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The independent specialty pharmacy Biologics by McKesson was designated as a provider of the prostate cancer drug relugolix (Orgovyx).

Earlier this month, Myovant Sciences, the developer of relugolix, officially launched the GnRH receptor antagonist in the United States, making it available through authorized specialty distributors.

The FDA approved relugolix in December 2020 for the treatment of patients with advanced prostate cancer. The approval was based on data from the phase 3 HERO study, which showed that 96.7% of patients randomized to relugolix maintained castration through 48 weeks, compared with 88.8% of patients receiving leuprolide (

“We are pleased to provide this new prostate cancer therapy with demonstrated robust efficacy and safety, all in one daily pill,” Ashleigh Burdette, senior director of Clinical Innovation at Biologics, stated in a press release. “The COVID-19 pandemic has highlighted the importance of oral treatments for patients, especially those who may experience difficulties and risks associated with traveling to receive treatments.”

The open-label international phase 3 HERO trial included 930 patients treated at 155 clinical sites. The median patient age was 71 years (range, 47-97), with 28.6% of patients being aged ≥75 years. Overall, 31.7% of patients had metastatic disease, 15.5% of patients had a Gleason score of 5-6, 38.6% of patients had a Gleason score of 7, and 43.1% of patients had a Gleason score of 8-10. Half (50.2%) of patients had evidence of biochemical or clinical relapse after local primary intervention with curative intent.

The median PSA level at baseline was 10.8 ng/ml and the average testosterone level at baseline was 427.5 ± 156.2 ng/ml. The ECOG performance status was 0 in 88.1% of patients, 11.9% of patients, had prior androgen-deprivation therapy, and 30.3% had prior radiotherapy.

Patients were randomized in a 2:1 ratio to relugolix at 120 mg orally once daily or leuprolide injections every 3 months. Treatment was administered for 48 weeks, with a primary end point of sustained testosterone suppression to castrate levels (<50 ng/dL) through 48 weeks.

On day 4 of treatment, 56% of the relugolix cohort had castrate levels of testosterone versus 0% of the leuprolide group. On day 15, the rates were 98.7% versus 12%, respectively. Also on day 15, 79.4% of the relugolix arm had a confirmed PSA response, compared with 19.8% of patients on the leuprolide arm (

Relugolix was associated with a 54% lower risk of major adverse cardiovascular events compared with leuprolide (HR, 0.46). Major adverse cardiovascular events occurred in 2.9% of the relugolix arm compared with 6.2% of the leuprolide cohort. The study defined major adverse cardiovascular events as nonfatal stroke or myocardial infarction, or death due to any cause.

In the press release, Biologics noted that physicians can submit prescriptions for relugolix pharmacy via phone, fax, or electronic prescription.

1. Shore ND, Saad F, Cookson MS, et al. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. 

. 2020;382(23):2187-2196. doi: 10.1056/NEJMoa2004325

2. ORGOVYX (relugolix), the First FDA-Approved Oral Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist for Advanced Prostate Cancer, Available at Biologics by McKesson. Published online January 21, 2021. Accessed January 21, 2021. https://bit.ly/2Y2LD2A.

Articles

The GnRH receptor antagonist was approved by the FDA in December 2020 for the treatment of patients with advanced prostate cancer. 

Specialty pharmacy designated as provider of relugolix for prostate cancer

Adding an extra dose of external-beam radiation therapy (EBRT) to the standard EBRT improved biochemical disease-free survival (bDFS) in patients with localized prostate cancer, according to findings from the phase 3 FLAME study published in the 

The focal boost was delivered directly to the intraprostatic lesion visible on multiparametric magnetic resonance imaging (mpMRI). At 5 years, the bDFS rate was 92% with the focal boost compared to 85% with standard EBRT alone (HR, 0.45;

The added bDFS came without negatively affecting safety and quality of life. The cumulative incidence of late genitourinary toxicity grade ≥2 was 23% with standard treatment versus 28% with the focal boost. The cumulative incidence of late gastrointestinal toxicity grade ≥2 was 12% versus 13%, respectively. Also, there were only small, statistically insignificant differences in health-related quality of life between the 2 arms.

