Therapeutic Advances in Urology

Mastering bladder paraganglioma for optimal treatment: a case report of robot-assisted surgery
Orsini A, Ferretti S, Tamborino F, Cicchetti R, Ciavarella D, Seccia B, Basilico R, Colasante A, Marchioni M and Schips L
Bladder paraganglioma is a rare neuroendocrine neoplasm, either functional or non-functional, arising from the urinary bladder. Functional variants present with catecholamine-related symptoms, while non-functional variants pose diagnostic challenges, mimicking urothelial carcinoma. Misdiagnosis risks underscore the importance of accurate identification for appropriate patient management. In this case, a 52-year-old man, diagnosed incidentally with hypertension and reported occasional post-micturition tachycardia, underwent abdominal ultrasound for known hepatic cyst follow-up, revealing an oval hypoechoic bladder mass. Initial consideration of bladder urothelial carcinoma prompted further investigation with contrast-enhanced CT scan and cystoscopy that confirmed extrinsic mass nature, and subsequent robotic-assisted partial cystectomy was performed. Histologically, the removed mass exhibited characteristic features of bladder paraganglioma. Postoperative recovery was uneventful, with resolution of post-micturition tachycardia at 1 month. Follow-up includes endocrinological evaluation and a 6-month CT scan. In conclusion, bladder paraganglioma should be considered in para-vesical mass differentials. This case highlights the importance of meticulous history collection, even in asymptomatic patients, the need for a multidisciplinary approach for accurate diagnosis and management of this rare condition, and the robotic approach as a viable option.
Long-term impact of commonly performed operations in pediatric urology on reproductive and sexual health
Geada A, Jivanji D, Tennenbaum DM, Ghomeshi A, Reddy R, Sencaj M, Thomas J, Nassau DE and Ramasamy R
Sexual dysfunction is highly prevalent among men of reproductive age. Clinical practice guidelines have been established to assist providers in identification and education of patients who are at increased risk for infertility and sexual dysfunction with certain congenital and acquired urogenital disorders. The authors sought to review the reproductive and sexual health implications of treating common childhood urological conditions with commonly performed surgical procedures.
Prostatic stents: a narrative review of current evidence
Cerrato C, Antoniou V, Napolean Fernandes S, Madaan S and Somani BK
Benign prostatic hyperplasia (BPH) is a common chronic urologic condition affecting approximately 50% of men above the age of 60. As per European Association of Urology Guidelines, BPH can be treated according to a stepwise approach starting from a conservative management, a pharmacologic approach, and finally surgery. Both medical and surgical therapies have side effects, impacting on ejaculation and sexual function and patients with multiple comorbidities might not be considered surgically suitable candidates. Prostatic stents offer a minimally invasive procedures in an out-patient setting, possibly under local anaesthesia. Utilized since the 1980s, the past stents encompassed permanent (epithelializing) or temporary (non-epithelializing) devices, like the Uro-Lume (American Medical Systems, Minnetonka, MN, USA) and the Memokath, or Memotherm (Engineers & Doctors A/S, Denmark), and the biodegradable stents made of self-reinforced poly-L-lactide or braided poly lactic-co-glycolic acid. Previous stents however showed a quite high rate of complications among which pain, incontinence, infections, stent migration or blockage, and incomplete degradation that might lead to premature removal of stent. The stents currently available on the market instead are the temporary device Allium Triangular Prostatic Urethral Stent (Allium Urological Solutions, Caesarea, Israel) and the temporary stent SPANNER (AbbeyMoor Medical, Inc., Parkers Prairie, MN, USA), which might be used in case of bladder outflow obstruction, post-operatively, or for acute urinary retention. Studies showed encouraging results, in terms of effectiveness and safety improving patients' quality of life and International Prostate Symptom Score, but longer-term studies are needed to identify the most suitable patients who might benefit from their use. Newer stents and nitinol devices are currently investigated, and we are waiting for the results of the ongoing clinical trials.
