External validation of nomograms including MRI features for the prediction of side-specific extraprostatic extension.

BACKGROUND: Prediction of side-specific extraprostatic extension (EPE) is crucial in selecting patients for nerve-sparing radical prostatectomy (RP). Multiple nomograms, which include magnetic resonance imaging (MRI) information, are available predict side-specific EPE. It is crucial that the accuracy of these nomograms is assessed with external validation to ensure they can be used in clinical practice to support medical decision-making. METHODS: Data of prostate cancer (PCa) patients that underwent robot-assisted RP (RARP) from 2017 to 2021 at four European tertiary referral centers were collected retrospectively. Four previously developed nomograms for the prediction of side-specific EPE were identified and externally validated. Discrimination (area under the curve [AUC]), calibration and net benefit of four nomograms were assessed. To assess the strongest predictor among the MRI features included in all nomograms, we evaluated their association with side-specific EPE using multivariate regression analysis and Akaike Information Criterion (AIC). RESULTS: This study involved 773 patients with a total of 1546 prostate lobes. EPE was found in 338 (22%) lobes. The AUCs of the models predicting EPE ranged from 72.2% (95% CI 69.1-72.3%) (Wibmer) to 75.5% (95% CI 72.5-78.5%) (Nyarangi-Dix). The nomogram with the highest AUC varied across the cohorts. The Soeterik, Nyarangi-Dix, and Martini nomograms demonstrated fair to good calibration for clinically most relevant thresholds between 5 and 30%. In contrast, the Wibmer nomogram showed substantial overestimation of EPE risk for thresholds above 25%. The Nyarangi-Dix nomogram demonstrated a higher net benefit for risk thresholds between 20 and 30% when compared to the other three nomograms. Of all MRI features, the European Society of Urogenital Radiology score and tumor capsule contact length showed the highest AUCs and lowest AIC. CONCLUSION: The Nyarangi-Dix, Martini and Soeterik nomograms resulted in accurate EPE prediction and are therefore suitable to support medical decision-making.

Is cribriform pattern in prostate biopsy a risk factor for metastatic disease on 68Ga-PSMA-11 PET/CT?

INTRODUCTION: Cribriform growth pattern (CP) in prostate cancer (PCa) has been associated with different unfavourable oncological outcomes. This study addresses if CP in prostate biopsies is an independent risk factor for metastatic disease on PSMA PET/CT. METHODS: Treatment-naive patients with ISUP GG ≥ 2 staged with 68Ga-PSMA-11 PET/CT diagnosed from 2020 to 2021 were retrospectively enrolled. To test if CP in biopsies was an independent risk factor for metastatic disease on 68Ga-PSMA PET/CT, regression analyses were performed. Secondary analyses were performed in different subgroups. RESULTS: A total of 401 patients were included. CP was reported in 252 (63%) patients. CP in biopsies was not an independent risk factor for metastatic disease on the 68Ga-PSMA PET/CT (p = 0.14). ISUP grade group (GG) 4 (p = 0.006), GG 5 (p = 0.003), higher PSA level groups per 10 ng/ml until > 50 (p-value between 0.02 and > 0.001) and clinical EPE (p > 0.001) were all independent risk factors. In the subgroups with GG 2 (n = 99), GG 3 (n = 110), intermediate-risk group (n = 129) or the high-risk group (n = 272), CP in biopsies was also not an independent risk factor for metastatic disease on 68Ga-PSMA PET/CT. If the EAU guideline recommendation for performing metastatic screening was applied as threshold for PSMA PET/CT imaging, in 9(2%) patients, metastatic disease was missed, and 18% fewer PSMA PET/CT would have been performed. CONCLUSION: This retrospective study found that CP in biopsies was not an independent risk factor for metastatic disease on 68Ga-PSMA PET/CT.

Circulating tumour cells to drive the use of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer.

