AUA 2020

AUA 2020: Identifying the Frequency of Actionable Genomic Alterations in Localized and Metastatic Upper Tract Urothelial Carcinoma

( Upper tract urothelial carcinoma tumors have distinct genomic profiles that distinctly differentiate them from bladder cancer tumors.

In the presented study, the authors characterized the prevalence of actionable genomic alterations and evidence supporting susceptibility to targeted therapies. In addition, they evaluated the prevalence of DNA damage response alterations associated with response to platinum-based chemotherapy and PD-1/PD-L1 blockade.

It has been shown that key differences in the genomic landscape of high-grade upper tract urothelial carcinoma can have the potential to alter treatment paradigms.

For this study, upper tract urothelial carcinoma tumors that underwent next-generation sequencing using the MSK-IMPACT platform were identified from a prospectively maintained institutional database.

Patients were grouped by clinical disease state (localized vs. metastatic) at the time of sequencing.  Actionable cancer gene alterations were identified using the OncoKB platform and classified based on the level of evidence. Additionally, the authors identified 34 genes within the MSK-IMPACT as DDR-related based on Pubmed searches and NCBI gene and biosystems database.

In 2019, Erdafitinib received FDA approval for the treatment of urothelial tumors, which harbored fusions in FGFR2 or FGFR3 and oncogenic mutations in FGFR3.1

Alterations resulting in loss of function in mismatch repair genes can lead to microsatellite instability-high phenotype. Mismatch repair status has been shown to be predictive of clinical benefit from pembrolizumab across all solid tumor carcinomas.2

In this cohort, a total of 206 tumors were sequenced (145 localized, and 61 metastatic). At least one actionable alteration was found in 91% of the cohort (93% of patients with localized disease, and 89% of patients with metastatic disease), as seen in Figure 1.

Figure 1 – Genomic alterations identified in the cohort:

Somatic alterations in genes associated with DNA damage response and repair are associated with enhanced platinum responsiveness, leading to a higher likelihood of pathological downstaging in neoadjuvant treated bladder cancers(3). Data from the authors’ institution also suggest that DDR mutations are associated with improved anti-PD1/PD-L1 responsiveness, possibly through modulation of tumor mutational burden(4).

At least one DDT alteration was found in 39% of the overall UTUC cohort (38% of clinically localized and 40% of metastatic patients), as seen in Figure 2.

Figure 2 – Frequency of alteration in DNA damage repair genes:


The authors concluded that most tumors evaluated in this study harbor actionable genomic alterations in both the localized and the metastatic setting, demonstrating the important role genetic testing may play in the management of UTUC.

These presented findings could hopefully be used to guide rational in planning clinical trial design with targeted therapies.

Presented by: Andrew Tracey, MD, Memorial Sloan Kettering Cancer Center, New York, NY, USA 

Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27-28, 2020.


  1. Loriot Y, Necchi A, Park SH, Garcia-Donas J, Huddart R, Burgess E, et al. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. New England Journal of Medicine. 2019;381(4):338-48.
  2. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. New England Journal of Medicine. 2015;372(26):2509-20.
  3. Teo MY, Bambury RM, Zabor EC, Jordan E, Al-Ahmadie H, Boyd ME, et al. DNA Damage Response and Repair Gene Alterations Are Associated with Improved Survival in Patients with Platinum-Treated Advanced Urothelial Carcinoma. Clinical Cancer Research. 2017;23(14):3610-8.
  4. Teo MY, Seier K, Ostrovnaya I, Regazzi AM, Kania BE, Moran MM, et al. Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers. Journal of Clinical Oncology. 2018;36(17):1685-94.

AUA 2020: Pembrolizumab Plus Enzalutamide in Abiraterone-Pretreated Patients With Metastatic Castration-Resistant Prostate Cancer: Updated Results From KEYNOTE-365 Cohort C

( Patients who were treated with enzalutamide have shown increased expression of PD-L1 in circulating dendritic cells. Patients with greater PD-L1 expression were found to have worse response rates to enzalutamide treatment.1

There is a phase 2 single-institution study that assessed pembrolizumab + enzalutamide in patients whose disease progressed after enzalutamide (n=28)(2). In these patients, the radiographic response rate was 25%. Furthermore, 18% had a greater than 50% decline in PSA from baseline and a median overall survival of 22.2 months(2).

Initial data from the cohort C of KEYNOTE-365 showed that pembrolizumab + enzalutamide are generally well-tolerated and showed promising activity in patients with metastatic castrate-resistant prostate cancer, previously treated with abiraterone.

In this presentation, the authors present updated data from the KEYNOTE-365 cohort C after additional enrollment, extended follow-up, and with more radiologic data.

The study design of KEYNOTE 365 cohort C is shown in Figure 1, the patient disposition is shown in figure 2, and the baseline characteristics are shown in Figure 3.

