Welcome to another installment of Uranimals, our video series featuring urologists and their pets. From a dog duo to a group of animals living mountainside, check out our latest guests!

Uranimals: Episode 3

, discusses the background, findings, and takeaways of the VISION trial, which was presented recently at the 2021 Society of Urological Oncology Annual Meeting. Morris is the section head of prostate cancer in the GU oncology service at the Memorial Sloan Kettering Cancer Center in New York, New York.

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"The results of this trial impacted practice globally,” says Michael J. Morris, MD.

Lutetium 177 PSMA enhances QOL in patients with mCRPC

, discusses the background and findings of the study, “Impact of 18F-Fluciclovine PET/CT on plans for ADT in patients with biochemical recurrence of prostate cancer; data analysis from two prospective clinical trials,” presented recently at the 2021 Society of Urologic Oncology Annual Meeting. Andriole is a Robert Killian Royce distinguished professor of urologic surgery at the Washington University School of Medicine in St. Louis, Missouri.

“For most men, we can identify the specific site or sites of recurrence, and thereby use a more directed therapy that specifically targets the abnormal sites,” says Gerald L. Andriole, MD.

Dr. Andriole discusses promise of 18F-fluciclovine for managing biochemically recurrent prostate cancer

, discusses the background and findings of the study, “The efficacy of enzalutamide (Enza) plus androgen deprivation therapy (ADT) on oligometastatic hormone-sensitive prostate cancer: extended post hoc analysis of ARCHES,” presented recently at the 2021 Society of Urologic Oncology Annual Meeting. Armstrong is a professor of medicine, surgery, and pharmacology and cancer biology at Duke University and a member of the Duke Cancer in Durham, North Carolina.

“The good news for patients is that the survival and radiographic progression-free survival [were] substantially improved in all subsets,” says Andrew J. Armstrong, MD, MSc.

Post hoc analysis investigates enzalutamide plus androgen deprivation therapy in men with oligometastatic prostate cancer

, discusses the key points of the debate, “What is the Preferred Approach for Low Risk Prostate Cancer?” being presented today at the 2021 Society of Urological Oncology Annual Meeting. Eggener is a Bruce and Beth White Family professor of surgery and radiology, vice chair of the section of urology, and director of the High Risk and Advanced Prostate Cancer Clinic at the University of Chicago Medical Center in Chicago, Illinois.

"It’s an important topic to debate,” says Scott E. Eggener, MD.

Dr. Eggener on active surveillance: “There’s superb long-term outcomes”

, discusses the key points of her presentation, “Advanced disease: incorporating molecular markers and genomic studies into therapy,” presented recently at the 2021 Society of Urologic Oncology Annual Meeting. Morgans is a genitourinary medical oncologist and medical director of the Survivorship Program at the Dana-Farber Cancer Institute in Boston, Massachusetts.

“There are so many advances in prostate cancer, many of which are actually targeted,” says Alicia K. Morgans, MD, MPH.

Dr. Morgans on prostate cancer: “There are so many advances”

Adding darolutamide (Nubeqa) to docetaxel and androgen deprivation therapy (ADT) significantly improved overall survival (OS) versus docetaxel and ADT alone in men with metastatic hormone-sensitive prostate cancer (mHSPC), according to findings from the phase 3 ARASENS trial.

Safety with the darolutamide regimen was also reported to be comparable to the control arm. Bayer, the developer of the oral androgen receptor inhibitor, reported in a press release that the data from the study will be presented at an upcoming medical meeting, and that the company plans to discuss the results with regulatory agencies worldwide regarding an indication in this setting.

“For patients with mHSPC, there remains a significant need for new therapeutic approaches that improve treatment outcomes. ARASENS was prospectively designed to investigate whether combining NUBEQA with docetaxel and ADT could lead to an increase in overall survival for men with mHSPC,” Scott Z. Fields, MD, senior vice president and head of Oncology Development at Bayer's Pharmaceutical Division, stated in the press release.

Overall, the phase 3 multicenter, double-blind ARASENS trial randomized 1306 newly diagnosed patients with mHSPC in a 1:1 ratio to docetaxel and standard ADT plus either darolutamide (600 mg twice daily) or matching placebo. OS was the primary end point with secondary end points including time to castration-resistant prostate cancer (CRPC), time to initiation of subsequent anticancer therapy, time to first symptomatic skeletal event, time to pain progression, and safety.