BACKGROUND: Guidelines recommend neoadjuvant chemotherapy (NAC) for the treatment of nonmetastatic muscle-invasive bladder cancer (MIBC). NAC is, however, underutilized in practice because of its associated limited overall survival (OS) benefit and significant treatment-related toxicity. We hypothesized that the absence of circulating tumour cells (CTCs) identifies MIBC patients with such a favourable prognosis that NAC may be withheld. PATIENTS AND METHODS: The CirGuidance study was an open-label, multicentre trial that included patients with clinical stage T2-T4aN0-N1M0 MIBC, scheduled for radical cystectomy. CTC-negative patients (no CTCs detectable using the CELLSEARCH system) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC, followed by radical surgery. The primary endpoint was the 2-year OS in the CTC-negative group with a prespecified criterion for trial success of ≥75% (95% confidence interval (CI) ±5%). RESULTS: A total of 273 patients were enrolled. Median age was 69 years; median follow-up was 36 months. The primary endpoint of 2-year OS in the CTC-negative group was 69.5% (N = 203; 95% CI 62.6%-75.5%). Two-year OS was 58.2% in the CTC-positive group (N = 70; 95% CI 45.5%-68.9%). CTC-positive patients had a higher rate of cancer-related mortality [hazard ratio (HR) 1.61, 95% CI 1.05-2.45, P = 0.03] and disease relapse (HR 1.87, 95% CI 1.28-2.73, P = 0.001) than CTC-negative patients. Explorative analyses suggested that CTC-positive patients who had received NAC (n = 22) survived longer than CTC-positive patients who had not (n = 48). CONCLUSION: The absence of CTCs in MIBC patients was associated with improved cancer-related mortality and a lower risk of disease relapse after cystectomy; however, their absence alone does not justify to withhold NAC. Exploratory analyses suggested that CTC-positive MIBC patients might derive more benefit from NAC. TRIAL REGISTRATION: Netherlands Trial Register NL3954; https://www.trialregister.nl/trial/3954.

Interrater agreement of contouring of the neurovascular bundles and internal pudendal arteries in neurovascular-sparing magnetic resonance-guided radiotherapy for localized prostate cancer.

BACKGROUND AND PURPOSE: Radiation damage to neural and vascular tissue, such as the neurovascular bundles (NVBs) and internal pudendal arteries (IPAs), during radiotherapy for prostate cancer (PCa) may cause erectile dysfunction. Neurovascular-sparing magnetic resonance-guided adaptive radiotherapy (MRgRT) aims to preserve erectile function after treatment. However, the NVBs and IPAs are not routinely contoured in current radiotherapy practice. Before neurovascular-sparing MRgRT for PCa can be implemented, the interrater agreement of the contouring of the NVBs and IPAs on pre-treatment MRI needs to be assessed. MATERIALS AND METHODS: Four radiation oncologists independently contoured the prostate, NVB, and IPA in an unselected consecutive series of 15 PCa patients, on pre-treatment MRI. Dice similarity coefficients (DSCs) for pairwise interrater agreement of contours were calculated. Additionally, the DCS of a subset of the inferior half of the NVB contours (i.e. approximately prostate midgland to apex level) was calculated. RESULTS: Median overall interrater DSC for the left and right NVB was 0.60 (IQR: 0.54 - 0.68) and 0.61 (IQR: 0.53 - 0.69) respectively and for the left and right IPA 0.59 (IQR: 0.53 - 0.64) and 0.59 (IQR: 0.52 - 0.64) respectively. Median overall interrater DSC for the inferior half of the left NVB was 0.67 (IQR: 0.58 - 0.74) and 0.67 (IQR: 0.61 - 0.71) for the right NVB. CONCLUSION: We found that the interrater agreement for the contouring of the NVB and IPA improved with enhancement of the MRI sequence as well as further training of the raters. The agreement was best in the subset of the inferior half of the NVB, where a good agreement is clinically most relevant for neurovascular-sparing MRgRT for PCa.

Nerve Sparing during Robot-Assisted Radical Prostatectomy Increases the Risk of Ipsilateral Positive Surgical Margins.