Figure 1 – KEYNOTE 365 - COHORT C:


Figure 2 – Patient disposition:


Figure 3 – Baseline characteristics:


Figure 4 demonstrates the confirmed PSA response rate and the percentage change from baseline. Figure 5 depicts the time to PSA progression. A total of 56% of patients experienced a reduction in target lesions, and 24% experienced a reduction greater than 30%. Figure 6 shows the radiographic progression free-survival and overall survival.

Figure 4 – PSA response rate and percent change from baseline:


Figure 5 – Time to PSA progression:


Figure 6 – Radiographic progression-free survival and overall survival:


The treatment-related adverse effects showed that 90.2% of patients experienced any kind of adverse effect, while 21.6% experienced grade 3-5 adverse effects.

The authors concluded that this data that had incorporated increased enrollment and additional follow up showed that pembrolizumab and enzalutamide continue to show promising activity in patients with metastatic castrate-resistant prostate cancer, who were previously treated with abiraterone. This promising activity manifested in:

  • Confirm the PSA response rate for the total population of 21.8%
  • objective response rate per RECIST v1.1 in patients with measurable disease of 12%
  • Disease Control rate with a total population of 34.8%
  • radiographic progression-free survival of 6.1 months with overall survival of 20.4 months
  • The safety and tolerability profile of pembrolizumab and enzalutamide was consistent with that of previously published data. There was an increased incidence of all grade rash (19.6%) and grade 3 rash (7.8%), which resolved with the standard of care treatment.

The promising results of this study support further evaluation of pembrolizumab and enzalutamide in patients with metastatic castrate-resistant prostate cancer who were previously treated with abiraterone.

There is currently an ongoing randomized phase 3 study of enzalutamide with or without pembrolizumab, that is open to enrollment (KEYNOTE-641, NCT03834493) for patients with metastatic cancer-resistant prostate cancer who did not receive chemotherapy, and who are intolerant to or progressed on or after abiraterone acetate therapy.

Presented by: Evan Yu, MD, Professor, University of Washington, Seattle, WA, USA 

Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020.


  1. Bishop JL, Sio A, Angeles A, Roberts ME, Azad AA, Chi KN, et al. PD-L1 is highly expressed in Enzalutamide resistant prostate cancer. Oncotarget. 2015;6(1):234-42.
  2. Graff JN, Alumkal JJ, Thompson RF, Moran A, Thomas GV, Wood MA, et al. Pembrolizumab (Pembro) plus enzalutamide (Enz) in metastatic castration resistant prostate cancer (mCRPC): Extended follow up. Journal of Clinical Oncology. 2018;36(15_suppl):5047-.
Related Content: 
Read: Keynote-365 cohort a: Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).
Read: ASCO GU 2020: KEYNOTE-365 Cohort A Updated Results: Pembrolizumab Plus Olaparib in Docetaxel-Pretreated Patients with mCRPC

AUA 2020: Comparison of Prostate-Specific Membrane Antigen-Targeted Radionuclide Therapy with Lutetium-177 via Antibody J591 vs. Small Molecule Ligand PSMA-617

( Prostate-specific membrane antigen (PSMA) is selectively overexpressed in most advanced prostate cancer tumors with limited expression in other organs (including celery and lacrimal glands, renal tubules, and small intestines).

Sequential prospective clinical trials of anti-PSMA mAb J591 and small molecule PSMA-617 radiolabelled with the beta emitter 177 LU, demonstrated tolerability with accurate targeting in an unselected patient population with metastatic castrate-resistant prostate cancer. It also has shown a dose-response relationship with prostate-specific antigen (PSA) and overall survival.

Figure 1 demonstrates the differences between the mAb and Ligand, and Figure 2 demonstrates the differences between antibody, minibody, and small molecule.

Figure 1 – Differences between mAb and Ligand:


Figure 2 – Differences between antibody, minibody, and small molecule:


The authors hypothesized that because of the difference in physical properties that lead to differences in kinetics and biodistribution, the adverse events observed following LU-J591 and Lu-PSMA-617 will most likely be different.

In the presented study, the authors extracted all adverse effects data, PSA changes, and overall survival information from the prospective clinical trial data, which enrolled patients with metastatic castrate-resistant prostate cancer, who were treated with PSMA-targeted lutetium-177.

The primary endpoint was the comparison of selected treatment-emergent adverse events between J591 and Lu-PSMA-617. Exploratory endpoints included PSA decline and overall survival. Baseline characteristics are shown in Table 1.

Table 1- Baseline characteristics:


The results demonstrated in Table 2 show that there were more hematological treatment-emergent adverse events with mAb targeting, while there were more none-hematological treatment-emergent adverse events with ligand treatment, even after controlling for dose.

