Validation of the 21-Gene Recurrence Score Assay in Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer and 0 to 3 Positive Lymph Nodes: Risk Pattern and Outcomes on a Community Level.

Introduction: The aim of the present study was to analyze the performance of Oncotype DX® multigene assay (ODX®) in patients with 0-3 lymph nodes in a high-volume community hospital. Methods: Patients with non-metastatic HR*/HER2- EBC and 0-3 positive lymph nodes, who underwent primary surgery at the Red Cross Hospital Munich, Germany and consecutively had ODX® testing were included in this retrospective study. The distribution of clinicopathologic characteristics, recurrence score (RS) risk, and use of systemic therapy were compared among patients without positive lymph nodes (N0) and patients with micrometastases or 1 to 3 positive lymph nodes (N1). Disease-free survival (DFS) and overall survival (OS) were estimated. Results: From 2012 to 2017 ODX® was consecutively performed in 575 (16.4%) of 3,492 women with HR*/HER- EBC, of which 553 were eligible for this analysis (N0: 60.8%; N1: 39.2%). Among the patients included, 441 (79.7%) had an RS of 0 to 25 and 112 (20.3%) had an RS of 26 or higher. In patients with RS 0 to 25 the rate of chemotherapy use was low, independent from nodal status (N0: 17.1% and N1: 19.1%) and 5-year DFS was 90.5% and 91.7% for N0 and N1 patients, respectively. There was no significant difference in DFS (90.5% vs. 93.3%; p = 0.101) or OS (97.2% vs. 96.0%; p = 0.737) for patients with an RS of 0 to 25 when treated with chemo-endocrine therapy or endocrine therapy alone, independent from nodal status. Conclusions: The results of the study confirm the observations from randomized studies on the use of the ODX® in a real-world population in terms of risk distribution and patient outcome. Adjuvant chemotherapy could be safely omitted in patients with HR*/HER2- breast cancer with 0-3 positive lymph nodes and RS <25.

PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients.

BACKGROUND: PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. MATERIAL AND METHODS: The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. RESULTS: The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; p = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR >2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; p = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; p = 0.014). CONCLUSION: In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

Post-Neoadjuvant Gemcitabine and Cisplatin with Regional Hyperthermia for Patients with Triple-Negative Breast Cancer and Non-pCR after Neoadjuvant Chemotherapy: A Single-Institute Experience.

BACKGROUND: Patients with triple-negative primary breast cancer (TNBC) who have residual invasive carcinoma after neoadjuvant chemotherapy have poor prognosis. Proven adjuvant approaches to reduce the risk of recurrence and improve outcome in patients with non-pathological complete response (non-pCR) are limited. METHODS: From our institutional registry, a consecutive case series of patients with operable, unilateral, primary invasive noninflammatory early TNBC of stage I-IIIB and pathologically verified residual cancer cells (no pathological complete response) after neoadjuvant chemotherapy underwent adjuvant treatment with gemcitabine plus cisplatin combined with regional hyperthermia. For quality assurance, we analyzed feasibility, efficacy, and toxicity of all treated patients. Outcome was evaluated for the entire group of patients as well as for the subgroups of patients with or without lymph node involvement at baseline (cN0/ cN+). RESULTS: From August 2012 to January 2019, we offered this treatment to 53 patients at our center as part of routine care. The median follow-up was 38 months. The majority of patients (64.2%) had cT2 tumors at baseline. Twenty-four patients (45%) were clinically node positive as evaluated by sonography. Thirty-nine patients (74%) had grade 3, and 14 patients (26%) had grade 2 tumors. Forty-one patients (76%) showed a regression grade 1 according to Sinn. Patients received a median of six treatment cycles of gemcitabine and cisplatin (range 1-6) combined with 12 applications of regional hyperthermia (median 12, range 2-12). Disease-free survival (DFS) at 3 years was 57.5%. In patients with no lymph node involvement at baseline (cN0), DFS at 3 years was significantly higher than in initially node-positive (cN+) patients (80 vs. 31%; p = 0.001). Overall survival (OS) at 3 years was 81.6%. In patients with no lymph node involvement at baseline (cN0), OS at 3 years was significantly higher than in node-positive (cN+) patients (93 vs. 70.4%; p = 0.02). Overall, grade 3/4 toxicities were leukopenia (38%), thrombocytopenia (4%), and anemia (4%). CONCLUSION: After standard neoadjuvant chemotherapy containing anthracycline plus cyclophosphamide followed by taxanes, addition of adjuvant gemcitabine plus cisplatin in combination with regional hyperthermia was safe and effective in TNBC patients with non-pCR.

PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer.

BACKGROUND: Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients' risk of recurrence based on molecular tumor characteristics. PRIMARY OBJECTIVES: To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy STUDY HYPOTHESIS: Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs. TRIAL DESIGN: A multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm). MAJOR INCLUSION/EXCLUSION CRITERIA: Women aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1). ENDPOINTS: The primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs. SAMPLE SIZE: 500 eligible and evaluable patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Estimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).

Detection of early breast cancer beyond mammographic screening: a promising biomarker panel.

Aim: We assessed the suitability of a biomarker panel to improve early detection and individual risk assessment in breast cancer (BC) patients. Materials & methods: PENK, pro-SP, hGH and CA15-3 of 204 BC patients and 68 healthy controls were measured. Results: PENK and human growth hormone concentrations were significantly lower and pro-SP values higher in BC patients compared with controls. C-index increased from 0.628 for CA15-3 alone to 0.754 when all three biomarkers were added to the model. Conclusion: This biomarker panel may improve early detection of BC and influence the assessment of breast imaging. It might be useful for a risk-adapted cancer surveillance or primary prevention program by a more precise determination of an individualized BC risk.

Spatio-temporal deep learning models for tip force estimation during needle insertion.

PURPOSE: Precise placement of needles is a challenge in a number of clinical applications such as brachytherapy or biopsy. Forces acting at the needle cause tissue deformation and needle deflection which in turn may lead to misplacement or injury. Hence, a number of approaches to estimate the forces at the needle have been proposed. Yet, integrating sensors into the needle tip is challenging and a careful calibration is required to obtain good force estimates. METHODS: We describe a fiber-optic needle tip force sensor design using a single OCT fiber for measurement. The fiber images the deformation of an epoxy layer placed below the needle tip which results in a stream of 1D depth profiles. We study different deep learning approaches to facilitate calibration between this spatio-temporal image data and the related forces. In particular, we propose a novel convGRU-CNN architecture for simultaneous spatial and temporal data processing. RESULTS: The needle can be adapted to different operating ranges by changing the stiffness of the epoxy layer. Likewise, calibration can be adapted by training the deep learning models. Our novel convGRU-CNN architecture results in the lowest mean absolute error of [Formula: see text] and a cross-correlation coefficient of 0.9997 and clearly outperforms the other methods. Ex vivo experiments in human prostate tissue demonstrate the needle's application. CONCLUSIONS: Our OCT-based fiber-optic sensor presents a viable alternative for needle tip force estimation. The results indicate that the rich spatio-temporal information included in the stream of images showing the deformation throughout the epoxy layer can be effectively used by deep learning models. Particularly, we demonstrate that the convGRU-CNN architecture performs favorably, making it a promising approach for other spatio-temporal learning problems.

Quality of life in breast cancer patients and surgical results of immediate tissue expander/implant-based breast reconstruction after mastectomy.