Systematic review of recent advancements in antibody-drug and bicycle toxin conjugates for the treatment of urothelial cancer
Domb C, Garcia JA, Barata PC, Mendiratta P, Rao S and Brown JR
Antibody-drug conjugates and bicycle toxin conjugates represent a tremendous advance in drug delivery technology and have shown great promise in the treatment of urothelial cancer. Previously approved systemic therapies, including chemotherapy and immunotherapy, are often impractical due to comorbidities, and outcomes for patients with advanced disease remain poor, even when receiving systemic therapy. In this setting, antibody-drug and bicycle toxin conjugates have emerged as novel treatments, dramatically altering the therapeutic landscape. These drugs harness unique designs consisting of antibody or bicycle peptide, linker, and cytotoxic payload with more targeted delivery than conventional chemotherapy, thus eliminating malignant cells while reducing systemic toxicities. Potential targets investigated in urothelial cancer include Nectin-4, TROP2, HER2, and EphA2. Initial clinical trials demonstrated efficacy in treatment of refractory advanced urothelial cancer, as well as improvement in quality of life. These initial studies led to FDA approval of two antibody-drug conjugates, enfortumab vedotin and sacituzumab govitecan. Moreover, antibody-drug and bicycle toxin conjugates are being studied in ongoing clinical trials in frontline treatment of advanced disease as well as for localized cancer. These studies highlight the potential for additional future therapies with novel targets, novel antibodies, cytotoxic and immunomodulatory payloads, and unique structural designs enhancing efficacy and safety. There is increasing evidence that combinations with other cancer therapies, especially immunotherapy, improve treatment outcomes. The combination of enfortumab vedotin and pembrolizumab was recently approved for first-line treatment of advanced urothelial carcinoma. Despite the great promise of these novel drugs, robust predictive biomarkers are needed to determine the patients who would maximally benefit. This review surveys the rationale and current state of the evidence for these new drugs and describes future directions actively being explored.
A multi-institutional update on surgical outcomes after penile silicone sleeve implantation
Siegal AR, Celtik KE, Razdan S, Sljivich M, Kansas B, Shah B, Levine LA and Valenzuela RJ
The increasing popularity of the silicone sleeve penile implant has been accompanied by concerns over potential risks and adverse events.
Testosterone suppression and recovery in patients with advanced prostate cancer treated with intermittent androgen deprivation therapy with relugolix
Campbell P, Gebrael G, Narang A, Chehade CH, Thomas VM, Galarza Fortuna G, Sayegh N, Tripathi N, Tandar C, Dal E, Li H, Swami U, Agarwal N and Maughan BL
Intermittent androgen deprivation therapy (iADT) may result in measurable improvements in quality of life over continuous ADT in patients with advanced prostate cancer (aPC). Here, we studied time to castration and testosterone recovery in real-world patients with aPC undergoing iADT with relugolix.
Effect of surgical, medical, and behavioral weight loss on hormonal and sexual function in men: a contemporary narrative review
Santamaria A, Amighi A, Thomas M, Goradia R, Choy J and Hehemann MC
This review explores the mechanisms and ramifications of weight loss achieved through lifestyle modifications, medical treatments, and bariatric surgery on testosterone levels and sexual health. Obesity significantly affects the hypothalamic-pituitary-gonadal axis in men, leading to diminished libido and erectile dysfunction. Here, we delve into the physiological disruptions caused by this imbalance and the intricate interplay of hormonal factors contributing to the dysregulation associated with obesity to comprehensively grasp the consequences of weight loss via diverse mechanisms. Lifestyle modifications involving dietary adjustments and regular exercise represent a widely employed and efficacious means of weight loss. While adherence demands discipline, our review scrutinizes various studies specifically investigating the impact of weight loss, attained through lifestyle modifications, on serum hormone levels and sexual function. Notably, several randomized controlled trials within the existing body of literature corroborate the enhancement of testosterone levels and sexual function consequent to weight loss through lifestyle modifications. The realm of medical management in addressing obesity is growing, notably propelled by the popularity of pharmacotherapy. Despite its prevalence, the current literature exploring the effects of weight loss medications on men remains insufficient. Nonetheless, we examine available studies on the medical management of obesity and its implications for sexual health, emphasizing pivotal avenues requiring further investigation. Bariatric surgery stands as an effective approach for individuals seeking substantial weight loss. Our review assesses existing literature that evaluates the impact of various surgical techniques on serum hormone levels, sexual function, and semen parameters. Despite certain limitations, the available body of evidence suggests enhancements in hormone levels and sexual function post-surgery, with semen parameters generally exhibiting minimal changes. This review critically evaluates the landscape of weight loss and its correlation with sexual function, while highlighting crucial areas necessitating future research endeavors.
A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product
Bernstein JS and Dhingra OP
Oral testosterone undecanoate (TU) formulations may provide effective, safe, and easily titratable testosterone replacement therapy.