Table 2 – Comparison of adverse events:


The results also demonstrated there was more than 30% PSA decline with PSMA-617 (adjusted OR 6.37, 95% CI 2.97-14.46), compared to J591.

Additionally, the unadjusted median overall survival with PSMA-617 was shorter than for J591 (14.2 vs. 19.6 months). On multivariable analysis, significant associations with overall survival were seen with:

  • A higher administered dose
  • CALGB (Halabi) prognostic group
  • Subsequent receipt of FDA-approved life-prolonging therapies (docetaxel, sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, radium-223)

The limitations of this study include the fact that there was a lot of variability in the patients enrolled, as they were enrolled between 2002 and 2019, with many changes occurring along the way. Additionally, several of the trials were dose-escalation studies, affecting the dose patients received. Lastly, a different version of the adverse events grading system was used through the years (CTCAE v3 used in early studies vs. CTCAE v4 used in later studies).

The authors concluded that as they had originally hypothesized:

  • PSMA targeted 177Lu delivered via intact antibody J591 is associated with more hematologic toxicity than with small molecule delivery
  • PSMA targeted 177Lu delivered via small molecule PSMA-617 is associated with more non-hematological toxicity than antibody delivery
  • 177Lu-PSMA-617 was shown to be associated with more PSA decline than Lu-J591, but no difference in overall survival was evident on multivariable analysis
Presented by: Scott Tagawa, MD, MS, FACP, Weill Cornell Medicine, New York, NY, USA

Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27-28, 2020.

Related Content: 
Read: Preparing Your Practice for the New Era of Theranostics

AUA 2020: Effect of Cabazitaxel vs. Abiraterone or Enzalutamide on Patient-Reported Outcomes in Metastatic Castration-Resistant Prostate Cancer: A Pre-Planned EQ-5D-5L Analysis of the CARD Study

( The CARD study (Figure 1) was a multicenter, randomized, open-label study enrolling patients with metastatic castrate-resistant prostate cancer who progressed in less than 12 months on prior androgen receptor-targeted agent1 (before or after docetaxel therapy).

AUA 2020: Abiraterone is Associated with Higher Odds of Cardiac Complications Compared to Enzalutamide

( Androgen deprivation therapy (ADT) is the mainstay of treatment for advanced prostate cancer. In recent years there has been a rapid increase in therapeutic options for advanced cancers. Many drugs have been approved for the same setting (docetaxel, enzalutamide, abiraterone, darolutamide, apalutamide, and olaparib). Despite the plethora of drugs that have been approved, there has been minimal head to head data assessing clinical efficacy and toxicity profile.

It is known that any hormonal deprivation induces a hypogonadal state with many side effects, including cardiac risk. Cardiac disease is the leading non-cancer cause of death in men with prostate cancer. There are some data suggesting the GnRH agonists and antagonists may have different cardiac risk profiles.1

It currently remains unclear whether abiraterone or enzalutamide confer a similar cardiac risk.

Pharmacovigilance is the collection, detection, assessment, and monitoring of adverse events related to pharmaceutical products.

Vigibase is a World Health Organization's (WHO) global Individual Case Safety Report database that contains individual case safety reports (ICSRs) submitted by the participating member states enrolled under WHO's international drug monitoring program. It is the single largest drug safety data repository in the world. In 2007 it had 3.8 million individual case safety reports, and in 2014 it increased to 10 million, with over 150,000 drug products monitored in 136 countries.

In the presented study, the authors examined the rates of cardiac events for both enzalutamide and abiraterone (including myocardial infarction, heart failure, carditis, valvular dysfunction, arrhythmias, and others). Table 1 demonstrates the number of patients with the various cardiac events that were analyzed.

Table 1 – Patients with cardiac events:


The authors report 2433 cardiac adverse events that were identified with most reported outside a trial (77%). Most patients were older than 65 (66%), and the most frequent events were myocardial infarction and heart failure, which were also the most fatal. The cumulative incidence of time to adverse drug reaction from initiation to treatment can be shown in Figure 1.

Figure 1 –


The summarized results demonstrating the association of the various drugs to cardiovascular events are shown in Figure 2.

Figure 2 – Association of the various drugs to cardiovascular events:


These results show an increased cardiac risk with abiraterone and GnRH agonists, which is in line with previous data. In contrast, enzalutamide had no disproportional association with any cardiac adverse events.

This interesting study has several limitations, including the fact that Vigibase reports data from various different sources, resulting in the probability that an adverse event is drug-related not being similar in all cases. Furthermore, medication sequencing may play an undetected role, and that not all adverse events are capture by Vigibase.

Despite these limitations, the authors concluded that there is an increased risk for cardiac events in patients using GnRH agonists and abiraterone, but not enzalutamide.

Presented by: Eugene Cone, MD, Brigham and Women's Hospital, Newton, MA, USA 

Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020.