OBJECTIVES: The purpose of this study was to analyze the effects of prior radiotherapy (RT) as well as postmastectomy radiotherapy (PMRT) on patient-reported quality of life (QoL) and on surgical/aesthetic outcomes in patients with expander-/implant-based delayed immediate reconstruction (EIBR) compared to patients that underwent EIBR without any RT. MATERIAL AND METHODS: QoL was assessed by BREAST-Q, the surgical/aesthetic outcome by a structured examination and a picture analysis (BCCT.CORE software) and subsequently compared between the three cohorts. RESULTS: Of 161 eligible patients, 97 followed the invitation (no RT n = 54, 9 of them with bilateral EIBR; PMRT n = 26; history of RT n = 15). The surgical/aesthetic results were better in the RT-naive cohort than in the PMRT cohort, but satisfaction with outcome and psychosocial well-being were better in the PMRT cohort. The RT-naive cohort showed (significantly) higher scores in satisfaction with breast, satisfaction with implant and sexual well-being compared to the history of RT cohort, although satisfaction with outcome was comparable. The PMRT cohort reached significantly more points in almost all categories and better BCCT.CORE and examination results than the history of RT cohort. Of all patients, 92.7%, 84.6% and 78.6% (RT naive, PMRT, history of RT) would agree to undergo EIBR again. CONCLUSION: EIBR results in acceptable QoL and surgical results. In patients with a prior RT, QoL is significantly lower and surgical results are significantly worse. However, high acceptance rates suggest EIBR being a justifiable option even for this group. Prospective studies and long-term follow-up are required for definitive conclusions.

Influence of Different Methods of Intrapartum Analgesia on the Progress of Labour and on Perinatal Outcome.

Background Various methods of intrapartum analgesia are available these days. Pethidine, meptazinol and epidural analgesia are among the most commonly used techniques. A relatively new one is patient-controlled intravenous analgesia with remifentanil, although the experiences published so far in Germany are limited. Our goal was to study the influence of these analgesic techniques (opioids vs. patient-controlled intravenous analgesia with remifentanil vs. epidural analgesia) on the second stage of labour and on perinatal outcome. Material and Methods We conducted a retrospective study with 254 parturients. The women were divided into 4 groups based on the analgesic technique and matched for parity, maternal age and gestational age (opioids n = 64, patient-controlled intravenous analgesia with remifentanil n = 60, epidural analgesia n = 64, controls without the medicinal products mentioned n = 66). Maternal, fetal and neonatal data were analysed. Results The expulsive stage was prolonged among both primiparas and multiparas with patient-controlled intravenous analgesia with remifentanil (79 [74] vs. 44 [55] min, p = 0.016, and 28 [68] vs. 10 [11] min, p < 0.001, respectively) and epidural analgesia (90 [92] vs. 44 [55] min, p = 0.004, and 22.5 [73] vs. 10 [11] min, p = 0.003, respectively) compared with the controls. The length of the pushing stage was similar among primiparas in all groups but prolonged compared with the controls in multiparas with patient-controlled intravenous analgesia with remifentanil (15 [17] vs. 5 [7] min, p = 0.001) and epidural analgesia (10 [15] vs. 5 [7] min, p = 0.006). The Apgar, umbilical arterial pH and base excess values were similar between the groups, as were the rates of acidosis and neonatal intensive care unit admission. Conclusion Parturients with patient-controlled intravenous analgesia with remifentanil and epidural analgesia showed a prolonged expulsive stage compared with the opioid group and controls. The short-term neonatal outcome was not influenced by the three methods examined.

Urinary symptoms, quality of life, and patient satisfaction in genetic and sporadic hereditary spastic paraplegia.

BACKGROUND: Urinary involvement is common in hereditary spastic paraplegias (HSPs), but has rarely been assessed systematically. METHODS: We characterized urinary complaints in 71 German HSP patients (mean age 55.4 ± 13.9 years; mean disease duration 20.7 ± 14.3 years; 48% SPG4-positive) using validated clinical rating scales (SCOPA-AUT, ICIQ-SF, ICIQ-LUTSqol). Treatment history and satisfaction with medical care was also assessed. RESULTS: 74.6% of patients had one or more urological problems, most commonly nocturia and urgency. Incontinence was more severe in women, correlating with SCOPA-AUT. Female gender and SPG4 mutations were associated with higher urinary frequency and severity of urological involvement. QoL was overall reduced, more in women and in SPG4 mutation carriers. Almost 90% consulted a medical specialist; more than half were largely satisfied. 43.4% received oral medication and 5.7% received intravesical botulinum toxin. However, more than one-third of patients remained untreated. CONCLUSION: Urinary complaints are common in HSP and should be addressed and treated.

Endometrial cancer-how many patients could benefit from sentinel lymph node dissection?

