Adjuvant androgen deprivation (ADT) versus mitoxantrone plus prednisone (MP) plus ADT in high-risk prostate cancer (PCa) patients following radical prostatectomy: A phase III intergroup trial (SWOG S9921) NCT00004124.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
L. Michael Glode ◽  
Catherine M. Tangen ◽  
Maha Hussain ◽  
Gregory P. Swanson ◽  
David Peter Wood ◽  
...  
Keyword(s):  
High Risk ◽  
Radical Prostatectomy ◽  
Positive Margin ◽  
Phase Iii ◽  
Adjuvant Radiation ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
To Receive ◽  
Clinical Trial Information

2 Background: High risk localized Pca patients are more likely to relapse and suffer morbidity/mortality from metastatic disease after prostatectomy. Adjuvant ADT can reduce this risk. We hypothesized that MP in addition to two years of ADT could further reduce mortality from PCa. Methods: Participants with clinically localized (T1-T3, N0, M0) PCa received radical prostatectomy. Eligibility required ≥ 1 high risk criteria defined as Gleason sum ≥8; pT3b or pT4 or N1; Gleason 7 with positive margin; any one of these preoperative findings: PSA>15ng/ml, biopsy Gleason >7, biopsy Gleason >6 with PSA>10. ADT arm consisted of bicalutamide and goserelin for 2 years. ADT+MP arm received ADT plus 6 cycles of M 12mg/m2+ P 5mg BID. Primary endpoint was survival (OS). Median OS was anticipated to be 10 years in ADT arm requiring 680 patients/arm to detect a hazard ratio of 1.30 with 92% power and one-sided α=0.05. Results: S9921 enrolled patients from 10/99 to 1/07 when the DSMC recommended stopping due to increased incidence of leukemia in the ADT+MP arm. Of 983 patients randomized, 22 ineligible. 481 eligible on ADT and 480 on ADT+MP. Patients were stratified by stage (≤pT2, ≥pT3, N0 or N+), Gleason score, and intent to receive adjuvant radiation (RT) (Y/N). Median age was 60 years, 84% were white, presurgical PSA was 7.6 ng/ml, 16% had positive nodes, 26% intended to receive RT, 63% had positive margins. 11 ADT and 20 ADT+ MP received no protocol treatment. Median follow-up is 11.2 years. Conclusions: Survival was greater than anticipated in both arms. MP increases the risk of leukemia. There is no evidence that MP improves PCa specific survival when added to 2 years of adjuvant ADT. Clinical trial information: NCT00004124. [Table: see text]

scholarly journals Phase III Intergroup Trial of Adjuvant Androgen Deprivation With or Without Mitoxantrone Plus Prednisone in Patients With High-Risk Prostate Cancer After Radical Prostatectomy: SWOG S9921

2018 ◽  
Vol 36 (15) ◽  
pp. 1498-1504 ◽  
Author(s):  
Maha Hussain ◽  
Catherine M. Tangen ◽  
Ian M. Thompson ◽  
Gregory P. Swanson ◽  
David P. Wood ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Adjuvant Radiation ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

Purpose Patients with high-risk prostate cancer after radical prostatectomy are at risk for death. Adjuvant androgen-deprivation therapy (ADT) may reduce this risk. We hypothesized that the addition of mitoxantrone and prednisone (MP) to adjuvant ADT could reduce mortality compared with adjuvant ADT alone. Methods Eligible patients had cT1-3N0 prostate cancer with one or more high-risk factors after radical prostatectomy (Gleason score [GS] ≥ 8; pT3b, pT4, or pN+ disease; GS 7 and positive margins; or preoperative prostate-specific antigen [PSA] > 15 ng/mL, biopsy GS score > 7, or PSA > 10 ng/mL plus biopsy GS > 6. Patients with PSA ≤ 0.2 ng/mL after radical prostatectomy were stratified by pT/N stage, GS, and adjuvant radiation plan and randomly assigned to ADT (bicalutamide and goserelin for 2 years) or ADT plus six cycles of MP. The primary end point was overall survival (OS). Median OS was projected to be 10 years in the ADT arm, requiring 680 patients per arm to detect a hazard ratio of 1.30 with 92% power and one-sided α = .05. Results Nine hundred sixty-one eligible intent-to-treat patients were randomly assigned to ADT or ADT + MP from October 1999 to January 2007, when the Data Safety Monitoring Committee recommended stopping accrual as a result of higher leukemia incidence with ADT + MP. Median follow-up was 11.2 years. The 10-year OS estimates were 87% with ADT (expected 50%) and 86% with ADT + MP (hazard ratio, 1.06; 95% CI, 0.79 to 1.43). The 10-year estimate for disease-free survival was 72% for both arms. Prostate cancer was the cause of death in 18% of patients in the ADT arm and 22% in the ADT + MP arm. More patients in the MP arm died of other cancers (36% v 18% in ADT alone arm). Conclusion MP did not improve OS and increased deaths from other malignancies. The DFS and 10-year OS in these patients treated with 2 years of ADT were encouraging compared with historical estimates, although a definitive conclusion regarding value of ADT may not be made without a nontreatment control arm.

