Undetectable prostate specific antigen at 6-12 months: a new marker for early success in hormonally treated patients after prostate brachytherapy.
BACKGROUND
The concept of a prostate-specific antigen (PSA) "nadir" has been used as a predictive marker for treatment success in patients treated with radiotherapy for localized prostate carcinoma. However, this approach is not applicable in patients who are concomitantly treated with short-term hormonal therapies. To address this, the authors sought to develop a new predictive marker in such patients after prostate brachytherapy (BT).


METHODS
Between March 1997 and November 2002, 194 men with clinical Stage T1A-T3N0M0 prostate carcinoma (according to the 1992 International Union Against Cancer/American Joint Committee on Cancer TNM classification system) were treated with interstitial palladium (103Pd3) BT and androgen ablation therapy with or without external beam radiotherapy (EBRT). Based on tumor characteristics, 127 patients received an antiandrogen, finasteride, and BT whereas 67 received an antiandrogen, leuprolide, and EBRT followed by a BT boost. Hormonal therapy was initiated 2-3 months before any radiotherapy for a total duration of 8-9 months. Follow-up included physical examination and determining the PSA level at 3-month intervals. Postoperative serum testosterone was evaluated in preoperatively potent patients with erectile dysfunction > 6 months after therapy. A PSA level < or = 0.06 ng/mL or < or = 0.20 ng/mL detected during a 6-12-month window after the implant were evaluated as predictors of biochemically disease-free survival (DFS), defined as the time to a PSA level > or = 1.0 ng/mL.


RESULTS
Of the 194 patients, 163 were available for analysis. The median length of follow-up was 48 months. In those patients with a PSA level < or = 0.20 ng/mL at 6-12 months, the DFS at 48 months after the implant was 96% (95% confidence interval [95% CI], 91-99%) compared with the remainder of the patients, whose DFS decreased to 80% (95% CI, 65-89%) (P < 0.001). When a PSA level < or = 0.06 ng/mL was used as an indicator, the 48-month DFS was 99% (95% CI, 91-100%) compared with that for patients with a PSA level > 0.06 ng/mL, in whom the DFS was 85% (95% CI, 74-92%) (P = 0.004). Furthermore, because testosterone levels may occasionally remain low after the cessation of luteinizing hormone-releasing hormone agonist therapy and result in erectile dysfunction and an artificially low PSA level, the authors reviewed the serum testosterone levels in 23 patients who were so treated and were experiencing erectile dysfunction. None had PSA values below the lower limit of normal.


CONCLUSIONS
A PSA level < or = 0.20 ng/mL or < or = 0.06 ng/mL measured at 6-12 months after BT appears to be a useful predictive marker for detecting early success in patients with prostate carcinoma who are treated with neoadjuvant androgen ablation and BT. These markers may be used to identify those patients who are at an increased risk of biochemical failure and may be useful in stratifying patients for closer follow-up, long-term adjuvant therapies, or clinical trials. A longer follow-up period will be needed to verify whether these are predictive of long-term cancer control.
Miller
Nicole
N
Department of Urology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Smolkin
Mark E
ME
Bissonette
Eric
E
Theodorescu
Dan
D
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000532:radiotherapy; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001918:Brachytherapy; D003131:Combined Modality Therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018120:Finasteride / Q000627:therapeutic use; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use; D008297:Male; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010165:Palladium / Q000627:therapeutic use; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000532:radiotherapy*; D011868:Radioisotopes / Q000627:therapeutic use; D012307:Risk Factors; D015996:Survival Rate; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D011868:Radioisotopes; D013739:Testosterone; D018120:Finasteride; D010165:Palladium; D017430:Prostate-Specific Antigen; D016729:Leuprolide