Hypofractionated, dose escalation radiotherapy for high-risk prostate cancer: The primary endpoint of a group led phase III trial. (PCS5).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 123-123 ◽  
Author(s):  
Tamim Niazi ◽  
Abdenour Nabid ◽  
Redouane Bettahar ◽  
Linda S. Vincent ◽  
Andre-Guy Martin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Lymph Nodes ◽  
Primary Endpoint ◽  
Dose Escalation ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Pelvic Lymph Nodes ◽  
Androgen Suppression ◽  
Grade 3

123 Background: The low α\β ratio of prostate cancer (PCa), 1.5-2, suggests high radiation-fraction sensitivity and predicts a therapeutic advantage of hypofractionated radiation treatment (HFRT). Most available data of moderate HFRT have focused on low, intermediate and/or mixed risk groups. We therefore conducted the first randomized trial of moderately HFRT in high-risk PCa patients and present the primary safety analysis of side effects at 2 years. Methods: We conducted a Canadian multi-centric phase III trial of conventional fractionated radiation therapy (CFRT) vs. intensity-modulated HFRT in men with high-risk PCa as per NCCN definition. From February 2012 to March 2015, 329 patients were randomized in a 1:1 ratio to receive either CFRT or HFRT. All patients received neo-adjuvant, concurrent and adjuvant androgen suppression, with a median duration of 24 months. CFRT consisted of 76 Gy in 2 Gy per fraction to the prostate where 46 Gy was delivered to the pelvic lymph nodes. HFRT consisted of concomitant dose escalation of 68 Gy in 2.72 Gy per fraction to the prostate and 45 Gy, in 1.8Gy per fraction to the pelvic lymph nodes. The primary endpoint was to compare the toxicities at 6 months and at 24 months using the CTCAE v.4. Results: Of the329 patients, 164 were randomized to HFRT and 165 to CFRT. The minimum, median and maximum follow-up were 24, 40 and 60 months respectively. At 24 months, 12 patients in the CFRT arm and 15 patients in the HFRT arm had grade 2 or worse gastrointestinal (GI)-related adverse events (HR:1.32 [0.62.2.83] 95% CI; P=NS). Similarly, 11 patients in the CFRT arm and 3 patients in HFRT arm had grade 2 or higher genitourinary (GU) toxicities (HR:0.26 [0.07-0.94] 95% CI; P=0.037). In the HFRT arm, there were 3 grade 3 GI and one grade 3 GU related toxicities. In the CFRT arm there were 3 grade 3 GU and no grade 3 GI related toxicities. There were no grade 4 toxicities in either arm. Conclusions: This is the first hypofractionated dose escalated radiotherapy study in high-risk PCa patients treated with contemporary radiation and androgen suppression. Our results indicate that moderate HFRT to high risk PCa patients is equally well tolerated as CFRT at 2 years. Clinical trial information: NCT01444820.

scholarly journals Proton Therapy of Prostate and Pelvic Lymph Nodes for High Risk Prostate Cancer: Acute Toxicity

2021 ◽  
Vol 8 (2) ◽  
pp. 41-50
Author(s):  
Richard Choo ◽  
David W. Hillman ◽  
Thomas Daniels ◽  
Carlos Vargas ◽  
Jean Claude Rwigema ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Acute Toxicity ◽  
Lymph Nodes ◽  
Seminal Vesicles ◽  
Pelvic Lymph Nodes ◽  
Gu Toxicity ◽  
Risk Prostate Cancer ◽  
Gi Toxicity ◽  
Grade 3