“The radiation boost halved the percentage of men presenting with raised PSA levels over the first 5 years after treatment: from 15% to 8%,” radiation oncologist and research leader Linda Kerkmeijer, MD, of UMC Utrecht and Radboudumc, stated in a press release. “The radiation boost did not lead to additional side effects, which is an important outcome.”

Between 2009 and 2015, the single-blind FLAME (Focal Lesion Ablative Microboost in Prostate Cancer) study enrolled 571 men with localized intermediate- or high-risk prostate cancer. Patient characteristics were well balanced between the 2 study arms. Across the overall population, the mean age was 70 years.

Patients were randomized in a 1:1 ration to receive standard treatment alone (287 patients) or standard treatment plus the focal boost (284 patients). Standard treatment was conventionally fractionated EBRT comprising 77 Gy in 35 fractions of 2.2 Gy to the entire prostate.

The additional radiation in the experimental arm consisted of a simultaneously delivered integrated focal boost to the macroscopic tumor as visible on mpMRI. The boost was up to 95 Gy, comprising 35 fractions of up to 2.7 Gy. If necessary, investigators reduced the boost to comply with prespecified organs at risk (OAR) constraints.

The median follow-up time was 72 months. Five year bDFS was the primary end point. Secondary end points consisted of DFS, distant metastases-free survival, prostate cancer–specific survival, overall survival, toxicity, and health-related quality of life.

“Our results can benefit a substantial number of men,” radiation oncologist Floris Pos, MD, of the Netherlands Cancer Institute, stated in the press release. “Every year, in the Netherlands, we give radiation therapy to hundreds of men who may qualify for this treatment. This could prevent a lot of trouble: for our patients, cancer recurrence often means uncertainty, diagnostic examinations, and intense treatments like surgery or hormone therapy.”

1. Kerkmeijer LGW, Groen VH, Pos FJ, et al. Focal boost to the intraprostatic tumor in external beam radiotherapy for patients with localized prostate cancer: results from the FLAME randomized phase III trial [published online ahead of print January 20, 2021]. 

2. Radiation boost lowers risk of prostate cancer recurrence. Published online January 20, 2021. Accessed January 21, 2021. https://bit.ly/2KA6J54.

The boost improved biochemical disease-free survival without negatively affecting safety and quality of life.

Focal radiation boost improves outcomes in prostate cancer

Prostate cancer-related suicide decreased during the past 2 decades, according to an American Cancer Society (ACS) study published in the 

Journal of the National Cancer Institute 

The study assessed overall trends in cancer-related suicide and determined that across all tumor types, there was a 2.8% decline per year in cancer-related suicide. In prostate cancer specifically, there was a 5.1% decline per year.

The ACS investigators, led by Xuesong Han, PhD, senior principal scientist, Health Services Research, reviewed data from the Centers for Disease Control and Prevention’s Multiple Cause of Death database, 1999-2018. The database compiles information based on death certificates for US residents. Each death certificate provides “a single underlying cause of death, up to twenty additional multiple causes, and demographic data.”

Overall, 738,743 suicides occurred during the 2-decade time frame, 6487 (0.9%) of which were determined to be cancer-related. The most common cancer types among these suicides were lung and bronchus (18.2%), prostate (15.4%), colon and rectum (9.1%), lymphoma and leukemia (7.4%), and head and neck (6.7%).

Among patients with lung and bronchus, lymphoma and leukemia, and head and neck tumors, cancer-related suicides declined 4.7%, 2.6%, and 3.7%, respectively.

There were also large declines in suicide rates among individuals who were aged 65-74 (-3%), aged 75-84 (-3%), male (-3%), and living in urban areas (-3.5%).

The researchers also assessed overall suicide rates over the same 20-year period. In contrast to the decline in cancer-related suicides, the overall suicide rate increase by 1.7% per year. There were significant increases across most subgroups, including all age groups ≤75 years, males, females, all census regions, urban areas, and rural areas.

“Using comprehensive death certificate data, we identified a decreasing trend of cancer-related suicide during the past 2 decades, despite the continuous increases in overall suicide rates in the United States. We observed the largest declines in cancer-related suicide rates among high-risk populations, including male, older age, and certain cancer types such as lung, prostate, and head and neck cancers,” Han et al wrote in their conclusion.”

“Although no causal relationship can be established, our findings suggest an evolving role of psycho-oncology care and palliative and hospice care given the promotion and increased utilization of these services among cancer patients during this period,” added the authors.