Extended versus limited pelvic lymphadenectomy during radical prostatectomy for intermediate- and high-risk prostate cancer: Early outcomes from a randomized controlled phase III study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5018-5018 ◽  
Author(s):  
Jean Felipe Prodocimo Lestingi ◽  
Giuliano Guglielmetti ◽  
Jose Pontes Jr ◽  
Anuar Ibrahim Mitre ◽  
Alvaro Sarkis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Phase Iii ◽  
Transfusion Rate ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

5018 Background: The role of extended pelvic lymph node dissection (ePLND) in treating prostate cancer (PCa) patients remains controversial, mainly by the lack of RCTs. Methods: Patients with D'Amico intermediate or high risk PCa, absence of bone metastasis and no previous treatment were prospectively computer randomised to undergo extended or limited PLND (1:1) during radical prostatectomy. Limited PLND (lPLND) included the obturator chain bilaterally; ePLND involved bilaterally chains: obturator, external-, internal-, common-iliac and pre-sacral. Surgical specimens and each chain were analyzed separately, according to College of American Pathologists. All patients signed a free and informed consent and local ethics committee approved the study. The primary endpoint was biochemical recurrence-free survival, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01812902. Results: Since May 2012 until August 2016, 291 patients were randomly assigned, 145 to ePLND and 146 to lPLND. Preoperative data were comparable between groups. Median follow-up was 35.2 months. EPLND increased significantly operative time (54 minutes), estimated blood loss (100 mL), length of hospital stays (1 day) [p≤0.001], transfusion rate [p = 0.05] and postoperative complications according to Clavien scale [p = 0.03]. There was no difference in Pathologic Gleason grade, T stage or positive surgical margin. On ePLND and lPLND groups, 59.3% and 61.7% were staged ≥ pT3a, respectively. EPLND and lPLND yielded median (mean) 17 (19.8) and 3 (4.1) nodes, respectively (p < 0.001). EPLND showed 6.3 times more lymph node metastases (p < 0.001) and only it was able to show positive nodes in intermediate risk. There were no difference in biochemical recurrence (PSA ≥ 0.2 ng/mL) using Kaplan-Meyer method (p = 0.4), Radiotherapy, Androgen Deprivation Therapy, bone metastases or death. Conclusions: Extended lymphadenectomy in intermediate- and high-risk prostate cancer patients is associated with better tumor staging, increased morbidity and no oncological benefits in this initial short follow-up time. Clinical trial information: NCT01812902.

Adjuvant androgen deprivation (AD) +/- mitoxantrone + prednisone (MP) in patients with high-risk prostate cancer (PC) post radical prostatectomy (RP): Phase III intergroup trial S9921.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5019-5019
Author(s):  
Maha Hussain ◽  
Catherine M. Tangen ◽  
Ian Murchie Thompson ◽  
Gregory P. Swanson ◽  
David Peter Wood ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Positive Margin ◽  
Phase Iii ◽  
Adjuvant Radiation ◽  
High Risk Factors ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Risk Definition ◽  
Systemic Relapse