  1. Albertsen PC, Klotz L, Tombal B, Grady J, Olesen TK, Nilsson J. Cardiovascular morbidity associated with gonadotropin-releasing hormone agonists and an antagonist. Eur Urol. 2014;65(3):565-73.

AUA 2020: Inherited Cancer Predisposition Gene Variants in Patients with Non-Muscle Invasive Bladder Cancer

( The genetic landscape of bladder cancer has been generally poorly examined, compared for example with prostate cancer. However, there are intriguing emerging data that suggest that many patients with locally advanced and metastatic urothelial cancer harbor rare germline variants in cancer predisposition genes, including in DNA damage response (DDR) genes. This, however, has not been thoroughly studied in patients with non-muscle invasive bladder cancer (NMIBC), who represent the vast majority of patients newly diagnosed with bladder cancer. In a podium presentation at the American Urological Association (AUA) 2020 Virtual Meeting, Dr. Pietzak and colleagues presented results of a prospectively accrued cohort of patients with non-muscle invasive bladder cancer who were examined for germline variant in cancer predisposition genes.

AUA 2020: The Role of the Urinary, Fecal, and Prostatic Microbiome in Prostate Cancer: A Systematic Review

( More data is being published regarding the growing role of the microbiome in the pathogenesis and treatment of cancers in general, and prostate cancer specifically. However, there is still a lack of conclusive evidence regarding its association and impact on prostate cancer disease and treatment.

AUA 2020: Pivotal Trial of MRI-Guided Transurethral Ultrasound Ablation in Men with Localized Prostate Cancer: Two-Year Follow-Up

( Prostate cancer is the most common non-cutaneous malignancy among men in the western world, with the vast majority of men having clinically localized disease at the time of diagnosis. For patients with low-risk disease, active surveillance is widely accepted. For patients opting for active treatment, currently accepted treatments including radical prostatectomy and radiotherapy provide good cancer control as evidenced by very high 5-year cancer-specific survival. However, each is associated with significant toxicity. Thus, there has been much ongoing work to identify treatments that provide cancer control with a lower toxicity profile. One such approach is prostate ablation. MRI-guided transurethral ultrasound ablation (TULSA) is a novel minimally-invasive procedure for prostate ablation. In a podium presentation at the American Urologic Association Virtual Annual Meeting, Dr. Eggener and colleagues presented the two-year results of the multicenter TULSA-PRO Ablation Clinical Trial (TACT).

AUA 2020: Decision-Analytic Modeling Study of the PRECISION Trial: Does Pre-Biopsy MRI Do More Good Than Harm?

( The utilization of multiparametric magnetic resonance imaging (mpMRI) in the diagnosis and management of prostate cancer has rapidly expanded in the past few years. The recent PRECISION trial, along with others, have examined the value of mpMRI prior to prostate biopsy in men with elevated PSA levels. In general, these studies have demonstrated a decrease in the detection of low-grade prostate cancer along with concomitant increase in the diagnosis of high-grade prostate cancer for men undergoing MRI prior to biopsy. This has been interpreted widely as supporting the role of MRI.

AUA 2020: Impact of Baseline Disease Volume and Prior Docetaxel Therapy On Prostate-Specific Antigen-Related Outcomes in Patients With Metastatic Hormone-Sensitive Prostate Cancer Treated with Enzalutamide plus Androgen Deprivation Therapy

( Enzalutamide is an approved drug in the United States for the treatment of metastatic hormone-sensitive prostate cancer based on the phase three ARCHES study (NCT02677896)1 and supported by the phase 3 ENZAMET trial (NCT02446405).2 Both these trials demonstrated improved clinical outcomes, including radiographic progression-free survival and overall survival with enzalutamide versus the comparator arm. 

AUA 2020: Surrogate Endpoints for Overall Survival for Patients with Metastatic Hormone-Sensitive Prostate Cancer in the CHAARTED Trial

( Prostate cancer is the most commonly diagnosed male malignancy, developing in one out of nine men during their lifetime. Metastasis free survival has been shown to be a robust surrogate for overall survival in men with non-metastatic prostate cancer. However, this surrogate only holds true for a select subset of patients and leaves those trials analyzing metastatic disease at a disadvantage.

AUA 2020: Prostate Mapping for Cancer Diagnosis: The Madrid Protocol — Transperineal Prostate Biopsies Combining Micro-Ultrasound and mpMRI Fusion Biopsy

( There has been rapid uptake in the use of multi-parametric magnetic resonance imaging (mpMRI) in the evaluation and diagnosis of patients at risk for prostate cancer. It is widely felt to be a useful tool that decreases rates of diagnosis of low-risk disease while increasing rates of diagnosis of clinically significant disease. However, it is not without downside including significant cost and the lack of real-time guidance of biopsy requiring fusion systems. In contrast, Micro-Ultrasound (Micro-US) is a high-resolution imaging approach, allowing real-time targeted biopsies. In a podium presentation at the American Urologic Association 2020 Virtual Annual Meeting, Dr. Moises Elias Rodriguez Socarras and colleagues present their work assessing transperineal prostate biopsy accuracy for prostate cancer detection combining Micro-US and mpMRI fusion biopsy during the same procedure.

