www.renalandurologynews.com SEPTEMBER/OCTOBER 2021
■ AUA2021
Renal & Urology News 3
American Urological Association 2021 Annual Meeting
Enzalutamide vs AS Slows PCa Progression Benefit observed in men with low- and intermediate-risk clinically localized prostate cancer AMONG MEN with low- or intermediate-risk prostate cancer eligible for active surveillance (AS), those treated with enzalutamide may benefit from a significant reduction in the risk for cancer progression compared with those undergoing AS, according to findings from a phase 2 open-label exploratory study. The study is the first to assess the efficacy and safety of a novel androgen receptor antagonist as monotherapy in patients with clinically localized low- or intermediate-risk prostate cancer, said lead investigator Neal D. Shore, MD, medical director for the Carolina Urologic Research Center in Myrtle Beach, South Carolina. Enzalutamide was well tolerated and provided significant clinical benefit compared with AS. “Enzalutamide may therefore offer an alternative treatment option in this patient population,” he said. The trial included 227 patients (53% with low-risk and 47% with favorable intermediate-risk disease) randomly assigned to receive 160 mg/d of enzalutamide (114 patients) or to undergo AS (113 patients). Baseline characteristics were similar between study arms. Of the 227 patients, 165 (85 in the enzalutamide group and 80 in the AS arm) completed 1 year of treatment. Baseline
Negative Prostate Biopsy Rates In a phase 2 trial that included men with low- and intermediate-risk prostate cancer, those treated with enzalutamide had a significantly higher rate of negative prostate biopsies at 1 year compared with those on active surveillance. At 2 years, however, the difference in rates was not significant. 40
35.1%
n Enzalutamide n Active surveillance
30 20
14.2%
19.0% 12.0%
10 0
1 Year
2 Years
Source: Shore ND, et al. Enzalutamide in patients with localized prostate cancer undergoing active surveillance: ENACT. Presented at AUA2021. Poster MP62-17.
characteristics were similar between study arms. Of the 227 patients, 165 (85 in the enzalutamide group and 80 in the AS arm) completed 1 year of treatment. Patients had up to 2 years of follow-up. Enzalutamide-treated patients had a significant 46% reduction in pathologic prostate cancer progression risk and 29% decreased risk for PSA progression compared with those undergoing AS. Enzalutamide delayed PSA progression by a median of 6 months vs AS. At 1 year, a significantly higher proportion of patients in the enzalutamide group had a negative prostate biopsy
compared with the AS group (35.1% vs 14.2%). At 2 years, however, although a higher proportion of enzalutamide recipients compared with the AS group had a negative biopsy (19% vs 12%), the difference between the study arms was no longer significant. Enzalutamide recipients were 3.5 times more likely than those in the AS group to have a negative prostate biopsy at 1 year. The odds of a negative biopsy at 2 years did not differ significantly between the groups. Dr Shore’s team defined pathologic progression as an increase in primary or secondary Gleason pattern by more
than 1 or a greater than 15% increase in cancer-positive cores. They defined therapeutic progression as the earliest occurrence of primary therapy for prostate cancer (prostatectomy, radiation, focal therapy, or systemic therapy). Patients with low-risk cancer had stage T1c–T2a disease, a PSA level less than 10 ng/mL, a Gleason score 6 or less, and no nodal involvement or metastasis. Patients with intermediaterisk disease had T2b-T2c disease, a PSA level less than 20 ng/mL, Gleason score of 7 (3+4 pattern), and no nodal involvement or metastasis. Commenting on the findings, Adam S. Feldman, MD, MPH, a urologic oncologist at Massachusetts General Hospital in Boston, who was not involved in the research, said the study cohort is notable for its relatively high proportion of patients with favorable intermediate-risk disease. As the majority of patients with favorable intermediate-risk disease opt for treatment rather than AS, enzalutamide could possibly be an alternative to radical prostatectomy or radiation, Dr Feldman said. He said he would be hesitant to place patients with low-risk or very-lowrisk prostate cancer on a drug with potential side effects when these patients may well be able to avoid treatment anyway. ■
NAC May Improve UTUC Outcomes in Older Patients NEOADJUVANT chemotherapy (NAC) prior to radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) may benefit selected elderly patients and those with locally advanced disease, new study findings suggest. Previous studies have demonstrated that NAC prior to radical nephroureterectomy (RNU) for UTUC improves oncologic outcomes. These outcomes, however, have not previously been explored in the elderly even though the highest incidence of UTUC is among individuals aged 70 to 90 years, Nico C. Grossmann, MD, of the Medical University of Vienna in Austria, and colleagues noted. In a multicenter study that included 170 patients, Dr Grossmann’s team found that elderly patients (defined as those older than the group’s median age of 68 years) who were eligible for
treatment with cisplatin-based NAC prior to radical nephroureterectomy (RNU) may experience pathologic improvements from this multimodal therapy similar to those of their younger counterparts. All study patients had clinically nonmetastatic, high-risk UTUC treated with NAC and RNU. Of the 170 patients, 77 (45%) were older than 68 years. The median follow-up was 29 months. The younger and older groups had similar rates of pathologic objective response and pathologic complete response (51% vs 48% and 10% vs 9%, respectively). Although overall survival was lower in the elderly group, both groups had similar recurrence-free and cancer-specific survival, according to the investigators. “Despite the reluctance to provide systemic therapy in elderly patients,
these patients seem to benefit similarly from cisplatin-based NAC as their younger counterparts,” Dr Grossmann said. “Elderly patients who are ineligible for cisplatin treatment had the lowest response rates and are most likely to benefit from immediate RNU.”
Patients younger and older than 68 years had similar rates of pathologic response. In a separate study of 289 patients with locally advanced UTUC—144 of whom had NAC followed by RNU and 145 who underwent RNU alone (control group)—pathologic downstaging
occurred significantly more frequently in the NAC group than the control group (69% vs 24%), Yuka Kubota, MD, of Hirosaki University Graduate School of Medicine in Hirosaki, Japan, and colleagues reported. The rate of downstaging to pT1 or less disease was significantly higher in the NAC than control group (42% vs 9%). The NAC group, which received 2 to 4 courses of either cisplatin- or carboplatin-based regimens, had a significantly lower rate of lymph node invasion (25% vs 49%). In adjusted analyses, the NAC group had a significant 41% decreased risk for death compared with the control group. The study patients had undergone RNU at 7 hospitals from 2000 to 2020. NAC use increased during the study period from 19% in 2006-2010 to 58% in 2011-2015 and 79% in 2016-2020. ■
