Superior outcomes were observed in men with intermediate-risk prostate cancer who received magnetic resonance (MR)-guided focused ultrasound (MRgFUS) focal therapy than patients in the same population were treated with radical prostatectomy or radiation therapy, demonstrate findings from a phase 2b study (NCT01657942) presented at the 2021 American Urological Association Annual Meeting.

“ExAblate MR-guided focal therapy using real-time MR thermometry preserves urinary incontinence and sexual function and it’s an effective for grade group 2 and 3 prostate cancer cancers are based on 2-year biopsy outcomes,” said lead author Behfar Ehdaie, MD, MS, a urologic surgeon at Memorial Sloan Kettering Cancer Center. “ExAblate MR-guided focus ultrasound may enable men to consider a tissue preserving approach and defer or avoid radical therapy.”

At 24 months, 88% of men had no evidence of grade group 2 or 3 prostate cancer in the treatment area according to targeted prostate biopsy. Additionally, 60% of men had no evidence of grade group 2 or 3 disease anywhere in the prostate gland, including outside of the treatment area. Serum PSA levels decreased by almost 50% after treatment and stabilized after 6 months.

Ehdaie said that men who undergo prostatectomy or radiation therapy often experience significant declines in erectile function and urinary incontinence. Data from a study of 3262 men published in 2020 showed that, at 12 months, about 60% experienced erectile dysfunction following nerve-sparing radical prostatectomy and approximately 50% experienced the same following external beam radiation therapy.

 Men who have intermediate-risk prostate cancer, grade group 2 or 3, are often ineligible for active surveillance or experience early disease progression, up to 40% in findings from the ProtecT trial (NCT02044172), leading to surgery or radiation therapy.

Ehdaie and colleagues explored MRgFUS as an alternative therapy that reduces side effects while maintaining cancer control by targeting areas of no cancer within the prostate gland. He said the ExAblate MR-guided focus ultrasound device delivers targeted high intensity focused ultrasound therapy through the rectum. Ehdaie added that multicenter retrospective studies have shown focal therapy for prostate cancer is safe, and approximately 80% of men require no further prostate cancer-directed treatment.

Investigators evaluated MRgFUS in a single arm, multicenter trial. Men (N = 101) were treated at 7 academic centers and 1 private practice. MRgFUS was delivered focally to the lesion with a margin of normal tissue of greater than or equal to 5 mm based on planning. Treatment was monitored with real-time MR thermometry. Concurrent grade group 1 prostate cancer foci were not treated.

Men with untreated unilateral and more visible, grade group 2 or 3 prostate cancer were eligible. Patients were excluded if they were unable to undergo MRI or had large calcification between the rectum and the planned targeted treatment zone that could interfere with treatment.

Patients underwent targeted and systematic biopsies at 6 and 24 months after treatment, and examinations with quality of life measurements every 3 months.

The primary end points were efficacy and safety. Secondary end points included change in baseline patient-reported quality of life at 24 months.

The average patient age was 63 years and 86% of the cohort was White. The median PSA was 5.7 ng/mL. Eighty-four patients had at least clinical stage T1c disease. Seventy-eight percent of patients were in grade group 2 and 22% were in grade group 3.

Ehdaie said investigators recorded no serious adverse events (AEs). Most minor or moderate AEs self-resolved by 90 days. Two patients had ejaculation disorder and 1 had hematospermia beyond 90 days.

Erectile function scores were slightly worse at 24 months compared with baseline (HR, -3.5; 95% CI, -5.4 to -1.6). Ten (13%) reported no sexual activity and 81% of patients achieved erections adequate for intercourse.

Lower urinary tract symptoms were similar at baseline and 24 months (mean score difference, 1.1; 95% CI, 0.33-1.8).

“Overall, approximately 75% of men were able to achieve functional reactions after treatment at 24 months without starting a new erectile function medication,” Ehadie said. “No patients reported urinary incontinence and the estimated probability of urinary continence over time was excellent.”

Ehadie B, Tempany C, Holland F, et al. MRI-guided focused ultrasound (MRgFUS) focal therapy for intermediate-risk prostate cancer: final results of a phase IIb multicenter study. Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract LBA02-12.

Hoffman KE, Penson DF, Zhao Z, et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy, or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. 

. 2020;323(2):149-163. doi:10.1001/jama.2019.20675

Hamdy FC, Donovan JL, Lane JA, et al. 10-Year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. 

. 2016;375(15):1415-1424. doi: 10.1056/NEJMoa1606220

Guillaumier S, Peters M, Arya M, et al. A multicentre study of 5-year outcomes following focal therapy in treating clinically significant nonmetastatic prostate cancer. 