BACKGROUND: Sentinel lymph node dissection (SLND) may reduce morbidity in patients with endometrial cancer. The objective of this study is to estimate how many systematic lymph node dissections (LND) can be spared with an implementation of a SLN-procedure. METHODS: Retrospective, single-center study, SLND according to NCCN-Guidelines. RESULTS: In 109 patients of 154 consecutive patients, SLND was performed. The detection rate was 61% on both sides and 86% on at least one side. Classification of uterine risk factors is as follows: low risk 53, intermediate risk 25, high-intermediate risk 13, and high-risk 18. Stage IIIC: 0, 3, 7, 11, respectively. Under the assumption that 56 patients with "higher than low risk" factors would be treated by systematic LND, we spared 26 pelvic and paraaortic LND. After failures of SLN detection, unilateral pelvic LND was performed in 15 patients. Patients with "higher than low risk" factors and node-negative SLN are candidates for a randomized study to prove safety and efficacy. Only every third patient in our study met these criteria. CONCLUSIONS: In a cohort of patients with "higher than low risk" endometrial cancer, the implementation of SLND nearly divided the number of radical lymph node dissections in half. Further studies are required to define the best modalities for SLND.

Evaluation of the diagnostic value of preoperative sentinel lymph node (SLN) imaging in penile carcinoma patients without palpable inguinal lymph nodes via single photon emission computed tomography/computed tomography (SPECT/CT) as compared to planar scintigraphy.

BACKGROUND: Sentinel lymph node (SLN) biopsy represents a well-established diagnostic tool for the assessment of lymphatic metastasis. Correct pre- and intraoperative visualization of SLN is of the utmost importance to ensure the safety and feasibility of the procedure. Aim of this study was to evaluate the diagnostic value of preoperative SLN imaging via single photon emission computed tomography/computed tomography (SPECT/CT) and planar scintigraphy in patients with penile carcinoma with nonpalpable inguinal lymph nodes. MATERIALS AND METHODS: After peritumoral intradermal tracer injection (150MBq/4.05mCi Tc-99m nanocolloid), we acquired planar scintigraphies including indirect body contouring using a twin head gamma camera. Subsequently we acquired SPECT/CT images of the abdomen via a hybrid system. Prospective evaluation of 52 groins in 26 examined patients was done for all image files obtained with both techniques by 2 trained experts in consensual assessment. RESULTS: A total of 71 SLNs in 37 groins were identified by means of planar scintigraphy. In these images, no radiolabeled lymph nodes were visualized in 15 out of 52 groins (28.8%). The SPECT/CT images showed a total of 82 SLNs in 42 groins. In 19.2% (10 of the 52 groins), there was no visualization of lymph nodes in SPECT/CT. 8 SLNs in 7 groins that were visualized in the planar technique were found to be false positive by SPECT/CT. In total, 19 SLNs in 16 groins that were overlooked by planar imaging could only be detected by SPECT/CT. In contrast to planar scintigraphy, SPECT/CT imaging enabled clear and precise anatomical localization of SLNs in all 42 groins where radiolabeled SLNs were visible. Even under consideration of all lymphatic drainage regions, statistical evaluation showed a significantly higher number of detected SLNs with SPECT/CT in comparison to the planar technique (P = 0.0022). CONCLUSION: In these patients SPECT/CT is capable of visualizing SLNs that cannot be detected with planar imaging. The SPECT/CT technique reduces the number of false positive findings from planar SLN imaging and is able to show anatomic SLN localization more precisely. If possible, preoperative SLN imaging should be performed by means of the SPECT/CT technique in patients with this tumor entity.

Mode of Delivery and Pregnancy Outcome in Women with Congenital Heart Disease.

