3D printed patient-specific prostate cancer models to guide nerve-sparing robot-assisted radical prostatectomy: a systematic review.

Precise knowledge of each patient's index cancer and surrounding anatomy is required for nerve-sparing robot-assisted radical prostatectomy (NS-RARP). Complementary to this, 3D printing has proven its utility in improving the visualisation of complex anatomy. This is the first systematic review to critically assess the potential of 3D printed patient-specific prostate cancer models in improving visualisation and the practice of NS-RARP. A literature search of PubMed and OVID Medline databases was performed using the terms "3D Printing", "Robot Assisted Radical Prostatectomy" and related index terms as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eight articles were included; six were identified via database searches, to which a further two articles were located via a snowballing approach. Eight papers were identified for review. There were five prospective single centre studies, one case series, one technical report and one letter to the editor. Of these articles, five publications (62.5%) reported on the utility of 3D printed models for NS-RARP planning. Two publications (25%) utilised 3D printed prostate models for simulation and training, and two publications (25%) used the models for patient engagement. Despite the nascency of the field, 3D printed models are emerging in the uro-oncological literature as a useful tool in visualising complex anatomy. This has proven useful in NS-RARP for preoperative planning, simulation and patient engagement. However, best practice guidelines, the future regulatory landscape, and health economic considerations need to be addressed before this synergy of new technologies is ready for the mainstream.

Interrogating the Impassable: A Case Series and Literature Review of Unilateral SPECT-CT Groin Visualization in Men With Penile Cancer.

Penile squamous cell carcinoma (SCC) is a rare malignancy, which is known to invade local inguinal lymph nodes prior to progressing to the pelvis. Dynamic sentinel lymph node biopsy (DSLNB) is a standard for the minimally invasive assessment of lymphadenopathy in patients with subclinical groin metastasis. Hybrid 99mTc Single-Photon Emission Computed Tomography (SPECT-CT) has been shown to increase the accuracy of identifying first draining "sentinel" nodes (SN). Unilateral inguinal visualization on SPECT-CT is a rare presentation, which may increase the likelihood of a false negative SN biopsy. Retrospective analysis from three-penile cancer uro-oncologists in Melbourne, Australia identified 78 groins undergoing DSLNB for intermediate/high risk primary disease. Unilateral SPECT-CT results were observed in four patients suggesting a functional pattern of lymph diversion. Analysis confirmed malignancy (n = 2), sarcoidosis (n = 1), and evidence of local inflammation in SPECT-CT negative groins. Findings re-iterate the role of SPECT-CT a pre-operative adjunct. Experienced multimodal groin assessment using palpation, SPECT-CT, lymphoscintigraphy, and blue dye tracking remains paramount. Unilateral SN on pre-operative SPECT-CT in men with intermediate/high-risk penile SCC should elicit a higher degree of clinical suspicion. We recommend a low threshold for recommending radical inguinal lymph node dissection (ILND) for groins refractory to minimally invasive assessment.

Dynamic Sentinel Lymph Node Biopsy for Penile Cancer: Accuracy is in the Technique.

OBJECTIVES: To demonstrate an operative standard for dynamic sentinel lymph node biopsy (DSLNB). Long-term survival in men with penile squamous cell carcinoma (SCC) depends on accurately staging lymph node metastases. European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) guidelines recognize DSLNB as a standard for staging men with intermediate to high-risk tumors and clinically absent inguinal lymphadenopathy. DSLNB accuracy has been linked with pre-operative planning and surgical technique, yet no peer-reviewed video exists to establish an operative standard. Here we present a narrated video of our technique and discuss the accuracy of this approach using retrospective patient data. METHODS: Ethics approval and patient consent was obtained. Retrospective analysis was performed on patients undergoing DSLNB for inguinal lymph node staging of histologically proven penile SCC. Data was included from 2 experienced uro-oncologists with subspecialty training in penile cancer working in Victoria, Australia between January 2015 and July 2021. Variables collected included Primary tumour histology, DSLNB pathology, progression to radical inguinal lymph node dissection (RILND) and recurrence patterns. DSLNB sensitivity and proportion of groins spared RILND is calculated. RESULTS: DSLNB was performed on 127 groins (64 patients) during the study period. Within the cohort, 44% (n = 28) of patients had a pre-operative lymphoscintigraphy with single-photon emission computed tomography (SPECT/CT). Analysis of primary tumor intervention demonstrates that 82.8% (n = 53) of men underwent penile sparing surgery. Tumor histology in 88% of patients (n = 56) demonstrated pT1-pT2 disease. Overall n = 19 groins undergoing DSLNB were positive for malignancy and n = 108 were negative. 36 groins progressed to RILND during a mean follow up of 29 months. Only 2 groins that previously had a negative DSLNB were positive on RILND, one in the groin and one in the pelvis. We observed a false negative rate of 1.9% and a sensitivity of 90.5%. In our cohort DSLNB allowed 71.7% of groins to proceed for surveillance instead of prophylactic radical ILND. CONCLUSIONS: DSLNB is a safe and accurate method for assessing inguinal lymphadenopathy in men with intermediate to high-risk penile SCC and impalpable groins. This video study establishes an operative standard for DSLNB with oncological outcomes are consistent with international expectations. Standardized use of DSLNB by an experienced team will reduce morbidity while maintaining oncological safety for men with intermediate to high-risk penile cancer and cN0 disease.

