NEOADJUVANT CHEMOHORMONAL TAXANE-BASED THERAPY BEFORE RADICAL PROSTATECTOMY (RRP) IN HIGH-RISK PROSTATE CANCER: 4.4 YEARS' FOLLOW-UP OF A PHASE II TRIAL

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.

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Adjuvant multimodality treatment in patients with high-risk prostate cancer following radical prostatectomy: Results of a prospective clinical phase-II trial

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15557 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15557-15557

Author(s):

D. Thüer ◽

C. Ohlmann ◽

D. Pfister ◽

U. Engelmann ◽

A. Heidenreich

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Phase Ii Trial ◽

Multimodality Treatment ◽

Time To Progression ◽

Clinical Phase ◽

High Risk Prostate Cancer ◽

Psa Relapse ◽

Risk Prostate Cancer

15557 Background: High risk prostate cancer (PCA) is associated with a high frequency of PSA relapse. Even with adjuvant androgen deprivation therapy about 50% of patients experience systemic recurrences within 5 years. Docetaxel has demonstrated significant activity in men with metastatic androgen independent PCA, zoledronic acid has been shown to significantly inhibit the development of osseous metastases. It was the aim of the current prospective clinical phase-II trial to evaluate safety and clinical efficacy of early multimodality treatment in high risk PCA after radical prostatectomy (RPE). Methods: Between 3/2004 and 12/2005 25 patients with high risk PCA following RPE were recruited. High risk PCA was defined by a risk of biochemical progression > 70% according to the postoperative Kattan nomograms. Adjuvant therapy consisted of androgen deprivation with LHRH analogues for 12 months, zoledronic acid at 4mg every 3 months and docetaxel at 75 mg/qm for six consecutive cycles. Adjuvant treatment was initiated 4 to 6 weeks after surgery. Follow-up examination were undertaken every 3 months with PSA serum determinations; in case of PSA increase 2 consecutive measurements at 4 weeks intervals were performed. Time to progression defined the time interval between initiation of therapy and first PSA relapse. Results: The mean follow-up is 20.5 (6–31) months. Adjuvant multimodality treatment was well tolerated in all patients with grade 3/4 hematotoxicity in 3 (12%) and gastrointestinal toxicity in 5 (16%) patients; 2 (8%) developed significant oncolysis with surgical intervention. In none of the patients the dosage of docetaxel or the number of cycles had to be reduced. Currently, 4 (16%) patients have developed PSA relapse with 2 exhibiting osseous metastases and 2 having died. Median time to progression was 14.5 (10–16) months. Conclusions: The clinical efficacy appears to be lower than expected with a 16% progression rate and a 8% mortality rate after only 20 months of follow-up. Adjuvant multimodality treatment of high risk PCA after RPE can be applied without significant treatment-associated side effects. Currently ongoing clinical phase-III trials have to further validate the concept of adjuvant chemotherapy. No significant financial relationships to disclose.

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