1. Cancer-Related Suicide Declined in the U.S. During the Past Two Decades. American Cancer Society. Posted online January 19, 2021. Accessed January 20, 2021. https://bit.ly/3iIfp6h.

2. Han X, Hu X, Zhao J, Ma J, Jemal A, Yabroff KR. Trends of Cancer-Related Suicide in the United States: 1999-2018. 

JNCI: The Journal of the National Cancer Institute;

3. Multiple Cause of Death database, 1999-2019. Centers for Disease Control and Prevention. Accessed January 20, 2021. 

The trend in prostate cancer aligns with an overall decline in cancer-related suicide across all tumor types. 

Prostate cancer–related suicide declined over the past 20 years

paper, Sporadic compared to recurrent urinary tract infections: Considerations for urogynecologic patients, for which she served as a study author. Bradley is an assistant professor in the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh.

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Acute urinary retention is not uncommon among men who undergo placement of a proprietary transobturator sling (AdVance) for management of postprostatectomy stress urinary incontinence. Still, it is rarely persistent, and it is not predicted by findings from preoperative urodynamic studies, according to the results of a recently published retrospective study.

“Urodynamic studies are often performed prior to surgical intervention for postprostatectomy stress urinary incontinence, but their ability to predict urinary retention following male sling placement is unknown,” said Eric S. Rovner, MD, study investigator and professor of urology, Medical University of South Carolina, in Charleston.

“The results of our study, which to our knowledge is the largest to date to assess postoperative urinary retention following AdVance Sling placement, suggest that if urodynamic studies are being done preoperatively ONLY with the aim of predicting retention, then this investigation is probably not needed. Nevertheless, urodynamics studies still have a role if their purpose is to assess other issues, such as filling abnormalities,” he told 

The study included 391 patients who underwent placement of the AdVance Sling during the years 2007 to 2019. Approximately three-fourths of the patients (n=303, 77.5%) had preoperative urodynamics performed. Median follow-up for the entire cohort was 18.1 months.

Acute urinary retention, defined as an inability to urinate or elevated postvoid residual (PVR) after the first removal of the urethral catheter resulting in an invasive intervention, occurred in 55 (14.1%) men. The majority of those patients were recatheterized (87%), and the rest were treated with clean intermittent catheterization.

Three-fourths of the patients with acute urinary retention had resolution of the problem by their second postoperative visit. Among the 13 patients whose urinary retention persisted, 6 patients, representing 1.5% of the total cohort, had chronic urinary retention at their last follow-up visit. All 6 men were being treated with clean intermittent catheterization.

Comparisons of the preoperative characteristics in the groups with and without acute urinary retention showed no statistically significant differences in their demographics, comorbidities, previous interventions, radical prostatectomy approach, or incontinence severity. Within the subgroup that had urodynamics studies, there were no significant differences between men with and without acute urinary retention in average maximum flow rate (Qmax), detrusor pressure at Qmax (PdetQmax), PVR, bladder contractility index (calculated using the formula PdetQmax + 5 x Qmax), or presence of impaired contractility (defined as BCI <100).

Mean time to initial catheter removal was significantly shorter in men who developed acute urinary retention than in those who did not (2.8 vs 4.6 days; 

= .002). In a univariate regression analysis, earlier postoperative catheter removal was the only explored factor that independently predicted postoperative acute urinary retention. The risk was 17% lower in men whose urinary catheter was kept in longer than 2 days after the sling procedure compared with the group that had an earlier void trial (

“Neither impaired bladder contractility nor abnormal voiding detrusor activity (absence of detrusor contraction during pressure flow, presence of Valsalva voiding or low detrusor pressure at maximum flow) were predictive of acute urinary retention following sling placement,” Rovner said.

Rovner noted that the study has several strengths. These include its multicenter design, a large patient population with a significant proportion of men who had preoperative urodynamics studies, and significant follow-up time.

But the study also has limitations, some of which are inherent to both its retrospective and multicenter design. Additionally, the version of the male sling that was the focus of the study is no longer commercially available.

“Preliminary work suggests that the urinary retention rate following placement of the currently marketed AdVance XP Male Sling System may be slightly higher than the version used in our study. The difference is speculative, however, because there are no direct comparisons,” Rovner said. “It would be worthwhile, therefore, to conduct a prospective study of retention following placement of the newer version of the sling.”