Darolutamide is currently approved for the treatment of patients with nonmetastatic CRPC. The approval was based on data from the double-blind ARAMIS trial, which included 1509 patients with nonmetastatic CRPC. Patients were randomized in a 2:1 ratio to receive oral darolutamide at 600 mg twice daily plus androgen deprivation therapy (ADT; n = 955) or placebo plus ADT (n = 554).

The primary data from the trial showed that in the overall population, the median metastasis-free survival was 40.4 months in the darolutamide cohort and 18.4 months in the placebo cohort, translating to a 59% reduction in the risk of metastases or death (HR, 0.41; 95% CI, 0.34-0.50; 

Subsequent to the FDA approval, the agency updated darolutamide’s label to include OS data from the ARAMIS trial.

 These data showed that adding darolutamide to ADT reduced the risk of death by 31% compared with ADT plus placebo in men with nonmetastatic CRPC (HR, 0.69; 95% CI, 0.53-0.88; 

 At a median follow-up of 29 months, the 3-year OS rates were 83% and 77% in the darolutamide and placebo arms, respectively.

This OS benefit was reached even though over half (55%) of the patients on the control arm received darolutamide (n = 170) or other subsequent treatments (docetaxel, abiraterone acetate [Zytiga], enzalutamide [Xtandi], sipuleucel-T [Provenge], and cabazitaxel [Jevtana]) after the study was unblinded.

Darolutamide is also being evaluated in the ongoing double-blind phase 3 ARANOTE trial (NCT04736199), in which men with mHSPC are being randomized to ADT plus either darolutamide or placebo. The primary end point of the ARANOTE trial is radiological progression-free survival.

1. Phase III Investigational Trial of NUBEQA® (darolutamide) in Combination with Docetaxel and Androgen Deprivation Therapy (ADT) Meets Primary Endpoint of Significantly Increasing Overall Survival (OS) in Patients with mHSPC. Published online December 3, 2021. Accessed December 3, 2021. https://bwnews.pr/3GbjkTl.

2. U.S. FDA Approves Addition of Overall Survival and Other Secondary Endpoint Data to NUBEQA® (darolutamide) Prescribing Information. Posted online January 8, 2021. https://bit.ly/2L60YfW. Accessed January 8, 2021.

3. Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049. doi: 10.1056/NEJMoa2001342.

Articles

Adding darolutamide to docetaxel and androgen deprivation therapy significantly improved overall survival in men with metastatic hormone-sensitive prostate cancer. 

Darolutamide improves overall survival in mHSPC

, discusses key points of a case-based discussion on intermediate-risk non-muscle invasive bladder cancer taking place during the 2021 Society of Urologic Oncology Annual Meeting. Scarpato is an associate professor, residency program director, and vice chair of education in the department of urology at the Vanderbilt University Medical Center in Nashville, Tennessee.

“[I focused on] why this such an important topic and how we might better counsel our patients,” says Kristen Scarpato, MD, MPH.

Dr. Scarpato highlights case-based discussion on intermediate-risk NMIBC

Next-generation sequencing (NGS) via urine cytology specimens may represent a valid, minimally invasive profiling tool for assessing genomic alterations in upper tract urothelial carcinoma (UTUC), according to a poster presented during the 2021 Society of Urologic Oncology Annual Meeting.

Specifically, researchers concluded that the overall success rate of NGS of urine cytology specimens from UTUC was 86% and that the derived genomic profiles were similar to those obtained via ureteroscopic biopsies and radical nephroureterectomies.

“Many times, genomic profiling is from tissue from FFPE cell blocks–obtaining tissue requires invasive surgical procedures, and DNA is often moderately degraded,” explained Wesley Yip, MD, urologic oncology fellow at Memorial Sloan Kettering, in a presentation of the findings. “Our group has previously shown that urine cytology specimens, at least in the context of [patients with] non-muscle invasive bladder cancer treated with BCG, present a potential source for genomic analysis. So, we asked the question: ‘Can genomic profiling upper tract tumors be performed through cytology specimens.’”