BACKGROUND: Advances in cardiac surgery and congenital cardiology have led to an increasing number of women with congenital heart disease (CHD) reaching childbearing age. In general, cardiologists recommend vaginal delivery for women with CHD to avoid complications from Caesarean section as many women with CHD tolerate vaginal delivery well. METHODS AND RESULTS: This is a single-center study comparing mode of delivery, pregnancy outcome, indications for Caesarean section and induction of labor between women with and without CHD. A historical cohort study was conducted including 116 patients with CHD. An individual threefold matching with 348 women without CHD was carried out. Caesarean section was performed in 46.6% of pregnancies with CHD (33.6% without CHD, P = 0.012). Primary Caesarean section increases with severity of CHD (P = 0.036), 33.3% of women with CHD had primary planned Caesarean section due to cardiac reasons. Induction of labor was performed in 45.7% of attempted vaginal deliveries in women with CHD (27.9% without CHD, P = 0.001). Lower mean birth weight (P = 0.004) and Small for Gestational Age (SGA) (P < 0.001) were more common in women with CHD. One CHD patient suffered from postpartum hemorrhage. CONCLUSIONS: Concerns about maternal deterioration resulting in higher rates of induction of labor seem unjustified in most cases. Along with a possible reduction of Caesarean section on maternal request, a reduction of planned vaginal delivery may be expedient in reducing the rate of Caesarean section in women with CHD.

Preserved micturition after intradetrusor onabotulinumtoxinA injection for treatment of neurogenic bladder dysfunction in Parkinson's disease.

BACKGROUND: To assess the efficacy and safety of intradetrusor onabotulinumtoxinA (OnabotA) injection treatment in patients with neurogenic lower urinary tract dysfunction (NLUTD), especially for patients with Parkinson disease (PD). METHODS: PD patients refractory to oral antimuscarinic participated in an off-label use study and were evaluated prior and after 200 IU OnabotA injection into detrusor muscle, including trigone. Changes due to treatment were evaluated using bladder diaries, urodynamics, and questionnaires. Statistical analysis comprised Wilcoxon rank-sum test. Values are presented as mean ± standard deviation. RESULTS: Ten PD patients (4 female and 6 male, mean age: 67.9 ± 5.36 years) with LUTD were enrolled. All patients tolerated the treatment. Bladder diary variables decreased significantly (p ≤ 0.011) after OnabotA injection compared to variables prior injection. Desire to void and maximum bladder capacity increased significantly in urodynamics (p ≤ 0.05). Maximum detrusor pressure during voiding phase normalised from 56.2 to 18.75 cm/H20. Detrusor overactivity was less often detectable. All patients voided spontaneously. Mean post void residual (PVR) volume was 77.0 ± 119.78 mL postoperatively. No urinary retention or side effects have been observed during/after treatment. Mean follow-up time was 4 months (range of 1-12). 4 patients requested repeated injection after a mean period of 10 months between first and second injection. CONCLUSIONS: Our data confirm the efficacy and safety of 200 IU OnabotA injection in patients with neurogenic LUTD due to PD. The risk of urinary retention or high post-urinary residual volumes seems to be minor after OnabotA-injection. More research is needed with larger sample size to confirm the significance of these findings. TRIAL NUMBER: ISRCTN 11857462 , Registration Date 2016/10/08.

Cancer-specific and overall survival in patients with recurrent prostate cancer who underwent salvage extended pelvic lymph node dissection.

BACKGROUND: The aim was to evaluate cancer-specific survival (CSS) and overall survival (OS) in patients with prostate cancer (PCa) recurrence who underwent salvage extended pelvic lymph node dissection (ePLND), taking into consideration pre- and postoperative androgen deprivation therapy (ADT). METHODS: Salvage ePLND was performed in a cohort of 54 patients with PCa recurrence, and data from 45 patients were analyzed. The indications for salvage ePLND were biochemical recurrence (BCR) of PCa and suspect findings on (11)C-choline PET/CT. PSA-level, biochemical response (BR), duration of biochemical recurrence freedom (BCRF), number of metastases, OS and CSS were analyzed retrospectively. RESULTS: The average follow-up was 42.7 ± 20.8 months. Thirty-three patients (73.3 %, 95 % CI: 60.5-83.6 %) achieved BCRF during follow-up. The mean BCRF-period was 31.4 ± 19.7 months. CSS and OS were both 91.7 % ± 4.8 % (3-year survival) and 80.6 ± 8.6 % (5-year survival). Twenty-four patients (53.3 %, 95 % CI: 40.0-66.3 %) with castration-resistant PCa (CRPC) responded again to ADT after salvage ePLND. CONCLUSIONS: Salvage ePLND for selected patients with BCR and clinically recurrent nodal disease can achieve an immediate complete PSA response (i. e. BCRF) in nearly half of the patients. Patients with CRPC responded again to ADT after ePLND. Multicenter prospective studies with a control group are needed.