Molecular and genomic characterisation of a panel of human anal cancer cell lines.

Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.

Clinical trials in urological oncology: COVID-19 and the potential need for a new perspective.

The COVID-19 pandemic has led to the suspension, termination or alteration of thousands of clinical trials as the health emergency escalated globally. Whilst the rapid suspension of certain clinical trials was necessary to ensure the safety of high-risk or vulnerable trial participants as well as healthcare workers, the long-term ramifications that this delay will have on the field of urologic oncology is unknown. The COVID-19 pandemic has highlighted the need to plan for and implement new strategies to advance our understanding of unmet areas of need in urologic oncology. The COVID-19 pandemic has led to the suspension, termination or alteration of thousands of clinical trials as the health emergency escalated globally. Whilst the rapid suspension of certain clinical trials was necessary to ensure the safety of high-risk or vulnerable trial participants as well as healthcare workers, the long-term ramifications that this delay will have on the field of urologic oncology is unknown. The COVID-19 pandemic has highlighted the need to plan for and implement new strategies to advance our understanding of unmet areas of need in urologic oncology.

Future directions in advanced penile cancer - mechanisms of carcinogenesis and a search for targeted therapy.

Penile squamous cell carcinoma (SCC) is a rare and aggressive urological malignancy. Advanced penile SCC requires multimodal management, including surgery and systemic therapy. Given its rarity, there have been few substantial advances in our understanding of the molecular and genomic drivers of penile SCC, especially for patients with relapsed or advanced disease. In this review, we discuss the molecular and genomic landscape of penile SCC, clinical trials in progress and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a platform for investigation and validation of new molecular pathways for testing of therapeutics.

Pitfalls of FDG-PET in the prostate for the surgical oncologist.

A 78-year-old man was referred for investigation of prostate cancer following incidental uptake on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Despite normal PSA and benign digital rectal exam, he was referred for consideration of trans-perineal biopsy to exclude prostate cancer. It was only on review of imaging that it became clearly apparent that the 18F-FDG uptake was due to urinary tracer pooling in a trans-urethral resection cavity. Surgeons, oncologists and nuclear medicine physicians should be aware of this common pitfall in interpretation of 18F-FDG-PET in the prostate.

Robot-assisted ipsilateral ureteroureterostomy in a duplex system utilizing intraoperative flexible ureteroscopy.

Iatrogenic injury to the ureter during pelvic surgery is an uncommon but well-documented complication. Accurate identification of the ureter during pelvic surgery is made far more complex in the presence of a duplex or ectopic system, an anomaly occurring in up to 2% of the population. In this article we present a technique for robot-assisted ipsilateral ureteroureterostomy for treatment of iatrogenic injury of a lower pole moiety ureter in a complete duplex system.

Inguinal lymph node dissection for penile cancer: a contemporary review.

Penile cancer is an uncommon disease associated with significant psychological and physical morbidity. Penile cancer has an expectable pattern of spread in a stepwise fashion, from inguinal to pelvic lymph nodes (PLN) then distant spread. Patients with penile cancer have variable survival, with patients with a low burden of nodal metastatic disease having lasting survival with surgical management, however patients with a large amount of locoregional metastatic disease having a worse prognosis. The current management options for patients with metastatic lymph node disease in penile cancer aims to reduce the morbidity associated with radical inguinal lymph node (ILN) surgery with appropriate risk stratification to optimise oncological control of the disease. This article describes current challenges in managing the inguinal region in patients with penile squamous cell carcinoma (SCC).

Indirect Comparisons of Efficacy between Combination Approaches in Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Network Meta-analysis.