The authors evaluated 200 consecutive patients who underwent transperineal prostate biopsies combining real-time targeted Micro-US (ExactVuTM) biopsies and mpMRI fusion biopsy in the same procedure between February 2018 and September 2019. Biopsies were performed using the PRIMUSTM Scale and a 3D printed TP guide attached to the 29MHz High-resolution Micro-US transducer.

The authors assessed demographic and clinicopathologic parameters including age, PSA, prostate volume, MRI lesions, prostate cancer diagnosis, clinically significant prostate cancer diagnosis (ISUP > 1), Gleason Group Grade (GG) and complications according to Clavien Dindo. Analysis was performed using McNeamar test and a Logistic Regression Model with p ≤ 0.05 was considered statistically significant.

Among 200 included patients, the median age was 63 years (IQR 58-69).

Prostate cancer was detected in 115 patients (57.5%) with clinically significant disease in 79 (39.5%). Micro-US and MRI together detected significantly more prostate cancer and clinically significant prostate cancer than systematic biopsy alone (p<0.001). No statistically significant difference was detected when comparing mpMRI biopsies vs targeted micro-US (p=0.24). However, 12 additional cases of prostate cancer were diagnosed on the basis of micro-US findings that were missed based on mpMRI-guided and systemic biopsy. Of these, 11 were clinically significant disease.

Both PI-RADS and PRI-MUS are strong predictors of csPCa in Logistic Regression Model (AUC for model with leave-one-out validation = 0.7).


Specifically, for PSA >4, PIRADS>3 there is an improvement in detection rate between PRI-MUS 4 and PRI-MUS 5 (36% GG>1 to 60% GG>1).

The authors conclude that, for men undergoing transperineal prostate biopsy, the use of combined Micro-ultrasound and mpMRI fusion biopsy increases yield of clinically significant prostate cancer.

Presented by: Moises Elias Rodriguez Socarras, Department of Urology, IRCCS San Raffaele Hospital, Ville Turro Division, Milan, Italy

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, Twitter: @WallisCJD, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020.

AUA 2020: Cost-Effectiveness of Maintenance BCG for Intermediate and High Risk Non-Muscle Invasive Bladder Cancer

( Most patients newly diagnosed with bladder cancer have non-muscle invasive disease (NMIBC). For patients with intermediate or high-risk NMIBC and those with carcinoma in situ (CIS), adjuvant treatment with BCG is guideline-recommended on the basis of proven benefits in disease recurrence. BCG is administered with both induction and maintenance phases.

AUA 2020: Is Radiotherapy the Devil’s Work?

( In a plenary session at the American Urologic Association Virtual Annual Meeting, Kenneth Angermeier, MD, FACS moderated a session titled: “Is Radiotherapy the Devil’s Work?” Along with panelists Tamsin Greenwell, MD, Sean Elliott, MD, MS, and Francisco Martins, MD, Dr. Angermeier walked through a discussion of this premise.

To begin, Dr. Angermeier highlighted that radiotherapy is an integral part of treatment for many pelvic cancers including prostate cancer, anorectal cancers, and many gynecologic cancers. Together, these are very common conditions with an estimated 250,000 new prostate, cervical and rectal cancer cases in 2020. Highlighting data on prostate cancer, he highlighted that radiotherapy is commonly utilized with predominately external beam approaches used in recent years, with a decline in the utilization of brachytherapy.


As cancer treatment has improved survival rates, survivorship is an increasingly large issue with increasing opportunities for late radiotherapy toxicity. The toxicity of radiotherapy exhibits significant variability between patients. However, when present, it is both irreversible and may be progressive in nature.


While relatively uncommon, serious complications are often in the purview of urologists and may be potentially devastating, including severe radiation cystitis, rectourethral fistula, prostatopubic or vesicopubic fistula, posterior urethral stenosis, rectovaginal or vesicovaginal fistula, and ureteral obstruction.

Dr. Greenwell then discussed radiation cystitis and overall effect on bladder function. Radiation cystitis, as most urologists know, is relatively common representing 1.4% of elective and 7.2% of emergent urologic admissions. Surgical interventions are required in the majority of patients, with urinary diversion an uncommon but potentially devastating outcome.


Severe hematuria/hemorrhagic cystitis is common among patients treated with pelvic radiotherapy: grade 3 in 5-13% of patients and grade 4 in almost 9%.

