Tom Claeys

Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography-computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)-free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

Prevalence and prognosis of low-volume, oligorecurrent, hormone-sensitive prostate cancer amenable to lesion ablative therapy

To describe the anatomical patterns of prostate cancer (PCa) recurrence after primary therapy and to investigate if patients with low‐volume disease have a better prognosis as compared with their counterparts.

Salvage pelvic lymph node dissection in recurrent prostate cancer: surgical and early oncological outcome

Methodology. Seventeen patients with prostate-specific antigen (PSA) rise following local treatment for prostate cancer with curative intent underwent open or minimally invasive salvage pelvic lymph node dissection (SLND) for oligometastatic disease (<4 synchronous metastases) or as staging prior to salvage radiotherapy. Biochemical recurrence after complete biochemical response (cBR) was defined as 2 consecutive PSA increases >0,2 ng/mL; and after incomplete biochemical response as 2 consecutive PSA rises. Newly found metastasis on imaging defined clinical progression (CP). Palliative androgen deprivation therapy (ADT) was initiated if >3 metastases were detected or if patients became symptomatic. Kaplan-Meier statistics were applied. Results. Clavien-Dindo grade 1, 2, 3a, and 3b complications were seen in 6, 1, 1, and 2 patients, respectively. Median follow-up time was 22 months. Among 13 patients treated for oligometastatic disease, 8 (67%) had a PSA decline, with 3 patients showing cBR. Median PSA progression-free survival (FS) was 4.1 months and median CP-FS 7 months. Three patients started ADT, resulting in a 2-year ADT-FS rate of 79.5%. Conclusion. SLND is feasible, but postoperative complication rate seems higher than that for primary LND. Biochemical and clinical response duration is limited, but as part of an oligometastatic treatment regime it can defer palliative ADT.

Urodynamic studies in children: Standardized transurethral video-urodynamic evaluation

OBJECTIVE The aim was too demonstrate standardized video-urodynamic study (VUDS) in children using a transurethral catheter and pressure transducers. METHODS Data necessary to obtain urodynamic evaluation of bladder sphincter function were gathered by concomitant measurement of bladder, urethral, and abdominal pressure. A 7F transurethral triple-lumen water-filled catheter was used for measuring the bladder and sphincter pressures and a water-filled 8F catheter connected to a pressure transducer was inserted into the rectum for pressure measurement. Cystometry was combined with fluoroscopy, providing simultaneous voiding cystourethrography information. Detrusor activity, bladder sensation, capacity, and compliance were measured during filling cystometry. Voiding cystometry consisted of recording pressures in the bladder sphincter and abdomen with simultaneous urinary flow measurement. RESULTS Transurethral VUDS was safely and easily performed in a clinical setting adapted to children. CONCLUSIONS A good and reproducible UDS is mandatory for correct therapeutic decisions. A standardized study associated with fluoroscopic assessment is presented in this video.

Isolated Male Epispadias: Anatomic Functional Restoration Is the Primary Goal.

Background. Isolated male epispadias (IME) is a rare congenital penile malformation, as often part of bladder-exstrophy-epispadias complex (BEEC). In its isolated presentation, it consists in a defect of the dorsal aspect of the penis, leaving the urethral plate open. Occurrence of urinary incontinence is related to the degree of dorsal displacement of the meatus and the underlying underdevelopment of the urethral sphincter. The technique for primary IME reconstruction, based on anatomic restoration of the urethra and bladder neck, is here illustrated. Patients and Methods. A retrospective database was created with patients who underwent primary IME repair between June 1998 and February 2014. Intraoperative variables, postoperative complications, and outcomes were assessed. A descriptive statistical analysis was performed. Results and Limitations. Eight patients underwent primary repair, with penopubic epispadias (PPE) in 3, penile epispadias (PE) in 2, and glandular epispadias (GE) in 3. Median age at surgery was 13.0 months [7–47]; median follow-up was 52 months [9–120]. Complications requiring further surgery were reported in two patients, while further esthetic surgeries were required in 4 patients. Conclusion. Anatomical restoration in primary IME is safe and effective, with acceptable results given the initial pathology.

Comparison of the Prostate Imaging Reporting and Data System (PI-RADS) Version 1 and 2 in a Cohort of 245 Patients with Histopathological Reference and Long Term Follow-Up.