1. Zheng Y, Major N, Silverii H, et al. Urinary retention after AdVance Sling: a multi‐institutional retrospective study. 

Published online December 21, 2020. doi:10.1002/nau.24591

Acute urinary retention is not uncommon among men who undergo placement of a proprietary transobturator sling (AdVance) for management of postprostatectomy SUI. Still, it is rarely persistent, according to a recent study.

Study evaluates acute urinary retention after sling surgery for management of post-RP SUI

Androgen-deprivation therapy (ADT) is unlikely to reduce the risk of COVID-19 infection in men with prostate cancer, according to a cohort study published in the 

The analysis included nearly 1800 men with prostate cancer from a prospective registry of men tested for COVID-19. Using multivariable analysis, the investigators found that the risk of COVID-19 infection was the same, regardless of whether or not the patient had received ADT (odd ratio, 0.93; 

The study contradicts an Italian study published in 2020 which suggested that men with prostate cancer treated with ADT had a significantly reduced likelihood of COVID-19 infection than men not treated with ADT.

“Androgen deprivation therapy does not appear to be protective against COVID-19 infection,” the author wrote.

Overall the study population comprised 1779 men with prostate cancer, of whom 5.7% (102 patients) tested positive for COVID-19 and 17.1% (304 patients) were receiving ADT.

Among the ADT subgroup, 5.6% of patients were COVID-19 positive. This compared to 5.8% among patients not receiving ADT.

Patient characteristics showed that men receiving ADT were more likely to have smoked (68.1% vs 59.3% among patients not receiving ADT; 

 .005), were older (75.5 vs 73.8 years, respectively; 

 = .009), and were more likely to have taken steroids (43.8% vs 23.3%, respectively; 

The researchers also noted that additional factors linked to a higher risk of COVID-19 infection/severity were equally distributed between the ADT group and those not receiving ADT. These included asthma, heart failure, immune suppressive disease, diabetes mellitus, hypertension, and coronary artery disease.

In the previously reported Italian study, use of ADT in patients with prostate cancer was associated with a significantly decreased risk of contracting COVID-19 both compared with men not receiving ADT (OR, 4.05), as well as compared with patients in the study who had any other cancer type (OR, 4.86).

The Italian researchers developed a potential explanation for this apparent “protective” effect of ADT based on 

, an androgen regulated co-factor for COVID-19 cell entry. The investigators hypothesized that the downregulation of 

 by ADT may protect the patient against COVID-19 infection.

 did not corroborate this theory.

“In men with prostate cancer ADT did not protect against SARS-CoV-2 infection. These results do not confirm the experience in Northern Italy. Routine use of ADT in patients at risk for or affected by COVID-19 is not warranted in the absence of controlled clinical trials showing benefits for prevention, mitigation of disease severity or improved survival. We eagerly await the results of ongoing trials testing antiandrogen agents in various stages of this disease,” the authors wrote in their conclusion.

1. Klein EA, Li J, Milinovich A, et al. Androgen deprivation therapy in men with prostate cancer does not affect risk of infection with SARS-CoV-2. J Urol. 2021;205(2):441-443. doi: 10.1097/JU.0000000000001338

2. Montopoli M, Zumerle S, Vettor R et al: Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). 

. 2020;31(8):1040-1045. doi: 10.1016/j.annonc.2020.04.479

The study contradicts the findings from an Italian study published in 2020. 

ADT does not lower COVID-19 risk in men with prostate cancer

The FDA has granted a Fast Track designation to padeliporfin Immune Photo Activated Cancer Therapy (ImPACT) for the treatment of adult patients with low-grade and unifocal high-grade upper tract urothelial cancer (UTUC), according to Steba biotech, the developer of the investigational treatment.

The padeliporfin ImPACT platform involves the intravenous delivery and activation of the photosensitive drug padeliporfin. The drug is delivered intravenously and is activated by a non-thermal light delivery system that uses a lower energy laser light channeled through optical fibers.”

 The minimally invasive approach enables targeted ablation of the tumor. The treatment was initially explored in prostate cancer and is now being investigated in UTUC and other solid tumors.

Padeliporfin ImPACT has shown positive initial efficacy in prostate cancer and a phase 1 UTUC trial. In December 2020, Steba received FDA clearance on an Investigational New Drug (IND) application, permitting the launch of a phase 3 study of padeliporfin ImPACT in patients with low-grade UTUC.

