375-miRNA expression and neoadjuvant therapy in high risk prostate cancer

e543 Background: The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low-dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). The aim of this study was to assess whether neoadjuvant LHRH+EMP confers an oncological benefit for high-risk Pca compared to extended lymph node dissection (e-PLND). Methods: The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at 4 institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The neoadjuvant LHRH+EMP therapy included the administration of 280 mg/day of LHRH and EMP for 6 months before RP. The outcome measure was BRFS. Results: The 5-year BRFS rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9% and 54.7%, respectively ( P < 0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Conclusions: Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP might reduce the risk of biochemical recurrence.

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Neoadjuvant therapy in high-risk prostate cancer

Indian Journal of Urology ◽

10.4103/iju.iju_115_20 ◽

2020 ◽

Vol 36 (4) ◽

pp. 251

Author(s):

Monish Aron ◽

AkbarN Ashrafi ◽

Wesley Yip

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Neoadjuvant Therapy ◽

High Risk Prostate Cancer ◽

Risk Prostate Cancer

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Pathologic response to neoadjuvant therapy of high risk prostate cancer

Cancer Urology ◽

10.17650/1726-9776-2020-16-3-80-89 ◽

2020 ◽

Vol 16 (3) ◽

pp. 80-89

Author(s):

M. V. Berkut ◽

A. S. Artemjeva ◽

S. S. Tolmachev ◽

S. A. Reva ◽

S. V. Petrov ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Neoadjuvant Therapy ◽

Pathologic Response ◽

Relapse Free Survival ◽

Free Survival ◽

Chemohormonal Therapy ◽

High Risk Prostate Cancer ◽

Risk Prostate Cancer ◽

Group B

Background. The role of pathological response, which develops as a result of systemic therapy for localized and locally advanced high risk prostate cancer, is not still fully understood. There are no clear indications for neoadjuvant therapy and no data on the relationship between neoadjuvant therapy and median of overall or progression free survival. According to increasing interest for neoadjuvant chemohormonal therapy followed by radical prostatectomy, we evaluated the features of pathological response and its effects on overall and progression free survival rates.Objective. Estimating residual disease and pathologic response to neoadjuvant therapy of high risk prostate cancer and its relationship with oncological results.Materials and methods. This was a prospective randomized study: patients with prostate cancer of high and very high-risk groups (prostate specific antigen levels >20 ng/ml and/or Gleason score ≥8 and/or clinical stage ≥T2c) were treated with neoadjuvant chemohormonal therapy followed by radical prostatectomy (n = 36). The neoadjuvant course included the intravenous administration of docetaxel once every 21 days (75 mg/m2 up to 6 cycles) and the antagonist of the gonadotropin releasing hormone degarelix according to the standard scheme (6subcutaneous injections every 28 days). The prostate tissue was evaluated for the residual disease, features of pathological response according to the ABC system. Additionally, the expression of IHC markers (p53, bcl-2, p16, Ki-67, androgen receptors, c-MYC, ERG, PTEN) was evaluated on postoperative material using tissue microarray.Results. A totally of 480 H&Epostoperative and 775 H&E biopsy slides were analyzed. Group A included 10 (32.3 %) cases, group B — 16 (51.6 %), and group C — 5 (16.1 %). The variance analysis revealed a significant difference in the frequency of more localized forms of prostate cancer in group B (43.7 %) (p = 0.028). During assessment we did not found any relationship ABC system assignment and preoperative prostate specific antigen level, the presence of a positive surgical margin, the pathological stage of diseases or regional lymph nodes involvement. However, the values of relapse-free survival vary sharply between groups: the highest median of relapse-free survival was found in group B — 23.02 ± 12.61 months, patients of groups A/C could not achieve the level of median relapse-free survival — 11.7 ± 6.43 and 16.19 ± 16.54 months respectively.Conclusion. The effectiveness of neoadjuvant chemohormonal therapy for high risk prostate cancer can be assessed by the features of pathologic response through ABC system which has demonstrated own versatility and reproducibility in presented material. Neoadjuvant therapy with docetaxel and degarelix can improve the treatment outcomes of prostate cancer patients at high and very high risk of disease progression. The data on changes in the prostate tissue can be helpful in predicting the duration of the effect after chemohormonal therapy with subsequent surgery.