Abstract Purpose To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities of intensity-modulated proton therapy (IMPT) targeting the prostate/seminal vesicles and pelvic lymph nodes for prostate cancer. Materials and Methods A prospective study (ClinicalTrials.gov: NCT02874014), evaluating moderately hypofractionated IMPT for high-risk or unfavorable intermediate-risk prostate cancer, accrued a target sample size of 56 patients. The prostate/seminal vesicles and pelvic lymph nodes were treated simultaneously with 6750 and 4500 centigray radiobiologic equivalent (cGyRBE), respectively, in 25 daily fractions. All received androgen-deprivation therapy. Acute GI and GU toxicities were prospectively assessed from 7 GI and 9 GU categories of the Common Terminology Criteria for Adverse Events (version 4), at baseline, weekly during radiotherapy, and 3-month after radiotherapy. Fisher exact tests were used for comparisons of categorical data. Results Median age was 75 years. Median follow-up was 25 months. Fifty-five patients were available for acute toxicity assessment. Sixty-two percent and 2%, respectively, experienced acute grade 1 and 2 GI toxicity. Grade 2 GI toxicity was proctitis. Sixty-five percent and 35%, respectively, had acute grade 1 and 2 GU toxicity. The 3 most frequent grade 2 GU toxicities were urinary frequency, urgency, and obstructive symptoms. None had acute grade ≥ 3 GI or GU toxicity. The presence of baseline GI and GU symptoms was associated with a greater likelihood of experiencing acute GI and GU toxicity, respectively. Of 45 patients with baseline GU symptoms, 44% experienced acute grade 2 GU toxicity, compared with only 10% among 10 with no baseline GU symptoms (P = 0.07). Although acute grade 1 and 2 GI and GU toxicities were common during radiotherapy, most resolved at 3 months after radiotherapy. Conclusion A moderately hypofractionated IMPT targeting the prostate/seminal vesicles and regional pelvic lymph nodes was well tolerated with no acute grade ≥ 3 GI or GU toxicity. Patients with baseline GU symptoms had a higher rate of acute grade 2 GU toxicity.

Short Androgen Suppression and Radiation Dose Escalation for Intermediate- and High-Risk Localized Prostate Cancer: Results of EORTC Trial 22991

2016 ◽  
Vol 34 (15) ◽  
pp. 1748-1756 ◽  
Author(s):  
Michel Bolla ◽  
Philippe Maingon ◽  
Christian Carrie ◽  
Salvador Villa ◽  
Petros Kitsios ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Lymph Nodes ◽  
Clinical Evidence ◽  
Progression Free Survival ◽  
Metastatic Spread ◽  
Localized Prostate Cancer ◽  
Free Survival ◽  
Pelvic Lymph Nodes ◽  
Androgen Suppression

Purpose Up to 30% of patients who undergo radiation for intermediate- or high-risk localized prostate cancer relapse biochemically within 5 years. We assessed if biochemical disease-free survival (DFS) is improved by adding 6 months of androgen suppression (AS; two injections of every-3-months depot of luteinizing hormone–releasing hormone agonist) to primary radiotherapy (RT) for intermediate- or high-risk localized prostate cancer. Patients and Methods A total of 819 patients staged: (1) cT1b-c, with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≥ 7, or (2) cT2a (International Union Against Cancer TNM 1997), with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread, with PSA ≤ 50 ng/mL, were centrally randomized 1:1 to either RT or RT plus AS started on day 1 of RT. Centers opted for one dose (70, 74, or 78 Gy). Biochemical DFS, the primary end point, was defined from entry until PSA relapse (Phoenix criteria) and clinical relapse by imaging or death of any cause. The trial had 80% power to detect hazard ratio (HR), 0.714 by intent-to-treat analysis stratified by dose of RT at the two-sided α = 5%. Results The median patient age was 70 years. Among patients, 74.8% were intermediate risk and 24.8% were high risk. In the RT arm, 407 of 409 patients received RT; in the RT plus AS arm, 403 patients received RT plus AS and three patients received RT only. At 7.2 years median follow-up, RT plus AS significantly improved biochemical DFS (HR, 0.52; 95% CI, 0.41 to 0.66; P < .001, with 319 events), as well as clinical progression-free survival (205 events, HR, 0.63; 95% CI, 0.48 to 0.84; P = .001). In exploratory analysis, no statistically significant interaction between treatment effect and dose of RT could be evidenced (heterogeneity P = .79 and P = .66, for biochemical DFS and progression-free survival, respectively). Overall survival data are not mature yet. Conclusion Six months of concomitant and adjuvant AS improves biochemical and clinical DFS of intermediate- and high-risk cT1b-c to cT2a (with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread) prostatic carcinoma, treated by radiation.

scholarly journals Volumetric Modulated Arc Therapy of the Pelvic Lymph Nodes to the Aortic Bifurcation in Higher Risk Prostate Cancer: Early Toxicity Outcomes

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Gina Hesselberg ◽  
Gerald Fogarty ◽  
Lauren Haydu ◽  
Nicole Dougheney ◽  
Phillip Stricker
Keyword(s):  
Prostate Cancer ◽  
Lymph Nodes ◽  
Radiation Therapy Oncology Group ◽  
Volumetric Modulated Arc Therapy ◽  
Toxicity Profile ◽  
Aortic Bifurcation ◽  
Pelvic Lymph Nodes ◽  
Arc Therapy ◽  
Grade 3 ◽  
Early Toxicity