A Multicenter Randomized Noninferiority Trial Comparing GreenLight-XPS Laser Vaporization of the Prostate and Transurethral Resection of the Prostate for the Treatment of Benign Prostatic Obstruction: Two-yr Outcomes of the GOLIATH Study.

BACKGROUND: The GOLIATH study is a 2-yr trial comparing transurethral resection of prostate (TURP) to photoselective vaporization with the GreenLight XPS Laser System (GL-XPS) for the treatment of benign prostatic obstruction (BPO). Noninferiority of GL-XPS to TURP was demonstrated based on a 6-mo follow-up from the study. OBJECTIVE: To determine whether treatment effects observed at 6 mo between GL-XPS and TURP was maintained at the 2-yr follow-up. DESIGN, SETTING, AND PARTICIPANTS: Prospective randomized controlled trial at 29 centers in nine European countries involving 281 patients with BPO. INTERVENTION: Photoselective vaporization using the 180-W GreenLight GL-XPS or conventional (monopolar or bipolar) TURP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the International Prostate Symptom Score for which a margin of three was used to evaluate the noninferiority of GL-XPS. Secondary outcomes included Qmax, prostate volume, prostate specific antigen, Overactive Bladder Questionnaire Short Form, International Consultation on Incontinence Questionnaire Short Form, occurrence of surgical retreatment, and freedom from complications. RESULTS AND LIMITATIONS: One hundred and thirty-six patients were treated using GL-XPS and 133 using TURP. Noninferiority of GL-XPS on International Prostate Symptom Score, Qmax, and freedom from complications was demonstrated at 6-mo and was sustained at 2-yr. The proportion of patients complication-free through 24-mo was 83.6% GL-XPS versus 78.9% TURP. Reductions in prostate volume and prostate specific antigen were similar in both arms and sustained over the course of the trial. Compared with the 1(st) yr of the study, very few adverse events or retreatments were reported in either arm. Treatment differences in the Overactive Bladder Questionnaire Short Form observed at 12-mo were not statistically significant at 24-mo. A limitation was that patients and treating physicians were not blinded to the therapy. CONCLUSIONS: Twenty-four-mo follow-up data demonstrated that GL-XPS provides a durable surgical option for the treatment of BPO that exhibits efficacy and safety outcomes similar to TURP. PATIENT SUMMARY: The long-term effectiveness and safety of GLP-XLS was similar to conventional TURP for the treatment of prostate enlargement.

Computer-aided transrectal ultrasound: does prostate HistoScanning™ improve detection performance of prostate cancer in repeat biopsies?

BACKGROUND: An imaging tool providing reliable prostate cancer (PCa) detection and localization is necessary to improve common diagnostic pathway with ultrasound targeted biopsies. To determine the performance of transrectal ultrasound (TRUS) augmented by prostate HistoScanning(TM) analysis (PHS) we investigated the detection of prostate cancer (PCa) foci in repeat prostate biopsies (Bx). METHODS: 97 men with a mean age of 66.2 (44-82) years underwent PHS augmented TRUS analysis prior to a repeat Bx. Three PHS positive foci were defined in accordance with 6 bilateral prostatic sectors. Targeted Bx (tBx) limited to PHS positive foci and a systematic 14-core backup Bx (sBx) were taken. Results were correlated to biopsy outcome. Sensitivity, specificity, predictive accuracy, negative predictive value (NPV) and positive predictive value (PPV) were calculated. RESULTS: PCa was found in 31 of 97 (32%) patients. Detection rate in tBx was significantly higher (p < .001). Detection rate in tBx and sBx did not differ on patient level (p ≥ 0.7). PHS sensitivity, specificity, predictive accuracy, PPV and NPV were 45%, 83%, 80%, 19% and 95%, respectively. CONCLUSIONS: PHS augmented TRUS identifies abnormal prostatic tissue. Although sensitivity and PPV for PCa are low, PHS information facilitates Bx targeting to vulnerable foci and results in a higher cancer detection rate. PHS targeted Bx should be considered in patients at persistent risk of PCa.