. 2018;74(4):422-429. doi:10.1016/j.eururo.2018.06.006

Articles

Patients with prostate cancer fared better following treatment with magnetic resonance-guided focused ultrasound focal therapy than with radical prostatectomy or radiation therapy, shows study presented at 2021 AUA Annual Meeting.


 Men with Intermediate-Risk Prostate Cancer Experience Improved Sexual Function, Urinary Continence Following MRgFUS Therapy

Apalutamide (Erleada) was associated with high adherence rates and favorable prostate-specific antigen (PSA) response in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), suggest real-world evidence (RWE) presented at the 2021 American Urological Association Annual Meeting.

The analysis included data for 193 patients from routine urologic practice; investigators stratified results by Black vs non-Black patients. PSA response was defined as a minimum of 50% decline from baseline PSA; adherence was assessed using the medication possession ratio, defined as the number of days of supply within the entire exposure to therapy.

PSA response in the first 6 months after initiating apalutamide was observed in 83.5%, 86.5%, and 84.1% of patients in the overall (n = 176), Black (n = 29), and non-Black cohorts (n = 126), respectively, who had both pre- and post-index PSA measurements. At the 12 months, PSA response was reported in 86%, 93.1%, and 85.9% of patients in the overall (n = 178), Black (n = 29), and non-Black cohorts (n = 128), respectively.

Adherences rates were 93.6%, 90.1%, and 94.5% for patients in the overall (n = 193), Black (n = 33), and non-Black cohorts (n = 138), respectively.

“Apalutamide, a next-generation androgen receptor inhibitor, in conjunction with androgen deprivation therapy was approved by the [FDA] for [patients with] nmCRPC based on the results of randomized SPARTAN clinical study [NCT01946204],” said Benjamin H. Lowentritt, MD, FACS, director of Minimally Invasive Surgery and Robotics, and director of the Prostate Cancer Care Program at Chesapeake Urology in Towson, Maryland. “However, the effectiveness [of the agent] in real-world practice needs further evaluation.”

In the SPARTAN study, patients treated with apalutamide (n = 806) had a median metastasis-free survival of 40.5 months vs 16.2 months for those who received placebo (n = 401; HR, 0.28; 95% CI, 0.23-0.35; P < .001), meeting the primary end point of the study and leading the FDA approval.2 PSA response was an exploratory end point of the study.

Investigators reported that 89.7% of patients treated with apalutamide had a PSA response.

 “Our real-world study showed that PSA response to apalutamide and continuous androgen deprivation therapy was robust and consistent with that in the SPARTAN study,” Lowentritt said.

To conduct the analysis, investigators used electronic medical records collected as part of routine clinical care from 95 US-based urology practices with dispensaries. PSA response and treatment patterns were evaluated from the index date—the first apalutamide dispensation among patients with non-metastatic CRPC—to the end of data availability (October 4, 2019), switch to another first- or second-generation antiandrogen, or death.

Baseline characteristics were evaluated in 12 months preceding the index date.

In this retrospective longitudinal cohort design, 193 patients with non-metastatic CRPC were treated with apalutamide; 33 (17%) were Black, 138 (72%) were non-Black, and 22 (11%) had an unknown racial background. Among the 3 cohorts, most patients (76%) were aged 71 to 90 years.

Evaluated patients had 2 apalutamide prescription fills and 12 months of prior prostate cancer management at baseline.

The mean baseline PSA levels for the overall (n = 190), Black (n = 33), and non-Black groups (n = 135) were 7 ng/mL, 10.5 nh/mL, and 5.6 ng/mL, respectively. PSA doubling times were reported for 90 (46.6%), 16 (48.5%), and 70 patients (50.7%), respectively, and the mean doubling times were 10.8, 10.2, and 10.1 months. The mean baseline testosterone for the overall (n = 146), Black (n = 22), and non-Black patient cohorts (n = 105) was 16.3 ng/dL, 15.1 ng/dL, and 17.3 ng/dL, respectively.

An additional efficacy end point was persistence rate, assessed as the proportion of patients who did not have a specific gap in treatment within a fixed period following the index date. At 6 months, 79.7%, 81.5%, and 80.6% of patients in the overall (n = 153), Black (n = 27), and non-Black cohorts (n = 108), respectively, did not have a gap in treatment over 45 days. Similarly, an over 90-day gap in treatment was not observed in 88.9%, 92.6%, and 87% of patients in the overall, Black, and non-Black groups, respectively.

A numerically higher proportion of Black patients were persistent at 12 months; specifically, 62.7%, 78.9%, and 58.6% of patients did not have an over 45-day gap in treatment in the overall (n = 102), Black (n = 19), and non-Black groups (n = 70), respectively. Correspondingly, an over 90-day gap in treatment was not observed in 69.6%, 78.9%, and 65.7% of patients in the overall, Black, and non-Black groups, respectively.

