scholarly journals Hypoxia-Inducible Factor 2a Expression Is Positively Correlated With Gleason Score in Prostate Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382199001
Author(s):  
Dimitrios Pavlakis ◽  
Spyridon Kampantais ◽  
Konstantinos Gkagkalidis ◽  
Victoras Gourvas ◽  
Dimitrios Memmos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Locally Advanced ◽  
Hypoxia Inducible Factor ◽  
Immunohistochemical Expression ◽  
Locally Advanced Prostate Cancer ◽  
Grade Group ◽  
Main Factors ◽  
Hif Pathway ◽  
Lower Expression

Background: One of the main factors in response to hypoxia in the tumor microenvironment is the hypoxia-inducible factor (HIF) pathway. Although its role in other solid tumors, particularly renal cell carcinoma, has been sufficiently elucidated, it remains elusive in prostate cancer. The aim of the present study was to investigate the expression of main proteins involved in this pathway and determine the correlation of the results with clinicopathological outcomes of patients with prostate cancer. Methods: The immunohistochemical expression of HIF-1a, HIF-2a and their regulators, prolyl hydroxylase domain (PHD)1, PHD2 and PHD3 and factor inhibiting HIF (FIH), was assessed on a tissue microarray. This was constructed from radical prostatectomy specimens, involving both tumor and corresponding adjacent non-tumoral prostate tissues from 50 patients with localized or locally advanced prostate cancer. Results: In comparison with non-tumoral adjacent tissue, HIF-1a exhibited an equal or lower expression in 86% of the specimens (P = 0.017), while HIF-2a was overexpressed in 52% (P = 0.032) of the cases. HIF-1a protein expression was correlated with HIF-2a (P < 0.001), FIH (P = 0.004), PHD1 (P < 0.001), PHD2 (P < 0.001) and PHD3 (P = 0.035). HIF-2a expression was positively correlated with Gleason score (P = 0.017) and International Society of Urological Pathologists (ISUP) grade group (P = 0.022). Conclusions: The findings of the present study suggest a key role for HIF-2a in prostate cancer, as HIF-2a expression was found to be correlated with Gleason score and ISUP grade of the patients. However, further studies are required to validate these results and investigate the potential value of HIF-2a as a therapeutic target in prostate cancer.

scholarly journals Achieving PSA < 0.2 ng/ml before Radiation Therapy Is a Strong Predictor of Treatment Success in Patients with High-Risk Locally Advanced Prostate Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Akira Kazama ◽  
Toshihiro Saito ◽  
Keisuke Takeda ◽  
Kazuhiro Kobayashi ◽  
Toshiki Tanikawa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Treatment Outcome ◽  
High Risk ◽  
Gleason Score ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Locally Advanced Prostate Cancer ◽  
T Stage

Background. To predict long-term treatment outcome of radiation therapy (RT) plus androgen deprivation therapy (ADT) for high-risk locally advanced prostate cancer. Methods. In total, 204 patients with the National Comprehensive Cancer Network (NCCN) high risk locally advanced prostate cancer (PSA > 20 ng/ml, Gleason score ≧ 8, clinical T stage ≧ 3a) were treated with definitive RT with ADT. Median follow up period was 113 months (IQR: 95–128). Median neoadjuvant ADT and total ADT duration were 7 months (IQR: 6–10) and 27 months (IQR: 14–38), respectively. Results. PSA recurrence-free survival (PSA-RFS), cancer specific survival (CSS), and overall survival (OS) rates at 5 years were 84.1%, 98.5%, and 93.6%, respectively, and 67.9%, 91.2%, and 78.1%, respectively, at 10 years. Pre-RT PSA less than 0.2 ng/ml was associated with superior outcomes of PSA-RFS (HR = 0.42, 95% CI: 0.25–0.70, p=0.001), CSS (HR = 0.27, 95% CI: 0.09–0.82, p=0.013), and OS (HR = 0.48, 95% CI: 0.26–0.91, p=0.021). On multivariate analysis, age (≥70 y.o.) and pre-RT PSA (≥0.2 ng/ml) were factors predictive of poorer OS (p=0.032) , but iPSA, T stage, Gleason score, number of NCCN high-risk criteria, a combination with anti-androgen therapy and neoadjuvant ADT duration were not predictive of treatment outcome. Conclusion. In patient with high-risk prostate cancer, RT plus ADT achieved good oncologic outcomes. PSA < 0.2 ng/ml before radiation therapy is a strong independent predictor for long overall survival.

