Adjuvant Leuprolide With or Without Docetaxel in Patients With High-Risk Prostate Cancer After Radical Prostatectomy (TAX-3501)
ABSTRACT The current trial evaluated 2 common therapies for patients with advanced prostate cancer, docetaxel and hormonal therapy (HT), in the surgical adjuvant setting.
TAX-3501 was a randomized, phase 3, adjuvant study post-radical prostatectomy (RP) in high-risk patients with prostate cancer (n = 228) comparing 18 months of HT with (CHT) without docetaxel chemotherapy either immediately (I) or deferred (D). High-risk disease was defined as a 5-year freedom-from-disease-progression rate of ≤ 60% as predicted by a post-RP nomogram. Progression-free survival (PFS), including prostate-specific antigen disease recurrence, was the primary endpoint. The authors also assessed the accuracy of the nomogram and analyzed testosterone recovery in 108 patients treated with HT who had at least 1 posttreatment testosterone value.
Between December 2005 and September 2007, 228 patients were randomized between the treatment cohorts. TAX-3501 was terminated prematurely because of enrollment challenges, leaving it underpowered to detect differences in PFS. After a median follow-up of 3.4 years (interquartile range, 2.3-3.8 years), 39 of 228 patients (17%) demonstrated PSA disease progression, and metastatic disease progression occurred in 1 patient. The median time to baseline testosterone recovery after the completion of treatment was prolonged at 487 days (95% confidence interval, 457-546 days). The nomogram's predicted versus observed freedom from disease progression was significantly different for the combination D(HT) and D(CHT) group (P < .00001).
TAX-3501 illustrated several difficulties involved in conducting postoperative adjuvant systemic trials in men with high-risk prostate cancer: the lack of consensus regarding patient selection and treatment, the need for long follow-up time, nonvalidated intermediate endpoints, evolving standard approaches, and the need for long-term research support. Except for selected patients at very high-risk of disease recurrence and death, surgical adjuvant trials in patients with prostate cancer may not be feasible. Cancer 2013. © 2013 American Cancer Society.
[Show abstract] [Hide abstract]
ABSTRACT: We studied 721 men with clinically confined disease who underwent radical prostatectomy. No patient received preoperative or postoperative radiotherapy or hormone therapy until progression occurred. For those men without progression, the mean follow-up was 6.5 years with a median of 6 years (range 1 to 12 years). Because patients with lymph node metastases or seminal vesicle invasion had such a high risk of progression, enhanced prognostication was not needed in men with these findings. Thus we focused this analysis on the 617 men without lymph node metastases or seminal vesicle invasion. In the multivariate analysis, Gleason score (P < 0.0001), surgical margins (P = 0.004), and capsular penetration (P = 0.007) were all independent predictors of progression. Tumors with a Gleason score of 2 through 4 were almost invariably cured, with a 10-year progression-free risk of 96%. At the opposite end of the spectrum, the 10-year actuarial progression-free risk for men with a Gleason score of 8 through 9 was 35%. Men with Gleason score 2 through 4 or 8 through 9 tumors could not be stratified into different risks of progression based on the presence or extent of capsular penetration or margin status. For the men with Gleason score 5 through 7 tumors (88.2% of cases), predicting their risk of progression was enhanced by knowledge of their tumor's capsular penetration and margin status. Tumors with a Gleason score of 5 through 6 and 7 were each stratified into three groups with different risks of progression. Using the actuarial curves within this study, physicians will be able to more accurately determine a patient's risk of progression following radical prostatectomy based on a combination of the radical prostatectomy Gleason score, extent of capsular penetration, and status of surgical margins of resection.American Journal of Surgical Pathology 04/1996; 20(3):286-92. DOI:10.1097/00000478-199603000-00004 · 4.59 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated. In 1987, the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm. Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03). Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.Journal of Clinical Oncology 04/1997; 15(3):1013-21. · 17.88 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: An undetectable prostate-specific antigen level is the gold standard for tumor-free status in the follow-up evaluation of men after radical retropubic prostatectomy. The authors report their experience with 1623 patients treated at The Johns Hopkins Hospital since 1982. Clinical and pathologic parameters that have an effect on recurrence after radical prostatectomy are described. Preservation of sexual function is shown not to have an adverse influence on cancer control. The timing of prostate-specific antigen recurrence, a high Gleason score, and involvement of the seminal vesicles or pelvic lymph nodes all are shown to be important variables in predicting local versus distant failure after radical prostatectomy.Urologic Clinics of North America 06/1997; 24(2):395-406. DOI:10.1016/S0094-0143(05)70386-4 · 1.35 Impact Factor