Lowentritt noted that although Black patients have higher incidence of prostate cancer, they comprised only 6% of the SPARTAN trial population.

“[This study provided] important information on real-word PSA responses in Black men, a population that is typically not well represented,” he concluded.

References
1.	Lowentritt B, Brown G, Kernen K, et al. Real-world effectiveness and treatment adherence of apalutamide in non-metastatic castration-resistance prostate cancer patients. J Urol. 2021;206(suppl 1):e58. doi:10.1097/JU.0000000000001969.08
2.	Smith MR, Saad F, Chowdhury F, et al; Spartan Investigators. N Engl J Med. 2018;378(15):1408-1418. doi:10.1056/NEJMoa1715546

Real-world evidence recently presented at the 2021 AUA Annual Meeting showed that high adherence rates and favorable prostate-specific antigen (PSA) response were observed in men with nmCRPC who were treated with apalutamide. 

Apalutamide Induces Impressive PSA Response and Solid Adherence Rates in Men with nmCRPC

Patients with metastatic castration-resistant prostate cancer (mCRPC) who are obese report better disease specific and overall survival (OS) than patients who are overweight or normal weight, indicate findings from an analysis of three phase 3 clinical trials presented at the 2021 American Urological Association Annual Meeting.

“The BMI effect on cancer-specific mortality was also confirmed as a continuous and as a categorical variable,” said study coauthor Giuseppe Ottone Cirulli, MD, a urology resident of Vita-Salute San Raffaele University in Milan, Italy. “Additionally, the protective effect of BMI is not related to the higher dose of chemotherapy.”

Cirulli said that prior data have demonstrated the correlation between BMI and survival outcomes in prostate cancer. In this study, investigators sought to determine whether BMI among patients with mCRPC is associated with OS and disease-specific mortality.

Investigators identified 1577 patients in the ASCENT2 (NCT00273338), MAINSAL (NCT00988208), and VENICE (NCT00519285) trials, 655 of whom had died by the end of the studies. The median follow-up for survivors was 12 months. The Cox semi-proportional hazard model was utilized to predict for OS, while the competing risks regression was utilized to predict for cancer-specific mortality.

There were adjusted analyses for age, prostate-specific antigen, ECOG, number of metastasis, and prior therapy.

The median age was 69 years, and the median BMI was 28 kg/m2. Investigators analyzed the role of BMI on survival outcomes both as a continuous and categorical variable (<20 vs 20-25 vs 25-30 vs >30 km/m2). A BMI of 30 kg/m2 or greater was considered obese.

BMI emerged as a protective factor for OS both as a continuous variable (HR, 0.96; 

= .015) and as a categorical variable (HR, 0.71; 

= .027). Similarly, BMI’s effect on cancer-specific mortality was confirmed both as a continuous (HR, 0.94; 

= .002) and as a categorical variable (HR, 0.65; 

Cirulli and colleagues selected patients from ASCENT2, MAINSAL, and VENICE because all 3 included men with mCRPC treated with docetaxel. Chemotherapy dose is determined in part by weight, but investigators determined there was no interaction between the BMI categories and the docetaxel dose (all 

In ASCENT2, patients were randomly assigned to 45 μg DN-101, 36 mg/m2 docetaxel, and 24 mg dexamethasone weekly for 3 weeks of a 4-week cycle (n = 476) or 5-mg twice-daily prednisone plus 75 mg/m2 of docetaxel and 24 mg dexamethasone every 3 weeks (n = 477).

The median follow-up for patients alive at last assessment was 11.7 months. The median OS was 17.8 months (95% CI, 16.0-19.5) in the experimental arm and 20.2 months (95% CI, 18.8-23.0) in the control arm (log-rank 

 = .002). Survival remained poorer in the experimental arm even after adjusting for baseline variables (HR, 1.33; 

In MAINSAL, chemotherapy-naïve patients with progressive mCRPC were randomized to 75 mg/m2 docetaxel on day 1 and 5 mg twice-daily prednisone on days 1 to 21 and either 25 mg once-daily lenalidomide (n = 533) or once-daily placebo (n = 526) on days 1 to 14 of each 21-day treatment cycle.

The median OS was 17.7 months (95% CI, 14.8-18.8) in the lenalidomide group and was not reached in the placebo group (HR, 1.53; 95% CI, 1.17-2.00; 

= .0017). The trial was subsequently closed early due to futility.

In VENICE, 1224 chemotherapy-naïve patients with adequate organ function were assigned to 75 mg/m2 docetaxel every 3 weeks plus 5 mg twice-daily oral prednisone (5 mg twice daily). They were then randomly allocated to 6 mg/kg of aflibercept (Eylea; n = 612) or placebo (n = 612) every 3 weeks. Results showed that the median OS was 22.1 months (95.6 CI, 20.3-24.1) in the aflibercept group vs 21.2 months (95.6% CI, 19.6-23.8) in the placebo group (HR, 0.94; 95.6% CI, 0.82-1.08; 

Martini A, Cirulli GO, Gandaglia G, et al. The obesity paradox in metastatic castration resistant prostate cancer. Presented at: the 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract PD05-01.