Reliability of dynamic sentinel node biopsy combined with ultrasound-guided removal of sonographically suspicious lymph nodes as a diagnostic approach in patients with penile cancer with palpable inguinal lymph nodes.

INTRODUCTION AND OBJECTIVES: Dynamic sentinel node biopsy (DSNB) is considered "unsuitable" in patients with penile cancer and palpable inguinal lymph nodes. The aim of this study was to determine the diagnostic reliability of DSNB combined with ultrasound (US)-guided removal of additional suspicious lymph nodes as a minimally invasive diagnostic approach in these patients. MATERIAL AND METHODS: A total of 23 consecutive patients with penile cancer and unilaterally or bilaterally palpable inguinal lymph nodes underwent DSNB according to the 2-day protocol. Before the combined staging procedure, the patients underwent preoperative US of both groins. During surgery, sentinel nodes and additional suspicious lymph nodes as determined by the US examination were removed under US guidance. A complete inguinal lymph node dissection was only performed in patients who had tumor-positive nodes. Follow-up consisted of control visits according to the European Association of Urology guidelines, including US investigation of the groins. RESULTS: The primary tumors were staged as T1, T2, and T3 carcinomas in 12, 8, and 3 patients, respectively. Grading was good, moderate, and poor in 2, 16, and 4 cases, respectively. Tumor grading could not be determined in 1 patient who underwent surgery of the invasive part of the primary tumor elsewhere. Sentinel nodes or nonsentinel nodes or both were positive in 15 of 36 palpatory-positive groins. DSNB alone showed lymphatic spread in 10 inguinal regions. US-guided removal of suspicious nonsentinel nodes revealed 5 further inguinal basins with metastases, which would have been missed by DSNB owing to rerouting or complete blockage of the lymphotropic tracer. So far, no lymph node relapse has been observed in the 12 patients with node-negative disease by this combined diagnostic approach with a median follow-up of 42 (16-84) months. The morbidity (postoperative bleeding and prolonged lymphorrhea) associated with this procedure was minor (6%). CONCLUSIONS: The results of this study imply that DSNB combined with US-guided removal of suspicious lymph nodes is a reliable diagnostic approach in patients with penile cancer with palpable inguinal lymph nodes. DSNB alone in these patients leads to a significant false-negative rate. These early and promising results have to be confirmed in larger cohort studies.

A European multicenter randomized noninferiority trial comparing 180 W GreenLight XPS laser vaporization and transurethral resection of the prostate for the treatment of benign prostatic obstruction: 12-month results of the GOLIATH study.

PURPOSE: We present the 1-year results of the GOLIATH prospective randomized controlled trial comparing transurethral resection of the prostate to GreenLight XPS for the treatment of men with nonneurogenic lower urinary tract symptoms due to prostate enlargement. The updated results at 1 year show that transurethral resection of the prostate and GreenLight XPS remain equivalent, and confirm the therapeutic durability of both procedures. We also report 1-year followup data from several functional questionnaires (OABq-SF, ICIQ-SF and IIEF-5) and objective assessments. MATERIALS AND METHODS: A total of 291 patients were enrolled at 29 sites in 9 European countries. Patients were randomized 1:1 to undergo GreenLight XPS or transurethral resection of the prostate. The trial was designed to evaluate the hypothesis that GreenLight XPS is noninferior to transurethral resection of the prostate on the International Prostate Symptom Score at 6 months. Several objective parameters were assessed, including maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen, in addition to functional questionnaires and adverse events at each followup. RESULTS: Of the 291 enrolled patients 281 were randomized and 269 received treatment. Noninferiority of GreenLight XPS was maintained at 12 months. Maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen were not statistically different between the treatment arms at 12 months. The complication-free rate at 1 year was 84.6% after GreenLight XPS vs 80.5% after transurethral resection of the prostate. At 12 months 4 patients treated with GreenLight XPS and 4 who underwent transurethral resection of the prostate had unresolved urinary incontinence. CONCLUSIONS: Followup at 1 year demonstrated that photoselective vaporization of the prostate produced efficacy outcomes similar to those of transurethral resection of the prostate. The complication-free rates and overall reintervention rates were comparable between the treatment groups.