Researchers compared a total of 14 urine cytology specimens from UTUC tumors with paired tissue specimens including ureteroscopic biopsies and radical nephroureterectomies. The 20 most frequently altered genes in the urine cytology samples were consistent with the gene alterations present in the tissue samples. In both specimen groups, TERT (in cytology vs tumor specimen, 50% vs 67%, respectively), KMT2D (50% vs 67%), and FGFR3 (42% vs 58%) represented the most prevalent genomic mutations.

The tumor specimen findings yielded a total of 124 gene alterations, with TERT (67%), FGFR3 (58%), KMT2D (67%), and STAG2 (50%) as the most prominent mutations. The average tumor mutation burden was 12.3 (range, 2.6-61.4) in this collection of samples. Other prevalent mutations included CREBBP (33%), CCND1, FLT4, and KMT2C (all 25%), and ELF3, PRKD1, MAPKAP1 (all 20%).

Urine cytology specimen findings identified a total of 66 genomic alterations and the TMB average was 8 (range, 2.6–16.7). The most common alterations identified in this collection included FGFR3 (42%), KMT2D (50%), and TERT (50%). Other prevalent alterations included STAG2 (33%) and PIk3CA (25%).

“We demonstrate an 86% success rate of next generation sequencing of urine cytology specimens from upper track tumors. There are similar genetic profiles between the urine cytology, specimens and tissue specimens are there from biopsy or radical nephroureterectomy,” concluded Kip. “This demonstrates that urine cytology is actually a useful minimally invasive tool but has some room for improvement. Sequencing these specimens has the potential for risk stratification and treatment response monitoring.”

1. Yip W, Reisz P, Tracey A, et al. Feasibility and validation of genomic profiling of upper tract urothelial carcinoma from urine cytology specimens. Presented at: SUO 22nd Annual Meeting; December 1-3, 2021; Orlando, Florida. Poster 120.

Urine cytology specimen NGS was found to be a feasible and valid method of assessing genomic alterations in patients with upper tract urothelial carcinoma.


Urine cytology NGS comparable to tumor biopsy in identifying UTUC mutations

Following an increase of adoption among surgeons, segmental ureterectomy (SU) appeared to be non-inferior to radical nephroureterectomy (RNU) in treating patients with high-risk upper tract urothelial carcinoma (UTUC), according to findings presented at the 2021 Society of Urologic Oncology Annual Meeting.

“Radical nephroureterectomy is widely considered the gold standard for high-risk upper tract urothelial carcinoma. Segmental ureterectomy has had increased adoption for high-risk UTUC, particularly for distal ureteric tumors, but its oncological equivalence remains unclear,” Siv Venkat, MD, FRCS, urology fellow, Weill Cornell Medical College, said in a virtual presentation of the findings. “The purpose of this poster was to examine current trends in RNU and SU for upper tract disease, look at patient factors contributing to the performance of SU, look at the rates of lymph node dissection, and look at survival for RNU and SU in this high-risk disease population.”

The researchers utilized the National Cancer Database to identify 30,861 patients with nonmetastatic UTUC with urothelial histology who underwent extirpative surgery from 2004 to 2016. In total, 26,153 patients (84.7%) underwent RNU and 4,708 (15.3%) underwent SU.

Overall, patients who underwent SU were older; were more likely to have surgery at an academic/research hospital; had lower cT, cN, pT, and pN stages; had pM0 disease; had low grade tumors; had procedures done through open surgery; and had a higher rate of positive margins (

SU for lymph node dissection was more likely, compared with RNU (32.3% vs 23.0%; 

 < .001). “This was consistent across high-grade tumors, tumors over 2 cm, and pT2-3 disease,” Venkat said.

Among those with lymph node dissection, SU induced higher nodal yields (mean, 6.07 nodes), compared with RNU (mean, 5.69 nodes).

Lastly, SU demonstrated improved median overall survival, compared with RNU (66.1 months vs 64.9 months, respectively; 

 = .025). However, Venkat noted, this trend was not consistent across the high-risk subgroups, including high-grade tumors (median OS, 53.1 months vs 52.3 months, respectively; 

 = .14), tumors over 2 cm (58.5 months vs 61.2 months; 

 = .37), pT2 disease (54.0 months vs 60.3 months; 

Venkat and colleagues acknowledged the study was limited by potential selection bias andconfounders because it was a national registry-based study; lack of representation of an international population; detection bias, as patients and clinicians were not blinded; potential coding errors; no central pathology review; unknown templates used for surgical approaches; and potential challenges with clinically staging UTUC.