The FDA’s Fast Track designation is designed to expedite the review and development of novel treatments that will fill an unmet medical need.

"Momentum is building towards unlocking the significant potential of padeliporfin ImPACT in a range of solid tumors—first with the IND green light and now Fast Track designation. In the last nine months, under the new leadership team, we have transformed the organization with a bold strategy and focused execution,” Barak Palatchi, CEO of Steba, stated in a press release. “Achieving these important regulatory milestones in quick succession is a powerful acknowledgement of the technology and will accelerate the pace by which we can make padeliporfin ImPACT available for people living with cancer."

A major breakthrough in the UTUC armamentarium came in April 2020 when the FDA approved Jelmyto (mitomycin gel) as the first therapy to treat low-grade UTUC.

According to the FDA, UTUC includes a small subset of urothelial tumors that occur in the lining of the kidney or the ureter. The low-grade subtype of UTUC is most commonly noninvasive and confined to the kidney or ureter; however, these tumors frequently recur.

Overall about 6000 to 8000 new cases of low-grade UTUC occur annually in the United States. Despite the major breakthrough with Jelmyto, there remains a high unmet need for novel UTUC treatments.

"There is currently a high unmet medical need in UTUC, given the clinical aim to preserve the patient's kidney, rendering surgery as a last resort. Good initial efficacy data from the phase 1 clinical trial in patients with UTUC, coupled with strong safety and efficacy data previously obtained in prostate cancer, make us confident that padeliporfin ImPACT has the potential to be a well-tolerated, safe and efficacious treatment in UTUC and other cancer indications," Dr David Perry, head of Steba R&D, stated in the press release.

1. FDA Grants Fast Track Designation to Padeliporfin ImPACT for Steba biotech. Posted online January 17, 2020. Accessed January 19, 2021. https://prn.to/3sI4iOY.

2. Steba biotech. A Novel Treatment Path. Accessed January 19, 2021. https://www.stebabiotech.com/technology-innovation.

3. FDA Approves First Therapy for Treatment of Low-Grade Upper Tract Urothelial Cancer. Posted online April 15, 2020. Accessed January 19, 2021. https://bit.ly/2XUxWCD.

The investigational padeliporfin ImPACT platform involves the intravenous delivery of the photosensitive drug padeliporfin, which is then activated by a non-thermal light delivery system.

FDA grants Fast Track designation to novel treatment for UTUC

Mark Painter is CEO of PRS Urology SC in Denver.

I read that G2211 was delayed by 3 years. Can you explain?

The 2021 Medicare Physician Fee Schedule (MPFS) Proposed Rule included the new Healthcare Common Procedure Coding System (HCPCS) add-on code GCP1X, used to better describe the work associated with visits that are part of ongoing, comprehensive primary care, and/or visits that are part of ongoing care related to a patient’s single, serious, or complex chronic condition. This code could be used by specialists such as urologists who manage complex chronic conditions and may be added to any outpatient evaluation and management service level (99202-99215). This code was resequenced as G2211 in the final rule, released on December 1, 2020.

Code G2211’s description reads, “Visit complexity inherent to evaluation and management associated with medical care services that serve as the continuing focal point for all needed health care services and/or with medical care services that are part of ongoing care related to a patient’s single, serious condition or a complex condition.” This code was valued at 0.33 work relative value units, with a payment of around $16. However, on December 27, 2020, the Consolidated Appropriations Act was passed, which made a number of changes, including a 3.75% increase in MPFS payments for the calendar year 2021, a continued suspension of the 2% payment adjustment (“sequestration”) through March 31, 2021, and a delay of implementation of the G2211 until 2024.

What does this mean? Due to the sheer volume of use of G2211 that was expected to be utilized by providers, these dollars went back into the conversion factor. The Centers for Medicare & Medicaid Services (CMS) therefore recalculated the conversion factor to $34.89. This updated conversion factor represents a 3.3% drop instead of the 10.2% drop included in the final rule. Those who were expected to be significantly impacted by the greater than 10% drop in the conversion factor, such as those who provide a significant number of surgical procedures over office visits, were subject to a reprieve. Urology as a specialty is not expected to be adversely expected. The American Medical Association has projected the same 8% increase in overall revenue for urology in 2021 over 2020. CMS had not yet issued its projections at the writing of this article.