Meta-analysis of postoperative urinary incontinence incidence and risk factors in HoLEP
Yang M, Huang Y, Gao F, He L, Yu X and Yu Q
To systematically identify and quantify the incidence and risk factors of postoperative urinary incontinence (UI) in holmium laser enucleation of the prostate (HoLEP), aiming to provide a basis for intervention strategies.
Clinical use of nadofaragene firadenovec-vncg
Konety BR, Shore ND and Sant GR
Non-muscle-invasive bladder cancer (NMIBC), which is restricted to the mucosa (stage Ta, carcinoma in situ (CIS)) or submucosa (stage T1), comprises 75% of bladder cancer diagnoses. Intravesical bacillus Calmette-Guérin (BCG) therapy is the standard-of-care initial treatment for high-risk NMIBC; however, a significant proportion of patients have BCG-unresponsive disease. While radical cystectomy is a definitive treatment in this setting, not all patients are willing or able to undergo this complex procedure associated with morbidity, mortality, and decreased quality of life. Bladder-preserving options for patients with BCG-unresponsive NMIBC represent an unmet need in this patient population. Nadofaragene firadenovec-vncg (Adstiladrin) is a nonreplicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors. The antitumor efficacy of nadofaragene firadenovec is driven by its local delivery of copies of the gene encoding for interferon alpha-2b (IFNα-2b) to urothelial cells. In the phase III CS-003 study, over half of participants with CIS exhibited a complete response by month 3 after instillation, with minimal serious adverse events. The favorable efficacy and safety profile, clinical utility, novel mechanism of action, and every 3-month dosing schedule give nadofaragene firadenovec a unique role in the treatment of high-risk BCG-unresponsive NMIBC. This review provides a practical approach to the effective clinical use of nadofaragene firadenovec regarding pre-instillation visit arrangements, storage, handling, instillation procedures, and post-instillation procedures. Implementation of these recommendations will ensure efficient real-world use of nadofaragene firadenovec and the development of useful training materials and relevant standard operating procedures to help support a clinic's treatment for patients with BCG-unresponsive NMIBC with CIS. Video Abstract https://vimeo.com/user17898099/review/953723559/e18af7ec43.
Characterizing patient experiences with repeat artificial urinary sphincter revisions through quantitative surveys and qualitative patient interviews
Huffman PJ, Ewachiw G, Johnson R, Huang MM, Dani H, Knijnik PG, da Silva AF, Burnett AL, Mostwin JL, Wright EJ and Cohen AJ
Artificial urinary sphincter (AUS) placement remains the gold-standard treatment for post-prostatectomy urinary incontinence (PPUI), despite their need for periodic surgical revision.
Outcomes and patient satisfaction after Penuma silicone implant surgery via two surgical approaches
Salkowski M and Levine LA
The Penuma is a soft silicone penile implant designed for cosmetic enhancement of the flaccid penis in men who have normal erections.
A machine learning-based nomogram model for predicting the recurrence of cystitis glandularis
Liu X, Wang Y, Wang Y, Dao P, Zhou T, Zhu W, Huang C, Li Y, Yan Y and Chen M
Cystitis glandularis is a chronic inflammatory disease of the urinary system characterized by high recurrence rates, the reasons for which are still unknown.
Assessing the effectiveness and safety of lenvatinib and everolimus in advanced renal cell carcinoma: insights from the RELIEVE study's analysis of heavily pretreated patients
Buti S, Olivari A, Masini C, Bimbatti D, Sartori D, Ermacora P, Cattrini C, Vitale MG, Rossi E, Mucciarini C, Rizzo M, Sisani M, Santoni M, Roviello G, Mollica V, Conteduca V, Grillone F, Cinausero M, Prati G, Atzori F, Stellato M, Massari F and Bersanelli M
The treatment of heavily pretreated patients with metastatic renal cell carcinoma (mRCC) represents an unmet medical need and is still challenging.
PARP inhibitors alone or in combination for prostate cancer
Fenor de la Maza MD, Pérez Gracia JL, Miñana B and Castro E
DNA repair genomic aberrations in the Homologous Recombination pathway are identifiable in up to 25% of patients with advanced prostate cancer, making them more likely to benefit from treatment with poly (ADP-ribose) polymerase inhibitors (PARPi) alone or in combination with other therapies, particularly when BRCA driver genomic aberrations are documented. Although several clinical trials have demonstrated the efficacy of this approach, the validation of reliable biomarkers predictive of response still needs further improvement to refine patient selection. In this setting, the characterization of resistance mechanisms and the validation of novel biomarkers are critical to maximize clinical benefit and to develop novel treatment combinations to improve outcomes. In this review, we summarize the development of PARPi in prostate cancer as single agent as well as the efficacy of their combination with other drugs, and the future directions for their implementation in the management of advanced prostate cancer.
