastasis (p = 0.002), and time to prostate cancer specific death (p < 0.001). On multivariable Cox regression analysis, including also tumour stage, Gleason score, and PSA, a non-negative PET/CT scan was the only significant covariate for time to BCR (HR 2.6, 95% CI 1.3–5.5) and time to skeletal metastasis (HR 2.7, 95% CI 1.3–5.9). Conclusions In men with a newly diagnosed high-risk prostate cancer and a negative or inconclusive bone scan, 18F-choline uptake on PET/CT suggestive metastasis was associated with recurrence, progression to distant metastasis, and prostate cancer death. This strongly indicates that the choline uptakes represented metastasis and not false positive findings

Computed tomography urography with corticomedullary phase can exclude urinary bladder cancer with high accuracy

Background To evaluate the diagnostic accuracy of computed tomography-urography (CTU) to rule out urinary bladder cancer (UBC) and whether patients thereby could omit cystoscopy. Methods All patients evaluated for macroscopic hematuria with CTU with cortico-medullary phase (CMP) and cystoscopy at our institute between 1(st) November 2016 and 31(st) December 2019 were included. From this study cohort a study group consisting of all UBC patients and a control group of 113 patients randomly selected from all patients in the study cohort without UBC. Two radiologists blinded to all clinical data reviewed the CTUs independently. CTUs were categorized as positive, negative or indeterminate. Diagnostic accuracy and proportion of potential omittable cystoscopies were calculated for the study cohort by generalizing the results from the study group. Results The study cohort consisted of 2195 patients, 297 of which were in the study group (UBC group, n = 207 and control group, n = 90). Inter-rater reliability was high (kappa 0.84). Evaluation of CTUs showed that 174 patients were assesessed as positive (showing UBC), 46 patients as indeterminate (not showing UBC but with limited quality of CTU), and 77 patients as negative (not showing UBC with good quality of CTU). False negative rate was 0.07 (95%, CI 0.04-0.12), false positive rate was 0.01 (95% CI 0.0-0.07) and negative predictive value was 0.99 (95% CI 0.92-1.0). The area under the curve was 0.93 (95% CI 0.90-0.96). Only 2.9% (3/102) with high-risk tumors and 11% (12/105) with low- or intermediate-risk tumors had a false negative CTU. Cystoscopy could potentially have been omitted in 57% (1260/2195) of all evaluations. Conclusions CTU with CMP can exclude UBC with high accuracy. In case of negative CTU, it might be reasonable to omit cystoscopy, but future confirmative studies with possibly refined technique are needed.Funding Agencies|University of Gothenburg; Swedish government [ALFGBG-873181]; Department of Research and Development, NU-Hospital GroupNU Hospital Group</p

Simplified intraoperative sentinel-node detection performed by the urologist accurately determines lymph-node stage in prostate cancer.

Abstract Objective. The reference standard for lymph-node staging in prostate cancer is currently an extended pelvic lymph-node dissection (ePLND), which detects most, but not all, regional lymph-node metastases. As an alternative to ePLND, sentinel-node dissection with preoperative isotope injection and imaging has been reported. The objective was to determine whether intraoperative sentinel-node detection with a simplified protocol can accurately determine lymph-node stage in prostate cancer patients. Materials and methods. Patients with biopsy-verified high-risk prostate cancer with tumour stage T2-3 were included in the study. All patients underwent both ePLND and sentinel-node detection. (99m)Tc-marked nanocolloid was injected peritumourally by the operating urologist after induction of anaesthesia just before surgery. Sentinel nodes were detected both in vivo and ex vivo intraoperatively using a gamma probe. Sentinel nodes and metastases and their locations were recorded. Sensitivity and specificity were calculated. Results. At least one sentinel node was detected in 72 (87%) of the 83 patients. In 13 (18%) of these 72 patients sentinel nodes were detected outside the ePLND template. In six of these 13 patients, the Sentinel nodes from outside the template contained metastases, which proved to be the only metastases in two. For 12 patients the only metastatic deposit found was a micrometastasis (≤2 mm) in a sentinel node. In the 72 patients with detectable sentinel nodes, pathological analysis of the sentinel node correctly categorized 71 and ePLND 70 patients. Conclusions. This protocol yielded results comparable to the commonly used technique of sentinel-node detection, but with more cases of non-detection

(18)F-choline PET/CT for early detection of metastases in biochemical recurrence following radical prostatectomy.

Salvage radiotherapy (SRT) for biochemical recurrence (BCR) following radical prostatectomy (RP) should if possible be added at a prostate-specific antigen (PSA) level of <1-2 ng/mL. The value of positron emission tomography combined with computed tomography (PET/CT) at such low PSA values is not defined. The purpose was to determine what proportion of a well-defined cohort of hormone-naïve patients who were candidates for early salvage radiotherapy had (18)F-choline PET/CT findings suggesting metastases

Clinical Value of a Routine Urine Culture Prior to Transrectal Prostate Biopsy

Background: Infectious complications after a transrectal prostate biopsy may be severe. In Sweden, a routine culture prior to all prostate biopsies was introduced to enable targeted antimicrobial prophylaxis and reduce postbiopsy infections. Objective: To investigate whether a clinical routine with a urine culture prior to a prostate biopsy and targeted prophylactic antibiotic therapy reduces postbiopsy infections. Design, setting, and participants: In 2015, a site-specific antimicrobial stewardship programme with a urine culture prior to a prostate biopsy was initiated in Region Kronoberg. To evaluate this routine, we designed a population-based register study including all men who had an outpatient prostate biopsy in 2015–2019 and a control period including all men who had a biopsy in 2010–2014, when a urinary culture was obtained only on clinical suspicion. Outcome measurements and statistical analysis: The primary outcome was infectious complications within 10 d and the secondary outcome was a change in antibiotic prophylactic treatment. An infectious complication was defined as prescription of antibiotics for urinary tract infections or admission to hospital for urinary tract infections or sepsis after a biopsy. Results and limitations: The urine culture period included 2971 prostate biopsy procedures, of which 2684 (90%) were preceded by a urine culture. The control period included 2818 procedures, of which 135 (4.8%) were preceded by a urine culture. Infectious complications were slightly more common during the urine culture period (5.0%) than during the control period (4.3%, p = 0.17), as was inpatient care for infections (3.5% vs 2.2%, p = 0.002). The routine identified 5.4% men with asymptomatic bacteriuria. Despite targeted antibiotic treatment (1.5% received a nonfluoroquinolone treatment), the rate of infectious complications (6.3%) was similar to that in the control period. Conclusions: Prebiopsy urine culture did not lead to fewer postbiopsy infections. Other measures are needed to reduce infectious complications after a prostate biopsy. Patient summary: In this report, we evaluated a routine with urine culture prior to a transrectal prostate biopsy and found that it did not lead to fewer infectious complications