Osteopenia (OP) induced by 6 and 18 months androgen deprivation (AD)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5123-5123
Author(s):  
J. Ball
Keyword(s):  
Prostate Cancer ◽  
Bone Mineral ◽  
Gleason Score ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Androgen Deprivation ◽  
Locally Advanced Prostate Cancer ◽  
Optimal Duration ◽  
Financial Relationships

5123 Background: In a trial evaluating the optimal duration of AD in locally advanced prostate cancer (PC) we sought to determine whether 18 months of zoledronate (Zd) would reverse AD induced OP and reduce bony failure. Methods: In the four arm 2x2 TROG 03.04 (RADAR) trial, men with T2b,c-4 and T2a (Gleason score >6, PSA >10) N0 M0 PC (but without osteoporosis) were randomised to leuprotide (Lp) 22.5 mgs i.m. 3 monthly for 6 months starting 5 months prior to radiotherapy (RT) in Arm A, or the same treatment with Zd mgs i.v.i. 3 months for 18 months commencing on Day 1 (in Arms B and D), or with Lp 22.5 mg i.m. 3 monthly for 12 months after RT (in Arms C and D). Hip and spinal bone mineral densities (BMD) were measured before treatment (bt) and then at 2 and 4 years using DEXA and differences between trial arms were assessed by paired t tests. OP was defined by T- scores <-1. Results: Between October 2003 and January 2006, 930 men were randomized. 124 men with BMD measures bt and at 2 years are evaluable. Mean change (±SD) in BMD between 0 and 2 years was -0.005 ±0.05 (p=0.57) in Arm A, 0.085 ±0.06 (p=<0.001) in Arm B, 0.054 ±0.07 (p=<0.001) in Arm C, and 0.065 ±0.05 (p=<0.001) in Arm D. 98 men had normal BMD bt. Of these 6 of 51 in Arms A, C (no Zd) have developed OP at 2 years while none of 47 in Arms B, D (+Zd) have as yet. Conclusions: At 2 years OP caused by 6 months AD is minimal, but remains significant after 18 months AD. This is reversed by 18 months Zd, but further follow up will determine whether this degree of OP resolves with time or causes fractures. No significant financial relationships to disclose.

Ten-Year Follow-Up of Radiation Therapy Oncology Group Protocol 92-02: A Phase III Trial of the Duration of Elective Androgen Deprivation in Locally Advanced Prostate Cancer

2008 ◽  
Vol 26 (15) ◽  
pp. 2497-2504 ◽  
Author(s):  
Eric M. Horwitz ◽  
Kyounghwa Bae ◽  
Gerald E. Hanks ◽  
Arthur Porter ◽  
David J. Grignon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Gleason Score ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Androgen Deprivation ◽  
Locally Advanced Prostate Cancer ◽  
End Points

PurposeTo determine whether adding 2 years of androgen-deprivation therapy (ADT) improved outcome for patients electively treated with ADT before and during radiation therapy (RT).Patients and MethodsProstate cancer patients with T2c-T4 prostate cancer with no extra pelvic lymph node involvement and prostate-specific antigen (PSA) less than 150 ng/mL were included. All patients received 4 months of goserelin and flutamide before and during RT. They were randomized to no further ADT (short-term ADT [STAD] + RT) or 24 months of goserelin (long-term ADT [LTAD] + RT). A total of 1,554 patients were entered. RT was 45 Gy to the pelvic nodes and 65 to 70 Gy to the prostate. Median follow-up of all survival patients is 11.31 and 11.27 years for the two arms.ResultsAt 10 years, the LTAD + RT group showed significant improvement over the STAD + RT group for all end points except overall survival: disease-free survival (13.2% v 22.5%; P < .0001), disease-specific survival (83.9% v 88.7%; P = .0042), local progression (22.2% v 12.3%; P < .0001), distant metastasis (22.8% v 14.8%; P < .0001), biochemical failure (68.1% v 51.9%; P ≤ .0001), and overall survival (51.6% v 53.9%, P = .36). One subgroup analyzed consisted of all cancers with a Gleason score of 8 to 10 cancers. An overall survival difference was observed (31.9% v 45.1%; P = .0061), as well as in all other end points herein.ConclusionLTAD as delivered in this study for the treatment of locally advanced prostate cancer is superior to STAD for all end points except survival. A survival advantage for LTAD + RT in the treatment of locally advanced tumors with a Gleason score of 8 to 10 suggests that this should be the standard of treatment for these high-risk patients.

