Thymosin beta-15 predicts for distant failure in patients with clinically localized prostate cancer-results from a pilot study.

OBJECTIVES: To report the results of a pilot study on the prognostic value of a newly identified actin-binding protein, thymosin beta-15 (Tbeta15), in predicting prostate-specific antigen (PSA) and bone failure in patients with Gleason 6/10 clinically localized prostate cancer. METHODS: Thirty-two patients (median age 70 years) with clinically localized, moderately differentiated (Gleason 6/10) prostate cancer treated by external beam radiotherapy alone (68.4 Gy) with available paraffin blocks at the Massachusetts General Hospital were evaluated for this pilot study. All patients had clinical Stage M0 disease at initial presentation, which was documented by bone scan (T1c-4,NX). Their corresponding biopsy specimens were stained immunohistochemically for Tbeta15, which was then correlated with the clinical outcome in a blinded manner. The median follow-up was 6 years (range 1 to 19) for all of the patients. RESULTS: The outcomes of the 32 patients can be grouped into three categories: patients with no evidence of disease (n = 11), patients with PSA failure without documented bone failure (n = 11), and patients with PSA failure and documented bone failure (n = 10). Tbeta15 staining intensity strongly correlated with clinical outcome. Of those patients whose specimens stained 3+ (strongest staining), 62% developed bone failure compared with 13% of those patients whose specimens stained 1+ (weakest staining) (P = 0.01). The 5-year freedom from PSA failure was only 25% for those patients with 3+ staining compared with 83% for those with 1+ staining (P = 0.02). CONCLUSIONS: The results of this pilot study have demonstrated that Tbeta15 staining intensity may be a potentially important marker to identify high-risk patients with moderately differentiated, clinically localized prostate cancer.

The long-term effect on PSA values of incidental prostatic irradiation in patients with pelvic malignancies other than prostate cancer.

PURPOSE: To determine the effect of external beam radiation therapy on serum prostate-specific antigen (PSA) production by the benign prostate. METHODS AND MATERIALS: We studied a cohort of 24 men receiving treatment for cancer of the bladder or rectum. The radiation fields in all cases encompassed the prostate gland, and none of the patients were known to have prostate cancer. All patients had 2 or more PSA estimations obtained in the years following their radiation treatment. A second group of 46 patients who had undergone radical external beam radiation therapy for prostate cancer and who were clinically disease free 8-22 years later were also observed, with a median of 5.8 years of PSA observations. RESULTS: Only 3 of the 24 patients in the first group showed a significant rise of > 0.2 ng/ml in their serum PSA levels, with a median of 3.3 years follow-up from the first PSA test. Seven of 24 showed progressive declines, and 14 of 24 showed steady levels. The median PSA for this group was < or = 0.5 ng/ml. Only 6 of the 46 in the second group showed a PSA rise of > 0.2 ng/ml. Thirty-four had stable values, and 6 had further declines. Again, the median PSA for the entire group was < or = 0.5 ng/ml. CONCLUSION: Recovery of prostatic secretory function is an uncommon event after external beam radiation. The concern that this might significantly confound new definitions of biochemical failure after radical radiation for prostate cancer that are based on progressively rising PSA values thus appears to be unfounded.

A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-fluorouracil and twice daily radiation followed by selective bladder preservation in operable patients with muscle invading bladder cancer.

PURPOSE: We describe a protocol designed to evaluate the use of twice daily radiation used together with cisplatin and 5 fluorouracil (5-FU) in the treatment of operable transitional cell carcinoma of the bladder with potential bladder preservation. MATERIALS AND METHODS: A total of 18 consecutive patients with T2-T4a bladder tumors underwent as complete a transurethral resection as possible, which was visibly complete in 14 cases. They then received twice daily radiation and infusion cisplatin and 5-FU during an induction phase. No therapy was given for 3 weeks, following which patients were reevaluated cystoscopically. Cases of clinical complete response by biopsy and cytology were consolidated with further chemotherapy/radiation using the same chemotherapeutic agents and radiation schedule. Patients who had incomplete responses were advised to undergo an immediate radical cystectomy. Of the 18 patients 15 subsequently received 3 cycles of adjuvant chemotherapy, consisting of methotrexate, cisplatin and vinblastine. Median followup for the entire group is 32 months. RESULTS: Of the 18 patients 14 had no detectable tumor after induction therapy. Of the 4 patients with persistent tumor 2 underwent radical cystectomy and 2 refused cystectomy, 1 of whom was treated with partial cystectomy and the other with consolidation chemotherapy/radiation. The actuarial overall survival at 3 years was 83%. The chance of a patient being alive at 3 years with a native bladder was 78%. No patient required cystectomy for hematuria or bladder shrinkage. Three patients in whom superficial tumors developed were treated successfully with bacillus Calmette-Guerin. Small bowel obstruction in 1 case was corrected surgically. CONCLUSIONS: This pilot study demonstrates a high rate of response to this combined chemotherapy/radiation regimen in conjunction with a visibly complete transurethral resection. Reevaluation after a short induction phase allows for the early selection of patients with persistent disease for radical cystectomy.