180-W XPS GreenLight laser vaporisation versus transurethral resection of the prostate for the treatment of benign prostatic obstruction: 6-month safety and efficacy results of a European Multicentre Randomised Trial--the GOLIATH study.

BACKGROUND: The comparative outcome with GreenLight (GL) photoselective vaporisation of the prostate and transurethral resection of the prostate (TURP) in men with lower urinary tract symptoms due to benign prostatic obstruction (BPO) has been questioned. OBJECTIVE: The primary objective of the GOLIATH study was to evaluate the noninferiority of 180-W GL XPS (XPS) to TURP for International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax) at 6 mo and the proportion of patients who were complication free. DESIGN, SETTING, AND PARTICIPANTS: Prospective randomised controlled trial at 29 centres in 9 European countries involving 281 patients with BPO. INTERVENTION: 180-W GL XPS system or TURP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Measurements used were IPSS, Qmax, prostate volume (PV), postvoid residual (PVR) and complications, perioperative parameters, and reintervention rates. Noninferiority was evaluated using one-sided tests at the 2.5% level of significance. The statistical significance of other comparisons was assessed at the (two-sided) 5% level. RESULTS AND LIMITATIONS: The study demonstrated the noninferiority of XPS to TURP for IPSS, Qmax, and complication-free proportion. PV and PVR were comparable between groups. Time until stable health status, length of catheterisation, and length of hospital stay were superior with XPS (p<0.001). Early reintervention rate within 30 d was three times higher after TURP (p=0.025); however, the overall postoperative reintervention rates were not significantly different between treatment arms. A limitation was the short follow-up. CONCLUSIONS: XPS was shown to be noninferior (comparable) to TURP in terms of IPSS, Qmax, and proportion of patients free of complications. XPS results in a lower rate of early reinterventions but has a similar rate after 6 mo. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01218672.

Computer-aided (HistoScanning) biopsies versus conventional transrectal ultrasound-guided prostate biopsies: do targeted biopsy schemes improve the cancer detection rate?

OBJECTIVE: To define potential improvement in prostate cancer detection by application of a computer-aided, targeted, biopsy regimen using HistoScanning. MATERIALS AND METHODS: We analyzed 80 patients who underwent systematic transrectal, targeted transrectal, and targeted perineal biopsies. Each patient was diagnosed preoperatively by HistoScanning, defining a maximum of 3 suspicious areas. These areas were biopsied, both transrectally and via the perineum, with a maximum of 3 cores per location. RESULTS: We detected prostatitis in 30 patients (37.5%), premalignant lesions in 10 (12.5%), and prostate cancer in 28 (35%). The transrectal technique was used to detect 78.6% of all cancers using 14 cores by systematic biopsy. With a maximum of 9 targeted cores, 82.1% of all cancers were detected with the targeted perineal approach and 53.6% were detected with the targeted transrectal approach. Although our data did not show significant difference in the performance of targeted transperineal compared with systematic transrectal biopsies, the detection rate of targeted transrectal biopsies was significantly lower. CONCLUSION: The presented targeted biopsy scheme achieved an overall detection rate of 85% of prostate-specific antigen-relevant pathologic lesions within the prostate. Thus, the presented procedure shows an improved detection rate compared with standard systematic prostate biopsies, and the number of cores required is reduced. Furthermore, the perineal HistoScanning-aided approach seems to be superior to the transrectal approach with respect to the prostate cancer detection rate. The presented procedure might be a step toward reliable ultrasound-based tissue characterization and toward fulfilling the requirements of novel therapeutic strategies.