PURPOSE: Available published studies evaluating the association between nerve sparing robot-assisted radical prostatectomy and risk of ipsilateral positive surgical margins were subject to selection bias. In this study we overcome these limitations by using multivariable regression analysis. MATERIALS AND METHODS: Patients undergoing robot-assisted radical prostatectomy for prostate cancer at 4 institutions from 2013 to 2018 were included in the study. A multilevel logistic random intercept model, including covariates on patient level and side specific factors on prostate lobe level, was used to evaluate the association between nerve sparing and risk of ipsilateral positive margins. RESULTS: A total of 5,148 prostate lobes derived from 2,574 patients who underwent robot-assisted radical prostatectomy were analyzed. Multivariable analysis showed nerve sparing was an independent predictor for ipsilateral positive margins (OR 1.42, 95% CI 1.14-1.82). Other significant predictors for positive margins were prostate specific antigen density (OR 3.64, 95% CI 2.36-5.90) and side specific covariates including highest preoperative ISUP (International Society of Urological Pathology) biopsy grade (OR 1.58, 95% CI 1.13-2.53; OR 1.62, 95% CI 1.13-2.69; OR 2.11, 95% CI 1.39-3.59 and OR 4.43, 95% CI 3.17-10.12 for ISUP grade 2, 3, 4 and 5, respectively), presence of extraprostatic extension on magnetic resonance imaging (OR 1.42, 95% CI 1.03-1.91) and percentage of positive cores on systematic biopsy (OR 3.82, 95% CI 2.50-5.86). CONCLUSIONS: Nerve sparing was associated with an increased risk of ipsilateral positive surgical margins. The increased risk of positive margins should be considered when counseling patients who opt for nerve sparing robot-assisted radical prostatectomy.

Reduce bladder cancer recurrence in patients treated for upper urinary tract urothelial carcinoma: The REBACARE-trial.

BACKGROUND: Following radical nephro-ureterectomy for urothelial carcinoma of the upper urinary tract (UUT), the reported bladder recurrence rate of urothelial carcinoma is 22-47%. A single intravesical instillation of chemotherapy within 10 days following nephro-ureterectomy has the potential to decrease the risk of a bladder recurrence significantly. Despite recommendation by the European Association of Urology guideline to administer a single instillation postoperatively, the compliance rate is low because the risk of extravasation of chemotherapy. AIM: To reduce the risk of bladder cancer recurrence by a single intravesical instillation of Mitomycin immediately (within 3 h) before radical nephro-ureterectomy or partial ureterectomy. METHODS: Adult patients (age ≥ 18 years) with a (suspicion of a) urothelial carcinoma of the UUT undergoing radical nephro-ureterectomy or partial ureterectomy will be eligible and will receive a single intravesical instillation of Mitomycin within 3 h before surgery. In total, 170 patients will be included in this prospective, observational study. Follow-up will be according to current guidelines. RESULTS: The primary endpoint is the bladder cancer recurrence rate up to two years after surgery. Secondary endpoints are: a) the compliance rate; b) oncological outcome; c) possible side-effects; d) the quality of life; e) the calculation of costs of a single neoadjuvant instillation with Mitomycin and f) molecular characterization of UUT tumors and intravesical recurrences. CONCLUSIONS: A single intravesical instillation of Mitomycin before radical nephro-ureterectomy or partial ureterectomy may reduce the risk of a bladder recurrence in patients treated for UUT urothelial carcinoma and will circumvent the disadvantages of current therapy.

Diffuse bone metastases on (68)Ga-PSMA PET-CT in a patient with prostate cancer and normal bone scan.

A 75-year-old patient was diagnosed with a Gleason 9 prostate carcinoma. His PSA level was 50.4 ng/ml. Routine bone scintigraphy was negative for metastasis (a). Due to the high tumour grading and relatively high PSA level, (68)Ga-PSMA PET-CT was ordered to rule out distant metastases. This scan showed numerous skeletal lesions with high tracer accumulation as sign of diffuse osseous metastases (b). On low-dose CT there were no signs of sclerosis (c). (68)Ga-PSMA PET-CT also showed high uptake in the prostate and in para-iliac and para-aortal lymph nodes, without lymph node enlargement. No bone biopsy was obtained to confirm the metastases. Due to this result, the treatment plan was changed to systemic therapy, instead of local therapy.

