© 2021 MJH Life Sciences and Targeted Oncology-Immunotherapy, Biomarkers and Cancer Pathways. all rights reserved.

© 2021 MJH Life Sciences™, targeted oncology-immunotherapy, biomarkers and cancer pathways. all rights reserved.

A study confirmed that androgen receptor inhibition does not complicate the outcome of robotic prostatectomy for prostate cancer patients.

The analysis of the Phase 2 NEAR trial (NCT03124433) published at the annual meeting of the European Association of Urology in 2021 confirmed that androgen receptor inhibition did not complicate the outcome of robotic prostatectomy for prostate cancer patients.

"It has been previously reported that neoadjuvant androgen deprivation therapy will complicate prostatectomy; [however, data on the effectiveness of neoadjuvant apalutamide before robotic prostatectomy have not been described," said Xinyan Yang of MBBS in the data introduction. "Due to neoadjuvant treatment, we did not encounter any difficulties; there was no excessive blood loss, and fibroproliferative changes appeared in the tissues, making the operation more difficult than usual." Yang is a medical staff and resident of Singapore General Hospital.

The NEAR trial enrolled 25 patients with organ-limited prostate cancer confirmed by biopsy. Recruited patients with intermediate to high-risk diseases defined by D'Amico criteria. Neoadjuvant Apalutamide (Erleada) was administered at a dose of 240 mg per day for 12 weeks, after which all patients underwent robotic radical prostatectomy and pelvic lymph node dissection. In a discussion, Yang pointed out that the surgical technique performed by the researchers on this patient group is no different from their conventional surgery, starting with bilateral seminal vesicle resection.

During the 12-week treatment period, neoadjuvant apalutamide caused a statistically significant decrease in serum prostate-specific antigen (PSA) levels (P <.0001). After prostatectomy, the PSA level further decreased, which was also considered significant (P = .001). In addition, the average quality of life score based on version 3.0 of the European Organization for Cancer Research and Treatment Quality of Life Questionnaire did not significantly decrease (P = .08).

After prostatectomy, according to the International Society of Urological Pathology (ISUP) guidelines, 40% of patients have grade 3 or higher disease, and all patients have at least stage pT2c disease. The average lymph node yield was 24 (range, 4-49), and 73% of patients had negative margin status. Three patients (27%) found a positive surgical margin.

Regarding lymph node status, 70% (n = 21) of patients had N0 and 4 patients had N1. In terms of PSA response after surgery, 84% were at the lowest level (0.5 ng/mL), and 16% were above the lowest level.

The data from the NEAR trial was compared with the results of a prospective analysis of multi-ethnic Asian patients from a single institution who underwent prostatectomy without neoadjuvant apalutamide (n = 725). In terms of perioperative results—estimated blood loss (EBL), length of stay (LOS), catheter time, and complication rates—the results showed that the use of neoadjuvant apalutamide for prostatectomy produced similar results. 1,2

In the neoadjuvant apalutamide study, the average EBL was 198 mL (range, 50-400), while in the study of patients without neoadjuvant apalutamide it was 215 mL (range, 10-2000). The average length of stay in both groups was 3 days. 1,2

The average catheterization time for patients receiving neoadjuvant apalutamide was 8 days (range, 3-14), compared to 7 days for patients who did not receive neoadjuvant therapy (range, 3-72). According to the Clavin-Dindo classification, 80% of postoperative events were classified as 0 in patients who received neoadjuvant apalutamide, compared with 78.5% of patients who did not receive neoadjuvant apalutamide. Similarly, 20% of patients in the neoadjuvant apalutamide group reported a score of 1 or 2, compared to 17.6% in the non-adjuvant group. Finally, 0 patients who received neoadjuvant apalutamide had a Clavin-Dindo classification of 3, 4, or 5, compared with 3.8% of patients who underwent surgery alone (P <.05).

Yang introduced a case study of a 71-year-old Chinese man with no previous medical history. The subject had D'Amico high-risk disease, and the preoperative serum PSA was 43 μg/L. The patient also obtained a Gleason score of 44 (ISUP level 4) through a biopsy, and had clinical T3b bilateral disease.

The subject’s multi-parametric MRI revealed a serious disease involving two prostate lobes, possibly involving extracapsular extension on the right side and involvement of the roots of the right seminal vesicles and neurovascular bundles. The operation starts from the posterior dissection, providing the seminal vesicles and the left vas deferens. Cut open the rectum and prostate fascia to free the rectum. Although he received 12 weeks of neoadjuvant apalutamide treatment, he still retained the anatomical surface and did not increase the tissue pro-fibrosis response.

Use Hem-o-lok clips for pedicle ligation. Yang said that in order to increase the rate of postoperative incontinence, an apical anatomy was carried out to preserve enough urethra length.

In addition, lymph node dissection is routinely performed and bladder neck reconstruction is performed using a handle-type rear racket. In the reconstruction process, the bladder-urethral anastomosis suture method was also used, that is, running with a hub and sutures to ensure a watertight fit.

Yang reported that there was ypT3bN1 and ISUP grade 4 disease during histological examination of the specimen. Of the 47 lymph nodes, 2 were positive for adenocarcinoma. The PSA level was lower than 0.03 μg/L 4 weeks after surgery. "The perioperative results are comparable to the historical series without neoadjuvant therapy," Yang concluded, noting that "neoadjuvant apalutamide is well tolerated, but it is related to decreased libido."

1. Yang XY, Tiwari R, Aslim EJ, etc. The strong inhibition of androgen receptors by neoadjuvant apalutamide will not complicate the outcome of robotic prostatectomy. Published in: The 36th Annual Meeting of the European Association of Urology; July 8-12, 2021; virtual. Abstract V41. Accessed on July 12, 2021. https://virtual.uroweb.org/resource-centre/EAU21/222528/Abstract/

2. Alvin LWX, Gee SH, Hong HH, etc. Oncology results after robot-assisted radical prostatectomy in a multi-ethnic Asian population. J Robot Surgery. 2015;9(3):201-209. doi:10.1007/s11701-015-0516-1