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Oncologic outcomes of radical prostatectomy with neoadjuvant LHRH agonist/estramustine and radiotherapy with neoadjuvant hormonal therapy for high-risk prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.259 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 259-259

Author(s):

Takuya Koie ◽

Hayato Yamamoto ◽

Atsushi Imai ◽

Shingo Hatakeyama ◽

Takahiro Yoneyama ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Radical Prostatectomy ◽

Propensity Score ◽

Neoadjuvant Therapy ◽

Propensity Score Matching ◽

Oncologic Outcomes ◽

Treatment Modalities ◽

High Risk Prostate Cancer ◽

Risk Prostate Cancer

259 Background: To date, the different treatment modalities for high-risk prostate cancer (Pca) have not been compared in any sufficiently large-scale, prospective, randomized clinical trial. We used propensity-score matching analysis to compare the oncological outcomes of high-risk prostate cancer between patients treated with radical prostatectomy (RP) and those treated with radiation therapy (RT). Methods: We studied 216 patients who received neoadjuvant therapy followed by RP (RP cohort) and 81 patients who received neoadjuvant androgen-deprivation therapy (ADT) followed by RT (RT cohort). The RP cohort received a luteinizing hormone-releasing hormone agonist and estramustine phosphate (280 mg/day) for 6 months prior to RP. The RT cohort received ADT for at least 6 months prior to RT using a 3-dimensional conformal radiotherapy technique. The total radiation dose was 70–76 Gy administered at 2 Gy/fraction. Results: Propensity-score matching identified 78 matched pairs of patients. The 3-year overall survival (OS) rates were 98.3% and 92.1% in the RP and RT groups, respectively (P = 0.156). The 3-year biochemical recurrence-free survival rates were 86.4% and 89.4% in the RP and RT groups, respectively (P = 0.878). Conclusions: Our study findings may suggest almost identical cancer control of RP and RT with appropriate neoadjuvant therapy in high-risk Pca. Therefore, issues of health-related quality of life may have important impact on decision making of treatment in high-risk Pca.

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Comparison between robot-assisted radical prostatectomy and minimum incision endoscopic radical prostatectomy for high-risk prostate cancer following neoadjuvant therapy: A propensity score-matched analysis

Annals of Oncology ◽

10.1093/annonc/mdy434.003 ◽

2018 ◽

Vol 29 ◽

pp. ix68-ix69

Author(s):

A. Imai ◽

H. Yamamoto ◽

S. Hatakeyama ◽

T. Yoneyama ◽

Y. Hashimoto ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Radical Prostatectomy ◽

Propensity Score ◽

Neoadjuvant Therapy ◽

Robot Assisted ◽

High Risk Prostate Cancer ◽

Risk Prostate Cancer

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Interstitial fibrosis in radical prostatectomy specimen treated with neoadjuvant therapy and its relationship to biochemical outcome and castration-resistant status in high-risk prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.251 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 251-251

Author(s):

Yasuhiro Hashimoto ◽

Akiko Okamoto ◽

Hayato Yamamoto ◽

Atsushi Imai ◽

Shingo Hatakeyama ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Radical Prostatectomy ◽

Neoadjuvant Therapy ◽

Interstitial Fibrosis ◽

Lhrh Agonist ◽

Free Survival ◽

High Risk Prostate Cancer ◽

Castration Resistant ◽

Risk Prostate Cancer

251 Background: Interstitial fibrosis (IF) have been known to occur in radical prostatectomy specimens treated with hormonal therapy. We previously reported that neoadjuvant therapy for high-risk prostate cancer (Pca) with luteinizing hormone-releasing hormone (LHRH) agonist and low-dose estramustine phosphate (EMP) (LHRH + EMP) significantly improved biochemical recurrence (BCR) free survival. In this study, we quantified IF in radical prostatectomy specimens treated with neoadjuvant LHRH + EMP, and we examined whether degree of IF has impact on BCR free survival or subsequent castration-resistant status. Methods: High-risk Pca was defined by the D’Amico stratification system. A total of 103 patients with high-risk Pca were enrolled in this study from July 2005 to August 2010. The LHRH + EMP therapy included the administration of the LHRH agonist and 280 mg/day of EMP for six months before the radical prostatectomy. BCR was defined as the prostate-specific antigen (PSA) levels greater than 0.2 ng/mL after the prostatectomy. Castration-resistant prostate cancer (CRPC) is defined by PSA or radiographic progression in the castrate levels of testosterone (< 50 ng/dL). A quantitative analysis of IF was performed using computer-assisted imaging. Results: The average patient age was 67.2 (49 to 78), and the median initial PSA level was 18.8 ng/mL (4.2–95.6). All patients completed six months of LHRH + EMP neoadjuvant therapy with no delays in the radical prostatectomy. At a median follow-up period of 64.0 months, BCR occurred in 41 patients (39.8%) and CRPC occurred in nine patients (8.7%). The average IF rate was 0.43 (0.33–0.55). The five year BCR-free survival rates for the groups with IF rates less than 0.42 and greater than 0.42 were 74.7% and 50.0%, respectively. The log-rank test was significantly different between the two groups (p = 0.010). We could not identify CRPC in the patients with IF rates less than 0.42. Conclusions: Although the present study was small and preliminary, the IF rate may have a predictive potential for biochemical outcome and the occurrence of CRPC after neoadjuvant therapy for high-risk Pca. Further study is warranted to elucidate its clinical significance.

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