One 24-hour frequency-volume chart in a woman with objective urinary motor urge incontinence is sufficient.

OBJECTIVES: To determine whether one 24-hour frequency-volume (FV) chart in a woman with objective urinary motor urge incontinence is sufficient to gain insight into her voiding habits. METHODS: Retrospectively, women 18 years old and older with urodynamically confirmed urinary motor urge incontinence without neurologic disease or other urologic pathologic findings, who correctly completed two or three 24-hour FV charts during normal daily life, were studied. For each patient, we compared the voiding parameters (mean voided volume, diuria, nocturia, minimum and maximum voided volumes, and total voided volume) and fluid intake calculated from the first FV chart with the same data calculated from all the FV charts. RESULTS: Ninety-eight adult women were recruited. A marked dropout occurred, and 60 patients remained to be evaluated (mean age 54.5 +/- 15.5 years). The calculated voiding parameters agreed with those in published reports. Strong associations existed between all voiding parameters and fluid intake calculated from the first FV chart and those calculated from all FV charts (P <0.001 for all parameters). Compared with the well-known variability, the differences between the voiding parameters calculated from the first FV chart and those from all charts were small. These results agreed with studies in other patient groups (benign prostatic hyperplasia and interstitial cystitis) that analyzed the use of only one 24-hour FV chart. CONCLUSIONS: The use of only one 24-hour FV chart completed during normal daily life by a woman with objective urinary motor urge incontinence is sufficient to gain insight into her voiding habits.

Prevalence and bothersomeness of lower urinary tract symptoms in benign prostatic hyperplasia and their impact on well-being.

PURPOSE: We established the prevalence and bothersomeness of symptoms and their impact on well-being in a large group of strictly selected men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Included in our study were 475 consecutive men who met the criteria of the International Consensus Committee on BPH and voided more than 150 ml. during uroflowmetry. International Prostate Symptom Scores and quality of life score were determined. We included the 7 bothersomeness questions of the Symptom Problem Index and the 4 of the BPH Impact Index of the American Urological Association Measurement Committee. These questions refer to the degree of bothersomeness caused by urinary problems and how they affect various health domains. RESULTS: The symptoms with the highest prevalence based on mean scores were weak urinary stream, frequency and urgency. Urgency, nocturia and hesitancy were the most bothersome symptoms. Patients were only discouraged from performing normal daily activity when the symptom index exceeded 20. Incomplete emptying and frequency bothersomeness correlated strongly, and weak urinary stream and hesitancy bothersomeness correlated weakly with all health and quality of life domains. CONCLUSIONS: Weak urinary stream, frequency and urgency were the most prevalent symptoms, while urgency, nocturia and hesitancy were the most bothersome symptoms. In contrast to weak urinary stream and hesitancy, the bothersomeness of incomplete emptying and frequency was strongly associated with well-being.

Room oxygen enrichment improves sleep and subsequent day-time performance at high altitude.

We carried out a randomized, double-blind trial at 3800 m altitude to test whether a small degree of room oxygen enrichment at night improves sleep quality, and performance and well-being the following day. Eighteen sea-level residents drove from sea level to 3800 m in one day, and then slept one night in ambient air, and another night in 24% oxygen, the order being randomized. With oxygen enrichment the subjects had fewer apneas (P < 0.01) and spent less time in periodic breathing with apneas (P < 0.01) than when they slept in ambient air. Subjective assessments of sleep quality were also significantly improved. There was a lower acute mountain sickness score during the morning after oxygen-enriched sleep (P < 0.01) and a greater increase in arterial oxygen saturation from evening to morning (P < 0.05). The larger increases in arterial oxygen saturation from evening to morning suggest that the control of breathing may have been altered. Installing an oxygen-enriched room at high altitude is relatively simple and inexpensive, and shows promise for improving well-being of both commuters and residents.