Neoadjuvant Chemotherapy and Hormonal Therapy Followed by Radical Prostatectomy: Feasibility and Preliminary Results

2000 ◽  
Vol 18 (5) ◽  
pp. 1050-1050 ◽  
Author(s):  
Curtis A. Pettaway ◽  
Louis L. Pisters ◽  
Patricia Troncoso ◽  
Joel Slaton ◽  
Laury Finn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Neoadjuvant Chemotherapy ◽  
Gleason Score ◽  
Hormonal Therapy ◽  
Advanced Prostate Cancer ◽  
Intraoperative Complications ◽  
Locally Advanced ◽  
Locally Advanced Prostate Cancer ◽  
Androgen Ablation

PURPOSE: We assessed the feasibility and efficacy of integrating chemotherapy and androgen ablation with radical prostatectomy in patients with locally advanced prostate cancer. The neoadjuvant approach was adopted because it allows an in situ assessment of antitumoral activity.PATIENTS AND METHODS: Thirty-three patients were enrolled who met the clinical criteria of stage T1–2, Gleason score of ≥ 8 or T2b-T2c, Gleason score of 7 and prostate-specific antigen (PSA) level greater than 10 ng/mL (n = 15), or clinical stage T3 (n = 18). Therapy consisted of 12 weeks of ketoconazole and doxorubicin alternating with vinblastine, estramustine, and androgen ablation followed by prostatectomy. The ability of neoadjuvant chemotherapy and hormonal therapy to induce a 20% rate of pT0 in the prostatectomy specimen as well as surgical feasibility were assessed.RESULTS: Chemotherapy complications were comparable to those reported with this regimen previously. No major intraoperative complications occurred. Postoperative complications occurred in 10 (33%) of 30 patients. One patient died at home after discharge (postoperative day 17; no autopsy was performed). Ten (33%) of the 30 patients had organ-confined disease, and 20 (70%) of 30 had extraprostatic extension; 11 (37%) of the 30 had positive lymph nodes. Only five (17%) of 30 exhibited positive surgical margins. All patients achieved an undetectable PSA level postoperatively, and 20 of the surviving 29 patients remain without disease recurrence with a median follow-up of 13 months (range, 9 to 18 months).CONCLUSION: Chemotherapy and androgen ablation followed by radical prostatectomy was feasible in patients with locally advanced prostate cancer. Although the goal of achieving a 20% rate for pT0 status was not achieved, we believe this type of integrated therapeutic strategy should be investigated further for its ability to alter the course of regionally advanced prostate cancer.

Role of Radical Retropubic Prostatectomy in Patients with Locally Advanced Prostate Cancer: The Influence of Gleason Score 8–10

2003 ◽  
Vol 70 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Alessandro Sciarra ◽  
Vincenzo Gentile ◽  
Giuseppe Voria ◽  
Gianna Mariotti ◽  
Fulvia Seccareccia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Radical Retropubic Prostatectomy ◽  
Locally Advanced Prostate Cancer ◽  
Retropubic Prostatectomy

Matched-Pair Analysis of Conformal High–Dose-Rate Brachytherapy Boost Versus External-Beam Radiation Therapy Alone for Locally Advanced Prostate Cancer

2000 ◽  
Vol 18 (15) ◽  
pp. 2869-2880 ◽  
Author(s):  
Larry L. Kestin ◽  
Alvaro A. Martinez ◽  
Jannifer S. Stromberg ◽  
Gregory K. Edmundson ◽  
Gary S. Gustafson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
High Dose Rate ◽  
External Beam Radiation ◽  
Matched Pair ◽  
High Dose ◽  
Locally Advanced Prostate Cancer ◽  
Beam Radiation

PURPOSE: We performed a matched-pair analysis to compare our institution’s experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high–dose-rate (HDR) brachytherapy boosts (EBRT + HDR). MATERIALS AND METHODS: From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of ≥ 10.0 ng/mL, Gleason score ≥ 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy) was supplemented with three (1991 through 1995) or two (1995 through 1998) ultrasound-guided transperineal interstitial iridium-192 HDR implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P < .001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P < .001). CONCLUSION: Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.

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