Beyond hematuria, radiotherapy may have other long-term effects on the bladder. Based on urodynamic testing, radiotherapy is associated with significantly reduced bladder compliance, reduced maximal cystometic capacity, and increased stress urinary incontinence.


Treatment of these patients can be difficult. However, Dr. Greenwell highlighted the role of botulinum toxin A in ameliorating these urodynamic changes.

Radiotherapy may also affect the upper tract with significant obstruction requiring major reconstructive surgery. While feasible, these surgeries are associated with a substantial need for revision surgery and complication rates.


Dr. Martins then discussed the effect of radiotherapy for gynecologic cancer with a focus on vesicovaginal and rectovaginal fistulae. He began with a case presentation highlighting the potential multi-organ effects of pelvic radiotherapy. In the presented cases, as patient treated with radiotherapy for cervical cancer required gynecologic extirpation for cancer control including hysterectomy, oophorectomy, and pelvic lymphadenectomy. Subsequent development of a vesicovaginal and rectovaginal fistulae required diverting colostomy and bilateral nephrostomy for urinary diversion. A difficult surgical reconstruction was undertaken requiring fistulectomy, partial cystectomy, partial vaginectomy, segmental sigmoidectomy with primary anastomosis, neovaginoplasty, and augmentation cystoplasty. Such a large undertaking is associated with significant recovery period necessitating 7 months prior to colostomy closure.

In the setting of gynecologic cancers, he stressed the tension between “delight and disaster” with common urinary adverse events (67%) and bowel adverse events (80%). Approximately a quarter of all gynecologic cancer patients have high-grade complications within 90 days of treatment. The effects of so-called pelvic radiation disease have a significant effect on quality of life.


Severe complications (grade 3 or greater) occur in more than a quarter of patients receiving radiotherapy for gynecologic cancers. Urinary diversion is indicated for radiation cystitis, and also for irreparable vesicovaginal fistula.

Finally, Dr. Elliott discussed anterior prostatopubic or vesicopubic fistulae. These are rare clinical entities and are most often associated with radiotherapy with or without TURP (90%). The majority of these patients are treated with cystectomy while a small minority are candidates for reconstruction.

Identification of these patients is often difficult due to a variety of symptoms for pubic osteomyelitis.


Dr. Elliott highlighted that pelvic MRI is critical to the diagnosis. T1 sequences are helpful to identify osteomyelitis while T2 sequences are important in visualizing the urinary findings and the fistula.

For patients with a cavitation defect, significant stricture, or poor bladder function, cystoprostatectomy with urinary diversion is indicated. Dr. Elliott further advocated for 6-12 weeks of intravenous antimicrobial therapy guided based on intra-operative bone culture.


Concordance between bone and urinary cultures is reasonable, but not perfect (63%).

In ideal candidates, reconstructive approaches may be considered such as primary repair or buccal grafts or rectus abdominus flaps.

Presented by: Kenneth Angermeier, MD, FACS, Cleveland Clinic, Cleveland, OH, USA; Tamsin Greenwell, MD, University College London Hospital, London, England; Sean Elliott, MD, MS, University of Minnesota, Minneapolis, MN; Francisco Martins, MD, University of Lisbon School of Medicine, Santa Maria University Hospital, Lisbon, Portugal

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, Twitter: @WallisCJD, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020.

AUA 2020: John Duckett Memorial Lecture: Effects of Cancer Treatment in Children into Adulthood

( In a plenary session at the American Urologic Association Virtual Annual Meeting this afternoon, Daniel Green, MD, presented the John Duckett Memorial Lecture examining the effects of cancer treatment in children into adulthood.

AUA 2020: Benchmarking Current Nephrectomy Practice in Malignant Disease in England: An Analysis of the BAUS Complex Operation Registry

( Public reporting of surgical outcomes is controversial in North America but widely mandated in England as the basis of the ‘Consultant Outcomes Publication’. In this publication, urologists in England performing nephrectomy for cancer are mandated in providing public-facing outcome data. The BAUS complex operations registry is a nationally held repository, providing contemporary benchmarking data to both patients and professionals. In a podium presentation at the American Urologic Association Virtual Annual Meeting, Dr. John Pascoe and colleagues present a retrospective review of patients undergoing nephrectomy for cancer.

AUA 2020: Expanding Kidney-Sparing Options for Patients with Low-Grade Upper Tract Urothelial Cancer

( In a sponsored educational session at the American Urologic Association Virtual Annual Meeting, Karim Chamie, MD, presented on the recently expanded kidney-sparing options for patients with low-grade upper tract urothelial cancer.

To begin, Dr. Chamie highlighted the evolution in thinking regarding kidney sparing treatment for patients with upper tract urothelial cancer (UTUC). While kidney-sparing approaches were initially only considered in patients with imperative indications, the usage of this approach has broadened over time.