“Prospective studies are still needed to be done,” Venkat said. “So segmental ureterectomy appears to be non-inferior to radical nephroureterectomy in patients. It does appear that surgeons are having a better level of dissection [with] segmental ureterectomy.”

1. Venkat S, Lewicki P, Basourakos S, Borregales L, Scherr D. Comparison of Radical Nephroureterectomy and Segmental Ureterectomy in Upper Tract Urothelial Carcinoma. Presented at: SUO 22nd Annual Meeting; December 1-3, 2021; Orlando, Florida. Poster 114.

Findings presented at the 2021 Society of Urologic Oncology Annual Meeting demonstrate that segmental ureterectomy may be comparable to radical nephroureterectomy.

Segmental ureterectomy non-inferior to radical nephroureterectomy in high-risk UTUC

Benjamin P. Saylor is associate editor of Urology Times, an Advanstar Communications publication.

Restaging transurethral bladder resection of the tumor (TURBT) prior to radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) is associated with similar rates of pathologic upstaging, investigators reported at the 2021 Society of Urologic Oncology Annual Meeting.

For the study, presented by first author Justin Mehr, BS, of Baylor College of Medicine Dan L Duncan Comprehensive Cancer Center in Houston, Texas, the investigators compared staging accuracy between re-TURBT clinical stage and pathologic stage in patients who underwent a post-NAC re-TURBT prior to RC vs those who underwent a re-TURBT prior to RC but did not receive NAC.

The investigators used a prospectively maintained, internal review board-approved institutional database for the study and identified 129 patients who underwent RC between 2013 and 2019 with a re-TURBT prior to RC. Of these patients, 53 received NAC between their initial and re-TURBT and 76 patients did not receive NAC.

Median patient age at RC was 69.5 years. Most of the patients (107, 82.9%) were men, and 121 (93.8%) were White.

The investigators found that the overall upstaging rate from re-TURBT to RC was 34.9%, with 31.0% upstaged in the NAC group and 37.0% in the no-NAC group (

Looking at patients who showed absence of residual disease (cT0, n = 21), “We found there was no difference in the rate of absence of tumor on pathologic staging, with 38.5% for the NAC group and 37.5% for no-NAC group [

The investigators also looked at re-TURBT with staging less than rT2 as a predictor for absence of muscle-invasive bladder cancer on pathologic staging. They found there was no significant difference between the groups, with negative predictive values of 69.0% and 66.7% for the NAC and no-NAC groups, respectively (

Mehr reported that all patients who were node positive on initial TURBT were pathologic stage T2 or greater following chemotherapy and re-TURBT (n = 7), and that out of patients who were clinical stage T1 at post-NAC TURBT, 62.5% were pT2 or higher.

Mehr also noted, “With a high rate of patients who were clinical stage T1 on post-NAC re-TURBT having muscle-invasive bladder cancer on pathologic staging, these patients will be eligible for adjuvant immunotherapy with nivolumab [Opdivo] and clinical trial testing alternative adjuvant regimens.”

“While we have consistently found that one of the best predictors of positive clinical and survival outcomes is pT0 following RC, challenges remain regarding the accuracy of clinical staging with restaging TURBT and [exam under anesthesia]. Clinical trials that are testing bladder preservation in these patients require careful follow-up to determine outcomes relative to the potential for residual bladder cancer and occult disease,” Mehr said in his concluding remarks.

1. Mehr J, Bates JN, Lerner SP. Benefit of re-staging transurethral resection of bladder tumor prior to radical cystectomy with or without neoadjuvant chemotherapy. Paper presented at: 2021 Society of Urologic Oncology Annual Meeting; December 1-3, Orlando, Florida. Abstract 79. https://suo-abstracts.secure-platform.com/a/gallery/rounds/12/details/1530

The investigators found that the overall upstaging rate from re-TURBT to RC was 34.9%, with 31.0% upstaged in the NAC group and 37.0% in the no-NAC group (P = .584).

Urine cytology NGS comparable to tumor biopsy in identifying UTUC mutations

Segmental ureterectomy non-inferior to radical nephroureterectomy in high-risk UTUC

Re-TURBT prior to cystectomy has similar pathologic upstaging rates regardless of NAC status