Objective: To compare the performance of PI-RADSv2 with PI-RADSv1 in patients with elevated PSA before biopsy. Methods: 245 patients with elevated PSA underwent mpMRI before biopsy between May 2011 and December 2014 at 3.0 Tesla without endorectal coil. Patients underwent transrectal ultrasound-guided systematic 12-core biopsy followed by radical prostatectomy (N = 68), radiation therapy (N = 91) or clinical follow-up for at least two years (N = 86). All exams were scored on a per-patient basis according to PI-RADSv1 and PI-RADSv2. ClinsigPC was defined as Gleason score ≥7 (including 3+4 with prominent but not predominant Gleason 4 component), and/or tumour volume of ≥0.5cc, and/or tumour stage ≥T3a. Results: In 144 patients (58.8%) a ClinsigPC was found within two years after mpMRI. The PI-RADSv1 and PI-RADSv2 overall assessment scores were significantly higher (P < 0.001) in patients with ClinsigPC as compared to patients without ClinsigPC. ROC analysis showed an area under the curve of 0.82 (CI 0.76–0.87) for PI-RADSv1 and 0.79 (CI 0.73–0.85) for PI-RADSv2 (P: NS). A threshold score of 3 exhibited sensitivities of 88.2% and 79.2% (P = 0.001) and specificities of 64.4% and 67.3% (P: NS) with PI-RADSv1 and PI-RADSv2, respectively. Conclusions: The mpMRI scoring systems PI-RADSv1 and PI-RADSv2 yield similar accuracy to detect ClinsigPC in patients with elevated PSA, although clinicians should be aware that when an overall assessment score of 3 is used as a threshold for a positive mpMRI, PI-RADSv2 has lower sensitivity than PI-RADSv1. Nevertheless, PI-RADSv2 is preferable over PI-RADSv1 because it has the advantage of providing well-defined instructions on how to determine the overall assessment category.

The independent oncological role for cytoreductive nephrectomy in metastatic renal cell carcinoma: Prognostic features in the era of targeted therapies

OBJECTIVES To describe the effects of cytoreductive nephrectomy (CN) on the natural course of metastatic renal cell carcinoma (mRCC). CN appears to stabilize metastatic lesions in mRCC in a subgroup of patients and we hypothesize that systemic treatment might be deferred in these patients with stable disease after CN. SUBJECTS AND METHODS Overall, 45 patients with mRCC who underwent CN and subsequent oncologic follow-up were included in this retrospective, single-center analysis. After CN, patients were followed at least every 3 months with clinical evaluation, contrast-enhanced computerized tomography scan of chest and abdomen, with additional imaging if needed. At 3 months, patients were radiographically evaluated and categorized into nonresponders (death or progression) or responders (stable disease or remission). Kaplan-Meier and Cox proportional hazards regression statistics were used to describe prognostic factors for overall survival (OS) and systemic therapy-free survival (STFS). RESULTS Median OS was 31(3-121) months. Further, 24 (53.3%) and 21 (46.7%) patients were classified as responders and nonresponders at 3 months, respectively. Responders had a significant better 2-year OS compared with nonresponders (81.7% vs. 26.5%, P = 0.005). Responders also had a better 2-year STFS (40.3% vs. 6.3%, P = 0.005). On Cox regression analysis, worse OS was found to be associated with low preoperative hemoglobin levels, the absence of postoperative radiographical response, and the presence of non-clear cell pathology. The presence of postoperative radiographical response, normal preoperative lactate dehydrogenase levels, the presence of a single metastasis, and performing metastasis-directed therapy was found to be associated with a longer systemic therapy-free period. CONCLUSION A beneficial oncologic response is observed in approximately half of the patients undergoing CN. Absence of radiographic progression at 3 months is an important marker for OS and STFS. Therefore, systemic treatment might be postponed in selected patients.

Androgen Receptor Gene Copy Number and Protein Expression in Treatment-Naïve Prostate Cancer.