CONTEXT: There have been substantial changes in the management of men with metastatic hormone-sensitive prostate cancer (mHSPC) over the past 5 yr, with upfront combination therapies replacing androgen-deprivation therapy (ADT) alone. A range of therapies have entered the space with no clear answer regarding their comparative efficacy. OBJECTIVE: To perform a systematic review and network meta-analysis to characterise the comparative efficacy of combination approaches in men with mHSPC. EVIDENCE ACQUISITION: We searched multiple databases and abstracts of major meetings up to June 2019 for randomised trials of patients receiving first-line therapy for metastatic disease, a combination of ADT and one (or more) of taxane-based chemotherapy, and androgen receptor-targeted therapies. The primary endpoint was overall survival (OS) and we evaluated progression-free survival as a secondary outcome. We performed subgroup analysis based on the volume of disease. EVIDENCE SYNTHESIS: We found seven trials that met our eligibility criteria using either docetaxel, abiraterone acetate, enzalutamide, or apalutamide in combination with ADT. All agents in combination with ADT were shown to be superior to ADT alone; enzalutamide + ADT had the lowest absolute hazard ratio compared with ADT only (hazards ratio 0.53, 95% confidence interval 0.37-0.75), and an estimated 76.9% probability that it is the preferred treatment to prolong OS compared with other combination treatments, or with ADT alone. Enzalutamide appeared to have better OS compared with docetaxel in men with low-volume disease, but there was no difference in other comparisons. CONCLUSIONS: Combination therapy with any of docetaxel, abiraterone acetate, enzalutamide, or apalutamide provides a significant OS benefit when compared with ADT alone. We did not identify significant differences in OS between different combination therapies. Subtle differences between these options provide clinicians considerable flexibility when selecting options for individual patients. PATIENT SUMMARY: Many men with metastatic, hormone-sensitive prostate cancer should be managed with upfront combination therapy instead of androgen-deprivation therapy alone. Clinicians may consider many factors during the decision-making process, and thus management should be tailored for patients individually.

Characterizing high-grade serous papillary carcinoma of tunica vaginalis.

Serous carcinomas of the testis or para-testis are extremely rare tumors of Mullerian type. We report a case of high-grade serous papillary carcinoma of the tunica vaginalis, treated with radical orchiectomy and hemi-scrotectomy after being referred for a rapidly growing painless scrotal mass. In addition to negative testicular tumor markers, scrotal ultrasound, and conventional computerized tomography (CT) scanning, this patient's workup included a positron emission tomography (PET) scan using F-18-fluoro-deoxyglucose (FDG), demonstrating metabolically avid uptake of the disease. This patient is completing ongoing close follow up and is currently disease free at nine months post definitive treatment.

Robotic prostatectomy following previous major abdominal surgeries resulting from gunshot injury.

Major previous abdominal surgery involving more than one abdominal quadrant may be considered a relative contraindication to robotic assisted radical prostatectomy (RARP) due to the potential increased risk of adhesions, bowel injuries, and is often associated with longer operating time and increased blood loss. We describe the use of a mini-laparotomy to allow safe port placement with extensive open and robotic adhesiolysis at the time of RARP with an excellent post-operative recovery, good oncologic and functional outcomes.

A blind spot in urology: Prostate cancer associated retinopathy.

Paraneoplastic syndromes associated with prostate cancer that cause visual disturbances are rare. We present the case of a 71 year old man with a history of adenocarcinoma of the prostate who developed cancer associated retinopathy concomitant with small cell transformation. This represents an unusual paraneoplastic syndrome that may be progressive and irreversible, requiring prompt diagnosis and treatment to preserve visual function and guide further oncological care.

Erectile dysfunction: a global review of intracavernosal injectables.

PURPOSE: Data assessing the effectiveness of intracavernosal injections (ICIs) for the treatment of erectile dysfunction (ED) are limited. This study evaluates intracavernosal injectable therapies for ED and reviews available guidelines that inform clinical practice. METHODS: A systematic search using electronic databases (Medline, Pubmed) was performed for studies investigating injectable management strategies for ED published after 1990. Primary outcome measures were to comparatively evaluate clinical efficacy, continuation rates and adverse event profiles of each injectable agent as monotherapy or in combination. The secondary outcome measurement was to discuss available guidelines that inform clinical practice for injectable agents. RESULTS: ICIs demonstrate clinical efficacy in 54-100% of patients, early discontinuation rates of ≤ 38% and adverse events in ≤ 26%. Discontinuation rates are typically greatest within 3-6 months of commencement. Anxiety related to the initial injection occurs in approximately 65% and anxiety levels can remain high for 4 months. Approval of intracavernosal injection agents is mainly limited to alprostadil with the recent addition of aviptadil/phentolamine combination therapy in a select few geographical regions. Although combination therapies are attractive alternative options, their formulations are variable and should be standardised before widespread acceptance is achieved. CONCLUSIONS: ICIs are associated with good clinical efficacy rates, high discontinuation rates and a moderate side-effect profile. They represent an important tool in the urological armamentarium for treating ED in patients that cannot tolerate or are refractory to oral therapies.