Medicare released an updated relative value unit (RVU) file on December 29, 2020, and an updated RVU file on January 5, 2021. Code G2211 was not included in either file. At this point, we would take this to mean that reporting G2211 will not only result in no payment for the code, but the claim may be rejected considering code G2211 as not valid. The code G2211 is, however, included in the most recent HCPCS file, released on January 3, 2021, so it may not block processing. We would recommend not submitting code G2211 to be safe.

Send coding and reimbursement questions to Rubenstein and Painter c/o

Questions of general interest will be chosen for publication. The information in this column is designed to be authoritative, and every effort has been made to ensure its accuracy at the time it was written. However, readers are encouraged to check with their individual carrier or private payers for updates and to confirm that this information conforms to their specific rules.

Recent legislation appears to have delayed implementation of the new code.

What is the status of chronic condition code G2211?

The FDA has approved the combination regimen of nivolumab (Opdivo) plus cabozantinib (Cabometyx) as a frontline treatment for patients with advanced renal cell carcinoma (RCC).

The approval is based on findings from the phase 3 CheckMate-9ER trial (NCT03141177). Study results showed that the combination reduced the risk of disease progression or death by 49% versus sunitinib (Sutent) in treatment-naïve patients with advanced RCC, with a median progression-free survival of 16.6 months versus 8.3 months, respectively (HR, 0.51; 

Additional findings showed that, at a median follow-up of 18.1 months, the median overall survival was not reached in either arm, and there was a 40% reduction in the risk of death with the combination (HR, 0.60; 

“This combination of cabozantinib and nivolumab significantly improved key efficacy measures compared to sunitinib—progression-free survival, overall survival, and objective response rate—while showing a low rate of treatment discontinuations due to side effects. The therapeutic benefit demonstrated in CheckMate -9ER and quality of life measures explored emphasize the role of this combination for patients with advanced kidney cancer,” Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School, stated in a press release. “With this important FDA approval, the combination is poised to become a standard in newly diagnosed metastatic kidney cancer.”

In the international, randomized, phase 3 CheckMate-9ER trial, 651 patients with advanced RCC received the combination of nivolumab and cabozantinib (n = 323) or sunitinib (n = 328) in the first-line setting. Patients must have had previously untreated advanced or metastatic disease, a clear cell component, and any International Metastatic RCC Database Consortium (IMDC) risk score.

The combination demonstrated a benefit across numerous subgroups, including age, sex, PD-L1 expression, bone metastases, IMDC risk group, and geographic region.

The objective response rate (ORR) was also doubled with nivolumab/cabozantinib in this setting compared with sunitinib, at 55.7% versus 27.1%, respectively (

 <.0001). In the combination arm, the complete response (CR) rate was 8.0%, the partial response (PR) rate was 47.7%, and the stable disease (SD) rate was 32.2%. Additionally, 5.6% of patients had progressive disease (PD) and 6.5% were not evaluable or not assessed. In the sunitinib arm, the CR, PR, and SD rates were 4.6%, 22.6%, and 42.1%, respectively. Moreover, 13.7% of patients had PD and 17.1% of patients were not evaluable or not assessed.

Regarding safety, the incidence of the most common, any-grade and high-grade treatment-related adverse events (TRAEs) were similar in both arms. More than 50% of patients on the combination required dose reductions of cabozantinib due to adverse effects (AEs). TRAEs led to treatment discontinuations in 15.3% of those in the nivolumab/cabozantinib arm and in 8.8% of those on sunitinib. Specifically, 3.1% of patients discontinued both nivolumab and cabozantinib due to AEs, 5.6% discontinued only nivolumab, and 6.6% discontinued only cabozantinib.

The overall rate of serious AEs was similar between the 2 groups; however, liver toxicity was more common with cabozantinib/nivolumab. Nineteen percent of patients on the combination required corticosteroids due to immune-related AEs, 4% of whom needed corticosteroids for at least 30 days.

Cabozantinib was approved by the FDA in December 2017 for use in previously untreated patients with advanced RCC. The FDA approved nivolumab in November 2015 for use in patients with metastatic RCC who progressed on an angiogenesis inhibitor. Nivolumab also has an FDA-approved RCC indication in the frontline setting for use in combination with ipilimumab (Yervoy) as a treatment for intermediate- and poor-risk patients with advanced disease.