5019 Background: Patients (pts) with high-risk PC post RP are at risk of systemic relapse with related morbidity/mortality. Adjuvant AD can reduce this risk. In 1999, based on available data, we hypothesized that adjuvant MP + 2 years (ys) of AD can further reduce mortality. Methods: Eligible pts had cT1-T3, N0 PC with post RP > = 1 high risk factors defined as Gleason sum (GS) ≥ 8, pT3b, pT4, pN+, GS 7 + positive margin or any of these preoperative findings (in pts with neoadjuvant AD): preoperative PSA of > 15 ng/ml, bx GS score > 7, or PSA of > 10 ng/ml + bx GS > 6. Pts had to have post RP PSA = < 0.2 ng/ml, were stratified by T, N, GS, and adjuvant radiation plan and randomized: Arm 1 AD (bicalutamide + goserelin for 2 ys) or Arm 2 AD + 6 cycles m 12 mg/m2 + P 5mg BID. Primary endpoint: overall survival (OS). Median OS was estimated to be 10 ys in AD arm requiring 680 pts/arm to detect a hazard ratio (HR) of 1.30 with 92% power and one-sided α = 0.05. Results: 983 pts (961 eligible intent to treat) with median age 60 ys and median PSA 7.6 ng/ml were randomized to AD or AD + MP from 10/99 -1/07 when the DSMC recommended stopping accrual due to higher leukemia rate in Arm 2. 16% had N1 (Group “Gr” 1), 61% GS ≥8 or pT3b (Gr 2),23% other risk factors (Gr 3). Median time to testosterone recovery was 9.5 months. Median follow-up (f/u) 11.2 ys. Conclusions: OS was higher than anticipated in both arms; MP did not improve OS and increased other malignancy risk. These data illustrate that systemic therapy benefit cannot be extrapolated from different disease stages and the importance of adequate f/u in adjuvant PCa trials. The remarkable DFS and 10 y OS, irrespective of risk extent, may be result of risk definition, and/or 2 ys AD. Pending definitive data 2 ys adjuvant AD for high-risk PCa post RP is a reasonable option to consider. Clinical trial information: NCT00004124. [Table: see text]

scholarly journals Observation with or without late radiotherapy is equivalent to early radiotherapy in high-risk prostate cancer after radical prostatectomy: A SEER-Medicare analysis on trends, survival outcomes and complications

2019 ◽  
Author(s):  
Young Suk Suk Kwon ◽  
Wei Wang ◽  
Arnav Srivast ◽  
Thomas L Jang ◽  
Singer A Eric ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Cox Regression ◽  
Survival Outcomes ◽  
Study Cohort ◽  
High Risk Prostate Cancer ◽  
Pathologic Features ◽  
Risk Prostate Cancer

Abstract Introduction: While early radiotherapy (eRT) after radical prostatectomy (RP) has shown to improve oncologic outcomes in patients with high-risk prostate cancer (PCa) in a recent clinical trial, controversy remains regarding its benefit. We aimed to illustrate national trends of post-RP radiotherapy and compare outcomes and toxicities in patients receiving eRT vs. observation with or without late radiotherapy (lRT). Methods: Utilizing the Surveillance, Epidemiology and End Results (SEER)-Medicare data from 2001 to 2011, we identified 7557 patients with high-risk pathologic features after RP (≥ pT3N0 and/or positive surgical margins). Our study cohort was consisted of patients receiving RT within 6 months of surgery (eRT), those receiving RT after 6 months (IRT), and those never receiving RT (observation). Another subcohort, delayed RT (dRT), encompassed both IRT and observation. Trends of post-RP radiotherapy were compared using the Cochran-Armitage trend test. Cox regression models identified factors predictive of worse survival outcomes. Kaplan-Meier analyses compared the eRT and the dRT groups. Results: Among those with pathologically confirmed high-risk PCa after RP, 12.7% (n=959), 13.2% (n=1710), and 74.1% (n=4888) underwent eRT, lRT, and observation without RT, respectively. Of these strategies, the proportion of men on observation without RT increased significantly over time (p=0.004). Multivariable Cox regression model demonstrated similar outcomes between the eRT and the dRT groups. At a median follow up of 5.9 years, five-year overall and cancer-specific survival outcomes were more favorable in the dRT group, when compared to the eRT group. Radiation related toxicities, including urinary incontinence, erectile dysfunction, and urethral stricture, were higher in the eRT group when compared to the lRT group. Conclusions: Our results suggest that a blanket adoption of the eRT in high-risk PCa based on clinical trials with limited follow up may result in overtreatment of a significant number of men and expose them to unnecessary radiation toxicity.