Meta-analysis of perioperative outcomes and safety of percutaneous nephrostomy retrograde ureteral stenting in the treatment of acute obstructive upper urinary tract infection
Wang X, Wu G, Wang T, Liu S, Ding G, Mao Q, Chu Y, Cui Y and Wu J
The debate regarding the optimal drainage method for acute obstructive upper urinary tract infection persists, focusing on the choice between percutaneous nephrostomy (PCN) and retrograde ureteral stenting (RUS).
Comparison of ureteoroscopy and laser stone fragmentation between Holmium: YAG laser with MOSES versus non-MOSES technology: a prospective single-center propensity score-matched analysis using similar laser settings
Jahrreiss V, Ripa F, Cerrato C, Nedbal C, Pietropaolo A and Somani B
In vitro studies have shown that the holmium Modulated Optics Enhancement Systems (MOSES) technology can lead to an increase in the efficacy of lithotripsy and a reduction of retropulsion, but clinical evidence comparing it to non-MOSES technology is still scarce. We did a comparison of ureteoroscopy and laser stone fragmentation (URSL) between Holmium:YAG laser with MOSES versus non-MOSES technologies.
Treatment modalities for paediatric functional daytime lower urinary tract disorders: an updated review
Wijekoon N and Deshpande A
Paediatric functional bladder disorders especially those causing daytime symptoms are a common cause of significant psychosocial and/or physical morbidity and impaired quality of life. Despite the availability of many therapeutic modalities, a significant number of children appear to be refractory to treatment and continue to have symptoms. In this review, we aim to evaluate the current evidence in the use of existing and novel therapeutic options for the management of daytime lower urinary tract disorders in children. We also aim to highlight the controversies around the terminology and diagnosis of paediatric lower urinary tract dysfunction (LUTD) and specific conditions. The article will then provide a reasonable critique of the existing and emerging treatment modalities in functional daytime LUTD in children including their mode of action, efficacy, indications, and recent advances. These include standard urotherapy, specific urotherapy comprised of biofeedback, alarm therapy and electrical neural stimulation and pharmacotherapy involving selective and non-selective anticholinergics, ß adrenergic agonists, alpha blockers and botulinum toxin. A better understanding of this common clinical problem may help clinicians achieve better profiling of these children's diagnoses to further enable specific, targeted treatment.
Outcomes of ureteroscopy and laser fragmentation using a 60 W MOSES laser: a 3-year prospective study from a University Teaching Hospital
Jahrreiss V, Ripa F and Somani B
Modulated optics enhancement system (MOSES) holmium lasers use "pulse modulation" to increase the efficacy of laser lithotripsy. As the clinical evidence on the efficacy of 60 W holmium laser with MOSES technology is scarce, we analyzed the outcomes of patients treated with this laser at our institution.
Targeted augmented reality-guided transperineal prostate biopsies study: initial experience
Theivendrampillai S, Yang B, Little M and Blick C
Transperineal biopsy of magnetic resonance imaging (MRI)-detected prostate lesions is now the established technique used in prostate cancer (CaP) diagnostics. Virtual Surgery Intelligence (VSI) Holomedicine by Apoqlar (Hamburg, Germany) is a mixed reality (MR)/augmented reality (AR) software platform that runs on the HoloLens II system (Microsoft, Redford, USA). Multiparametric prostate MRI images were converted into 3D holograms and added into a MR space, enabling visualization of a 3D hologram and image-assisted prostate biopsy.
Prognostic factors and treatment choice for stage IV, low-volume metastasis hormone-sensitive prostate cancer: cross-sectional study of real-world data
Elewaily MI, Campione M, Hassan MA, Anpalakhan S, Atsumi N, Smalley B, Ashraf A, Gale J, Maniam A and Banna GL
Many metastatic prostate cancer prognostics have been suggested, but few are validated. Nodal metastasis burden and baseline biochemical characteristics are overlooked in the currently accepted stratifications for metastatic hormone-sensitive prostate cancer (mHSPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is likely to increase the incidence of pelvic nodal and mHSPC undetected by conventional scans. However, there is no consensus on managing regional nodal metastasis (N1M0) and no separate guidelines for non-regional nodal (M1a) and low-volume bone (M1b) spread but collectively as a part of low-volume CHAARTED disease.