Objectives: To evaluate the androgen receptor (AR) gene copy number in androgen deprivation therapy (ADT) treatment-naïve prostate cancer (PCa) patients and to evaluate the corresponding AR protein expression and assess the association between these features and prognostic factors. Materials and Methods: Chromosome X and AR gene copy number, using fluorescence-in-situ-hybridization, and epithelial-stromal AR expression, using AR immunohistochemistry, were analyzed in 62 ADT treatment-naïve PCa patients and 8 castration-refractory patients. Results: In ADT treatment-naïve PCa patients, the AR expression was higher in tumor epithelial cells versus surrounding stromal cells (p < 0.001) and versus normal epithelium in the same patient (p = 0.043). The difference between tumoral AR expression and expression in normal epithelium was higher in patients with ≥15% of tumor cells with increased AR copy number (p = 0.019). Peritumoral stroma had lower AR expression in patients with lymph-node or distant metastases compared to those without metastases (p = 0.038). Conclusions: This research evaluates the link between AR gene status, expression profile, and possible prognostic factors. Furthermore, it highlights the importance of the peritumoral environment in PCa. Additional research is needed to further clarify the role of stromal AR in PCa dissemination and identify possible therapeutic strategies to target this mechanism.

Genitoplasty in newborn females with adrenogenital syndrome : focus on the reconstruction technique and its outcomes

The adrenogenital syndrome is an autosomal recessive disorder in which an enzyme defect in the steroid pathway leads to excessive prenatal exposure of androgens. In the female fetus, masculinization of the external genitalia is observed. Surgery aims for functional and aesthetical reconstruction. Many techniques have been described. A video of our modified pull-through reconstruction technique is hereby presented. A retrospective descriptive database was created with patients who underwent genitoplasty for a CAH-associated genital condition. A video demonstrating the reconstructive technique was recorded while operating on a 9-month-old girl. Prior to surgery a cystoscopy is performed to evaluate the length of the urogenital sinus. Surgery starts with creating a reversed U-flap, after which the urogenital sinus is mobilized. The corpora cavernosa are released and the neurovascular bundle is isolated. To create vaginal space the urogenital sinus is subsequently separated. The vaginal introitus is anchored to the perineal skin flap. Labia minora are created by splitting the preputial skin. Finally excessive skin tissue is resected. Twenty-two female patients underwent reconstructive surgery for the adrenogenital syndrome in a tertiary referral centre over 16 years. Median age at surgery was 3 months (0-190). Median follow-up was 36 months (0-108) after surgery. A good functional and aesthetical outcome was observed. The modified pull-through technique, illustrated by this video, provided satisfactory results with a low complication rate. Follow-up until adulthood is needed to evaluate long-term outcomes.

Prognostic and therapeutic implications of circulating androgen receptor gene copy number in prostate cancer patients using droplet digital polymerase chain reaction

&NA; Because resistance mechanisms in the androgen receptor (AR) pathway remain key drivers of progression, we assessed the AR gene copy number (CN) gain in a general population (n = 100) and its implications in prostate cancer. AR CN gain was found to be a promising biomarker anticipating faster progression to castration‐resistant prostate cancer (CRPC), a poor prognosis, and worse abiraterone and enzalutamide outcomes in CRPC. Background: Resistance mechanisms in the androgen receptor (AR) signaling pathway remain key drivers in the progression to castration‐resistant prostate cancer (CRPC) and relapse under antihormonal therapy. Materials and Methods: We evaluated the circulating AR gene copy number (CN) gain using droplet digital polymerase chain reaction in 21 control and 91 prostate cancer serum samples and its prognostic and therapeutic implications in prostate cancer. Results: In CRPC, AR CN gain was associated with faster progression to CRPC (P = .026), a greater number of previous treatments (P = .045), and previous chemotherapy (P = .016). Comparing patients with and without CN gain, the median progression‐free survival (PFS) in the abiraterone subgroup was 1.7 months versus not reached (P = .004), and the median overall survival (OS) was 7 months versus 20.9 months (P = .020). In the enzalutamide subgroup, PFS was 1.7 versus 10.8 months (P = .006), and OS was 6.1 versus 16.5 months (P = .042). In the taxane subgroup, PFS was 3.2 versus 6.5 months (P = .093), and OS was 3.9 months versus not reached (P = .026). The presence of more AR copies correlated with shorter androgen deprivation (P = .002), abiraterone (P = .022), enzalutamide (P = .008), and taxane (P = .039) therapy. Conclusion: Circulating AR CN gain predicts for a poor prognosis in CRPC. It is a promising biomarker predetermining rapid CRPC progression and predicting worse abiraterone and enzalutamide outcomes. Furthermore, it is associated with multiple previous treatments and previous chemotherapy.