Scher HI, Jia X, Chi K, et al. Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. 

. 2011;29(16):2191-2198. doi:10.1200/JCO.2010.32.8815

Petrylak DP, Vogelzang NJ, Budnik N, et al. Docetaxel and prednisone with or without lenalidomide in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (MAINSAIL): a randomised, double-blind, placebo-controlled phase 3 trial. 

. 2015;16(4):417-425. doi:10.1016/S1470-2045(15)70025-2

Tannock IF, Fizazi K, Ivanov S, et al. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. 

. 2013;14(8):760-768. doi:10.1016/S1470-2045(13)70184-0

Obese men are more likely to have improved overall survival following treatment for mCRPC than man who are overweight or normal weight, analysis finds. 

Higher BMI Linked to Superior Survival in mCRPC

Yoga can promote an improved quality of life among patients with prostate cancer, show phase 2 trial findings presented at the 2021 AUA Annual Meeting. In addition, the meditative activity may result in antitumor immune responses and reduced inflammation in patients undergoing prostatectomy.

Yoga has a direct effect on the vagus nerve, which can shape how a person thinks, remembers, and feels. And patients with prostate cancer have a 20% to 30% incidence and prevalence of depression and anxiety.

In previous studies, yoga has demonstrated an improved quality of life for patients with cancer, as well as lower inflammation. Additionally, newer, emerging data has demonstrated that mindfulness exercises, such as yoga, can cause the frontal and limbic parts of the brain to structurally change.

“However, if you look at hierarchy of evidence, most data on immune benefits of yoga is from small series and case reports, no such data exists for prostate cancer. Given these findings of improvement in quality of life with yoga, we started looking at [the] role of yoga in prostate cancer,” said Dharam Kaushik, MD, associate professor in the department of urology at the University of Texas Health, San Antonio, during the presentation of the data.

The primary outcomes of this clinical trial [NCT02620033] was self-reported outcomes of quality of life at baseline, and 6 weeks. Secondary outcomes included immune cell status and cytokine levels, also at baseline and 6 weeks.

“We wanted to evaluate the quality of life from multiple vantage points, therefore we utilized 4 different quality of life questionaries,” Kaushik mentioned. Self-reported outcomes were assessed by the Expanded Prostate Index Composite (EPIC), Functional Assessment of Cancer Therapy-Prostate (FACT-P), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Five Facets of Mindfulness Questionnaire (FFMQ).

The study consisted of 30 men who were newly diagnosed with localized prostate cancer and scheduled for a radical prostatectomy. Patients were randomized to either yoga (n = 15) or standard of care (n = 15). And patients in the yoga group, performed the activity for 60 minutes twice a week for 6 weeks before their prostatectomy and 3 to 6 weeks after.

Yoga “meaningfully” improved EPIC-sexual scores, FACIT-F, FACT general and FACT-P. In substratification, there were improvements in sexual, physical, and social well-being in the yoga group.

Additionally, participants in the yoga group demonstrated increased numbers of CD4+ (

There was also an increase in the natural killer cells IFNNK (

 = .041), “indicating a robust immune response,” Kaushik added.

Yoga also had an enhanced effect on antitumor activity, decreasing the numbers of regulator T-cells and myeloid-derived suppressor cells: CD11b+CD33+ (

There was also a decrease in cytokine cells including, G-CSF (

 = .032), which had shown to activate production endothelial cell and cytokines. Additionally, there was a decrease in MCP-1 (

 = .044), which are associated with proception against dementia, and FLt-3L (

 = .053) which has been linked to reducing chronic inflation, Kaushik mentioned.

The benefits demonstrated in this study require further investigation, the authors concluded in the abstract.

Kaushik D, Shah P, Mukherjee N, et al. A phase 2 randomized clinical trial of yoga in men with prostate cancer. Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract LBA02-03.

Yoga has a positive impact on the vagus nerve, which influences how people think, remember, and feel, and therefore can improve the mental well-being of patients with prostate cancer. 

American Urological Association Annual Meeting

Men with Intermediate-Risk Prostate Cancer Experience Improved Sexual Function, Urinary Continence Following MRgFUS Therapy

Apalutamide Induces Impressive PSA Response and Solid Adherence Rates in Men with nmCRPC

Higher BMI Linked to Superior Survival in mCRPC

Yoga Encourages Antitumor Response, Boosts Quality of Life in Patients with Prostate Cancer