The rationale for kidney sparing approaches in UTUC comes from a balance of the oncologic outcomes of such extirpative surgery and the consequences of such major surgery. In addition to the immediate peri-operative risks, radical nephroureterectomy is associated with renal insufficiency. This has implications both widely and in the ongoing management of UTUC as it may preclude systemic therapy options and may raise further issues in the case of metachronous development of contralateral UTUC.

Prior observational data have suggested that, among carefully selected patients, kidney-sparing approaches provide similar outcomes to nephroureterectomy, both in terms of overall survival and cancer-specific survival.


Despite these promising data, there are notable limitations to kidney sparing approaches to date. The treatment has primarily been performed with ureteroscopic laser ablation. This approach is associated with high rates of local recurrence requiring re-treatment, in addition to bladder recurrences. In addition, due to technical limitations, some tumors are unable to be treated ureteroscopically.


As we know from extensive experience in urothelial bladder cancer, these tumors are sensitive to topical chemotherapeutic agents. Increasing dwell time has been shown to decrease recurrence rates. However, use in the upper tract has been limited due to dwell time as a result of the natural drainage of the upper tract.


To address this issue, MitoGel or JELMYTO was developed. JELMYTO is a combination of mitomycin C which has a long history of use in urothelial bladder cancer and a reverse-thermal gel which increases dwell time.

Data from the pivotal OLYMPUS trial demonstrated both the feasibility and promising outcomes of such a treatment approach, allowing many patients to avoid extirpative surgery.


To briefly summarize, the authors enrolled patients with new or recurrent non-invasive, low-grade UTUC and treated them with six one weekly JELMYTO instillations. Patients were then evaluated at 3 months following screening for the primary endpoint of complete response. Responders underwent ongoing maintenance therapy.

Nearly 60% of patients in the intention to treat population exhibited complete responses at 3 months.


Among those who had a complete response, 12-month durability rates were high (84.2% by Kaplan Meier analysis).

Dr. Chamie highlighted a number of important adverse reactions associated with JELMYTO treatment including ureteric obstruction. This was reported in 58% of the safety population, with a spectrum of severity.


Dr. Chamie closed by considering some practice considerations in the use of JELMYTO including anesthetic considerations, catheter use, as well as pharmacokinetic properties including excretion and exposure.


Presented by: Karim Chamie, MD, Associate Professor of Urology, University of California, Los Angeles, Los Angeles, CA, USA 

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, Nashville, TN, USA, Twitter: @WallisCJD, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020.

AUA 2020: Interim Analysis of Phase 2 Randomized Prospective Study on Neoadjuvant Apalutamide/Abiraterone Acetate with Prednisone and the Feasibility of Performing Nerve-Sparing Radical Prostatectomy in Men with High-Risk Prostate Cancer 

( Neoadjuvant systemic therapy is a widely established treatment paradigm for many malignancies. However, the use of androgen deprivation therapy is not widely endorsed in patients with non-castrate-resistant prostate cancer. The use of neoadjuvant hormonal therapy has been shown previously to improve pathological outcomes reducing positive surgical margins and increase the incidence of organ-confined disease. However, no survival benefit was ever shown with the use of neoadjuvant hormonal therapy.

It is known that men with high-risk prostate cancer have a 50% risk of enduring biochemical recurrence with surgical treatment alone within 10 to 15 years. Neoadjuvant hormonal therapy can reduce the tumor burden, enabling the performance of a nerve-sparing approach in men with high-risk disease, and increasing their quality of life after surgery.

The newer generation of anti-androgens is more effective at causing castration. This might improve oncological outcomes that were not seen in earlier studies using older generation anti-androgens.

There has been no head to head comparison of neoadjuvant treatment, using the latest generation of anti-androgen medications, followed by radical prostatectomy to immediate radical prostatectomy.

The currently presented study was a randomized phase 3 prospective three-arm trial with a planned postoperative follow up of two years. The primary objective was to evaluate the effect of neoadjuvant androgen deprivation treatments on the feasibility of performing a nerve-sparing radical prostatectomy in patients with high-risk prostate cancer (study design is shown in Figure 1).

Figure 1 – Study design:


The primary outcome was post-surgical potency rate at 12 months, defined as being able to penetrate and complete sexual intercourse satisfactorily in more than 50% of the attempts. Each of the experimental arms of this trial would be compared to the surgery the only arm.

Secondary outcomes included change in tumor volume on pelvic MRI after neoadjuvant therapy which were correlated with clinical outcomes before and after treatment with the androgen receptor antagonist (ARN-509, apalutamide for 3 months) or the combination of androgen receptor antagonist (ARN-509, apalutamide for 3 months) + GNRH agonist + prednisone + abiraterone. Other secondary outcomes included biochemical recurrence rate, pathological T0, positive surgical margins rate, postoperative continence rate (being pad free), and quality of life assessed by the EPIC questionnaire.