1. Exelixis Announces U.S. FDA Approval of CABOMETYX® (cabozantinib) in Combination with OPDIVO® (nivolumab) as a First-Line Treatment for Patients with Advanced Renal Cell Carcinoma. Published online January 22, 2021. Accessed January 22, 2021. https://bwnews.pr/3c2w2bf. 

2. Choueiri TK, Powles T, Burotto M, et al. Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial. 

The approval is based on data from the phase 3 CheckMate-9ER trial. 

FDA approves nivolumab/cabozantinib combo for frontline kidney cancer

Karen Nash is a medical reporter and media consultant based in Monroeville, PA.

 reached out to 3 urologists (selected randomly) and asked them each the following question: Do you prefer dusting or basketing when removing kidney/ureteral stones?

“I like a combination. Dusting creates less risk of injuring the ureter, reducing fragment size, so they don’t get stuck. It’s nice to have pieces for analysis so you can determine composition and figure out what to do in terms of prevention. Also, information is power, and most patients want to know the type of stone they have. Often, I dust as much as I can, basketing a small fragment to analyze. Fragments left after dusting sometimes aren’t always large enough to grab. Dusting is easier because it allows those fragments to pass without damage to the ureter.

Location makes a difference, however, especially if you have a larger stone up in the renal pelvis. Those are more amenable to dusting because no one wants to make a lot of trips up and down the ureter removing fragments. Dust them as small as possible and let that debris pass spontaneously.

Lower ureteral stones are easier to remove at times. I really don’t have to dust them as much to achieve a stone free status. Higher in the renal pelvis, dusting expedites the procedure because you don’t have to take the scope in and out as many times.

Everything comes down to patient selection and location of the stones. If it’s a smaller stone in the lower ureter, basketing it and pulling it out may be quicker than dusting it.”

“I’m doing a lot more dusting. I do a hybrid, but because we have a new-generation laser, the dusting really changed and became a lot faster.

I work in 2 hospitals. Last year, we got a new holmium at one, then we got a thulium laser at the other. They’re both much faster than what I had before. They use much higher frequencies to dust. They’re also a lot more efficient.

With lasers, sometimes, you would still have quite large fragments. With newer lasers, they turn everything to dust, and often, there’s nothing left.

I’ll still do a hybrid at times. If it’s a distal stone, I’ll out basket it because then I know for sure it’s completely out. If I have a ureteral access sheath, I’ll basket, easily removing everything.

You can reliably basket everything; then, you’re guaranteed to have 100% stone clearance rate. With an access sheath, you can go in and out of the kidney easily and get everything out.

I try to leave a fragment for stone analysis if I can, but I recently had a case with this new laser where I dusted, put a basket in, and nothing came out. I wasn’t able to get a stone analysis, but we can always do a 24-hour urine, so it’s not a terrible loss.”

“I prefer dusting. With basketing, stones can still get stuck or create tears in the ureter, whereas if you dust the stone, you can blow the pieces out more gently.

We probably all do some sort of combination, dusting the stone down until it’s an appropriate size where there won’t be tugging and pulling, and you can basket it through the ureter without scraping the sides.

The location of the stone also helps determine the technique choice. If it’s small and up in the kidney, you may basket it and know you’ve gotten it, whereas if the stone is already stuck in the ureter, you know you’ll have to laser it before basketing.

There are potential problems relying on just 1 method. Just dusting risks leaving microparticles that can form a new stone, and it’s a bit more time-consuming, whereas with the basket, it’s gone. But you have to ensure you can get through the entire ureter without pulling or scraping if you’re just basketing.

A significant influence from my residency, while I was a second year, my attending basketed a stone and pulled so hard he pulled the ureter down—which is probably why I’m not a fan of basketing.

Although it’s nice to have a sample to determine the stone’s composition, patients can make different stones every time, depending on what’s going into their urine. Mrs. Jones may have too much oxalate, whereas Mrs. Smith may lack citrate. So although the composition is important, doing the 24-hour urine test to advise the patient on dietary measures is really more important. So I don’t always treat the patient on a basketed sample anyway.”

"Everything comes down to patient selection and location of the stones," says one urologist.