Background. Treatment of pelvic lymph nodes (PLNs) in higher risk prostate carcinoma is controversial. The primary focus of the study was to evaluate the early toxicity profile for this cohort of patients treated with Volumetric Modulated Arc Therapy (VMAT).Methods. Patient, tumour, and treatment characteristics of those who received VMAT from May 2010 to December 2012 were analysed. A simplified contouring process of the PLNs to the aortic bifurcation was developed based on consensus guidelines. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were documented according to the Radiation Therapy Oncology Group (RTOG) Version 2 Guidelines. Successive Prostate Specific Antigen (PSA) values after treatment were measured on average 3 months apart.Results. 113 patients were treated between May 2010 to December 2012 with a median follow-up of 14 months. No patients experienced acute grade 3 or 4 GU and GI toxicity. Only 1 patient experienced a late grade 3 GU complication. No late grade 4 GU or GI events have yet occurred.Conclusions. This study reviews the first Australian experience of VMAT in the treatment of pelvic lymph nodes in prostate cancer, specifically to the level of the aortic bifurcation. It demonstrates a favorable acute toxicity profile whilst treating large PLN volumes with optimal dose coverage.

Molecular Load of Pathologically Occult Metastases in Pelvic Lymph Nodes Is an Independent Prognostic Marker of Biochemical Failure After Localized Prostate Cancer Treatment

2006 ◽  
Vol 24 (19) ◽  
pp. 3081-3088 ◽  
Author(s):  
Anna C. Ferrari ◽  
Nelson N. Stone ◽  
Ralf Kurek ◽  
Elizabeth Mulligan ◽  
Roy McGregor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Lymph Nodes ◽  
Prognostic Marker ◽  
Risk Group ◽  
High Risk Group ◽  
Biochemical Failure ◽  
Localized Prostate Cancer ◽  
Pelvic Lymph Nodes ◽  
Independent Prognostic Marker

Purpose Thirty percent of patients treated with curative intent for localized prostate cancer (PC) experience biochemical recurrence (BCR) with rising serum prostate-specific antigen (sPSA), and of these, approximately 50% succumb to progressive disease. More discriminatory staging procedures are needed to identify occult micrometastases that spawn BCR. Patients and Methods PSA mRNA copies in pathologically normal pelvic lymph nodes (N0-PLN) from 341 localized PC patients were quantified by real-time reverse-transcriptase polymerase chain reaction. Based on comparisons with normal lymph nodes and PLN with metastases and on normalization to 5 × 106 glyceraldehyde-3′-phosphate dehydrogenase mRNA copies, normalized PSA copies (PSA-N) and a threshold of PSA-N 100 or more were selected for continuous and categorical multivariate analyses of biochemical failure-free survival (BFFS) compared with established risk factors. Results At median follow-up of 4 years, the BFFS of patients with PSA-N 100 or more versus PSA-N less than 100 was 55% and 77% (P = .0002), respectively. The effect was greatest for sPSA greater than 20 ng/mL, 25% versus 60% (P = .014), Gleason score 8 or higher, 21% versus 66% (P = .0002), stage T3c, 18% versus 64% (P = .001), and high-risk group (50% v 72%; P = .05). By continuous analysis PSA-N was an independent prognostic marker for BCR (P = .049) with a hazard ratio of 1.25 (95% CI, 1.001 to 1.57). By categorical analysis, PSA-N 100 or more was an independent variable (P = .021) with a relative risk of 1.98 (95% CI, 1.11 to 3.55) for BCR compared with PSA-N less than 100. Conclusion PSA-N 100 or more is a new, independent molecular staging criterion for localized PC that identifies high-risk group patients with clinically relevant occult micrometastases in N0-PLN, who may benefit from additional therapy to prevent BCR.

A study of ERG, PTEN, and ki-67 in a phase III trial assessing docetaxel and estramustine in high-risk localized prostate cancer (GETUG 12).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 5063-5063 ◽  
Author(s):  
Shanna Rajpar ◽  
Philippe Vielh ◽  
Agnes Laplanche ◽  
Francois Lesaunier ◽  
Remy Delva ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Ki 67 ◽  
Phase Iii Trial

Docetaxel-estramustine in localized high-risk prostate cancer: Results of the French Genitourinary Tumor Group GETUG 12 phase III trial.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 5005-5005 ◽  
Author(s):  
Karim Fizazi ◽  
Agnes Laplanche ◽  
Francois Lesaunier ◽  
Remy Delva ◽  
Gwenaelle Gravis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
High Risk Prostate Cancer ◽  
Tumor Group ◽  
Risk Prostate Cancer
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