A total of 32 patients were enrolled since November 2019, with 24 patients remaining in the follow-up phase. There was no significant difference in the operative time between the three arms. The median reduction of tumor volume was 32.4% and 55.7% in arm 1 and arm 2, respectively. Positive surgical margins were noted in 3,1 and 3 patients in arms 1,2, and 3, respectively. Potency was achieved by 50%, 14.2%, and 28.5% of the patients in arms 1,2, and 3. Biochemical recurrence occurred in 1,2, and 0 patients in arms 1,2, and 3, respectively. Table 1 demonstrates the operative outcomes in all 3 arms.

Table 1 – Operative outcomes:



The authors concluded that these early results might indicate that neoadjuvant therapy before radical prostatectomy can result in a reduction of tumor volume. These early data suggest improved potency preservation without an adverse effect on positive surgical margin rates. However, more data is needed to validate these initial results.

Presented by: Joshua Sterling, MD, Robert Wood Johnson Medical School, New York, NY, USA 

Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020.

AUA 2020: Quality of Life of Prostate Cancer Patients with Testosterone Deficiency Symptoms Before Initiation of Gonadotropin-Releasing Hormone Agonist Therapy, Subgroup Analysis of EQUINOXE Study

( Prostate cancer and testosterone deficiency symptoms increase with age. Therefore, patients may suffer from both conditions, and their quality of life could be significantly reduced.

The EQUINOXE (NCT02630641) is an observational study in prostate cancer patients initiating GNRH agonist therapy and included 492 patients and their partners. The objective of this currently complimentary presented study was to describe the baseline parameters of patients with testosterone deficiency symptoms at baseline.

This was a prospective, multicenter, longitudinal, non-interventional study conducted in France. Patients with histologically confirmed prostate cancer, who were eligible to start GNRH agonist therapy, and their partners were included in this study. Baseline and six-month follow-up data were analyzed, including data from their partners, using various questionnaires. The objective was to evaluate the evolution of the quality of life after six months of agonist hormonal therapy.

Several questionnaires were used, as demonstrated in Table 1.

Table 1 – questionnaires used:


The results demonstrated that there was an improvement in at least 1 of the 4 dimensions of the patient’s WHOQOL-BREF questionnaire (physical, psychological, social, and environmental) in 66.8% of patients. Moreover, there was an improvement in the partner’s quality of life during the 6-month period in 15.2% of partners.

Multivariable analysis revealed that a QLQ-PR25 treatment-related symptoms score >=25/100 at baseline, which is a quality of life questionnaire specific to prostate cancer, was a significant factor of quality of life improvement after a 6-month follow-up (OR 3, 95% CI 1.46-6.17), for patient quality of life, and (OR 5.99, 95% CI 2,40-14,93) for the partner’s quality of life.

Not all patients received hormonal therapy at baseline, and those patients who did not receive treatment but who had treatment-related symptoms at baseline were considered to have testosterone deficiency symptoms.

All dimensions of the WHOQOL-BREF at baseline were rated significantly worse in patients with testosterone deficiency symptoms at baseline than in those without testosterone deficiency symptoms at baseline (Figure 1).

Figure 1- Sub-scores of quality of life (WHOQOL-BREF) questionnaire:


The total score of illness (B-IPQ) and cohesion in the couple (DAS score) were both significantly worse at baseline in patients with testosterone deficiency symptoms (Table 2).

Table 2 – Total score of illness (B-IPQ) and DAS score at baseline:


In conclusion, 26% of the EQUINOXE patients had testosterone deficiency symptoms at baseline. This subgroup analysis demonstrated that patients with testosterone deficiency symptoms at baseline experienced a worse cohesion of the couple at baseline and a lower quality of life than patients who did not have testosterone deficiency symptoms.

Patients with testosterone deficiency symptoms at baseline benefited relatively more from androgen deprivation therapy (GNRH agonists) with regards to their quality of life, as was previously shown in the final analysis of the EQUINOXE study (6-month follow-up).

Lastly, these data suggest a better way to evaluate patients when starting androgen deprivation therapy and enable us to improve personalized supportive care.

Presented by: Stephane Droupy, Chu de Nimes, Université de Montpellier, Nimes, France

Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan, at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020.

AUA 2020: Cardiovascular Risk with GnRH Agonists and Antagonists: Real-world Data from UK Primary Care

( Androgen deprivation therapy in prostate cancer is an effective treatment for a certain period of time and does improve prognosis. However, there is concern over long term side effects, including cardiovascular events. It has been shown that long-term androgen deprivation therapy increases the cardiovascular event rate. 20 to 30% of prostate cancer patients have pre-existing cardiovascular disease, and their prognosis has been shown to be worse as they may have a greater increase in cardiovascular risk when started therapy with androgen deprivation therapy.