A randomized phase III trial between adjuvant docetaxel and surveillance after radical prostatectomy for high risk prostate cancer: Results of SPCG12.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5001-5001 ◽  
Author(s):  
Goran Ahlgren ◽  
Per Flodgren ◽  
Teuvo L. J. Tammela ◽  
Pirkko Kellokumpu-Lehtinen ◽  
Michael Borre ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

A randomized phase III trial between adjuvant docetaxel and surveillance after radical radiotherapy (RT) for intermediate and high-risk prostate cancer (PC): Quality-of-life results (QoL) in SPCG-13 trial.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 313-313
Author(s):  
Pirkko-Liisa Kellokumpu-Lehtinen ◽  
Marie Hjälm-Eriksson ◽  
Camilla Thellenberg-Karlsson ◽  
Lennart Astrom ◽  
Lars Franzen ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Phase Iii ◽  
High Risk Prostate Cancer ◽  
Psa Relapse ◽  
Anova Model ◽  
Docetaxel Treatment ◽  
Risk Prostate Cancer ◽  
To Receive

313 Background: Six docetaxel cycles did not improve PSA relapse free survival as an adjuvant treatment after radical RT (Kellokumpu-Lehtinen EURURO-8532). Here we report SPCG-13 trials QoL results. Methods: A total of 376 PC patients (T2 with Gleason score (GS) 4+3, PSA>10; T2, GS 8-10 any PSA; or any T3) were randomised to receive either 6 cycles of docetaxel 75mg/m2 every 3 weeks (Arm A, n=188) or surveillance (Arm B, n=188) after radical RT NTC006653848. Neoadjuvant/adjuvant ADT was mandatory. Primary end-point was a rising PSA > 2 ng/ml above the nadir. Patients were followed for 5 years with PSA every 3 months for two years and thereafter every 6 month. FACT-P QoL questionnaires were used at baseline, during and after docetaxel treatment and in the follow-ups (at 1 year, 2 years and 4 years after treatment) in both groups, and analysed using analysis of variance (ANOVA) models. Results: Median follow-up was 59.4 months (range 1 to 111 months). 147 (78.2%) patients completed all six cycles in arm A. Mean age was 66.2 years in Arm A and 66.4 years in Arm B. The total QoL scores at baseline did not differ between the Arms (mean 119.0, SD±18.9, n=177 vs 118.2, SD±18.1, n=180). In Arm A the total score declined to 116.3 (SD+15.2), at 24 weeks and was 118.5 (SD±21.3) after chemotherapy. In Arm B at 24 weeks the QoL score had increased to 123.3 (SD±19.2) and was significantly higher than in Arm A (estimated difference of 8.2 with p<0.0001, ANOVA model adjusted for baseline). However, in the first follow-up (1 year) the QoL score was same in both Arms (123.7 vs 123.6, respectively, p=0.344, ANOVA model adjusted for baseline) and remained at the same level during further follow-ups. The decline in QoL scores during the docetaxel treatment were seen only in two sub-scores; functional and physical. Conclusions: Adjuvant docetaxel did decrease the QoL of patients during the treatment. However, in the later follow-ups it increased to the same level as those patients without docetaxel treatment. These results further support our conclusions of showing no benefit from docetaxel as adjuvant treatment in this patient group after radical curative treatment. Clinical trial information: RT NTC006653848.

Long-term follow-up of a neoadjuvant chemohormonal taxane-based phase II trial before radical prostatectomy in patients with non-metastatic high-risk prostate cancer

2007 ◽  
Vol 100 (2) ◽  
pp. 274-280 ◽  
Author(s):  
Tomaso Prayer-Galetti ◽  
Emilio Sacco ◽  
Francesco Pagano ◽  
Marina Gardiman ◽  
Antonio Cisternino ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Long Term Follow Up

1488 TESTOSTERONE REPLACEMENT THERAPY IN PATIENTS WITH HIGH RISK PROSTATE CANCER AFTER RADICAL PROSTATECTOMY LONG-TERM FOLLOW-UP

2012 ◽  
Vol 187 (4S) ◽  
Author(s):  
Alexander W. Pastuszak ◽  
Amy M. Pearlman ◽  
Kumaran Sathyamoorthy ◽  
Joceline S. Liu ◽  
Larry I. Lipshultz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Replacement Therapy ◽  
Testosterone Replacement Therapy ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Long Term Follow Up
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