Post-treatment Prostate-specific Antigen Research Articles

Brachytherapy and organ preservation in the management of carcinoma of the prostate

The treatment of organ-confined carcinoma of the prostate with permanent radioisotopes by the retropubic method has generated variable and controversial results. In this article, the technical flaws of the retropubic approach are discussed. Issues of radiobiological factors, dose inhomogeneity, and case selection are addressed relative to the reported results. Recent advances in radioisotope development, computer based dosimetry, and transrectal ultrasound and computed tomographic imaging have fostered techniques of closed transperineal implantation that produce a more homogeneous, reproducible, and larger volume implant with a higher peripheral dose rate than was possible in the past. With a median follow-up of 37 months (range 12 to 78 months), 93% of 291 early stage A-B patients treated with (125)I or (130)Pd alone showed a normal posttreatment prostate-specific antigen (PSA) (median value 0.4). In 160 more advanced stage A-C patients treated with external beam irradiation and implant boost, 85% showed a normal PSA (median value 0.3). The elimination of surgery with these techniques permits outpatient treatment resulting in high patient acceptance. If longer follow-up substantiates the favorable early results, these methods may potentially offer the least morbid and least expensive method of treatment for early stage carcinoma of the prostate.

Prostate-specific antigen. An important marker for prostate cancer treated by external beam radiation therapy

Prostate-specific antigen (PSA) is a valuable serum marker for prostate cancer. However, the prognostic importance of baseline PSA values in relation to other prognostic factors has not been elucidated. The incidence of postradiation rising PSA values has not been documented, and the extent to which PSA influences the assessment of radiation therapy is unclear. This study was designed to address these issues. Three hundred and fourteen consecutive patients with baseline PSA values who were treated between 1987 and 1991 with external beam radiation alone were reviewed for disease outcome and posttreatment PSA levels. Clinical stages at diagnosis were: Stage A2, 87 (28%); Stage B, 108 (34%); and Stage C, 119 (38%). At a mean follow-up of 21 months, 25 patients had relapsed, 53 had developed rising PSA profiles, and 58 had either relapsed or had rising PSA profiles. The actuarial relapse rate was 20% at 4 years, the incidence of rising PSA profiles was 38% at 4 years, and the incidence of either relapse or rising PSA was 40% at 4 years. In multivariate analysis, baseline PSA value was the single most important factor predicting for local relapse, metastatic relapse, any disease relapse, and posttreatment rising PSA values. Using relapse or rising PSA as endpoints, the following four prognostic groupings based on baseline PSA and M.D. Anderson (MDA) grade were delineated: I, PSA less than or equal to 4 ng/ml, any grade; II, PSA greater than 4 but less than or equal to 10 ng/ml, Grades 1 and 2; III, PSA greater than 4 but less than or equal to 10 ng/ml, Grades 3 and 4 or PSA greater than 10 but less than or equal to 30 ng/ml, Grades 1 and 2; and IV, PSA greater than 10 but less than or equal to 30 ng/ml, Grades 3 and 4 or PSA greater than 30 ng/ml, any grade. The actuarial incidence of relapse or rising PSA in these groups was: I, less than 10% at 3 years; II, 20% at 3 years; III, 55% at 3 years; and IV, 90% at 30 months. When using traditional endpoints of disease outcome, the patients in this series had an outcome equivalent to that in 799 patients treated in our institution in the pre-PSA era; when using rising PSA profiles as endpoints, treatment was significantly less effective. Pretreatment serum PSA level is the single most significant predictor of disease outcome after radiation therapy for local-regional prostate cancer. Moreover, postirradiation PSA values may potentially serve as an early endpoint to evaluate treatment efficacy. Using a rising posttreatment PSA profile as an index of treatment failure reveals that total and permanent eradication of prostate cancer with radiation therapy alone is not achieved as often as previously believed and that multimodal treatment approaches to prognostically unfavorable early stage disease need investigation.

Current status of prostate-specific antigen in the radiotherapeutic management of prostatic cancer

The current data involving the use of prostate-specific antigen (PSA) in the radiotherapeutic management of localized prostatic cancer is reviewed. Controversies and ongoing debate notwithstanding, a number of general conclusions have been made. (1) PSA as a screening test has increased prostate cancer detection rates and is recommended as part of routine screening to supplement digital rectal examination. (2) Preradiotherapy PSA levels are correlated with tumor stage but also provide prognostic information that is independent of tumor stage and histological grade. (3) Following the completion of radiotherapy, PSA levels must decline to normal values to assure a successful treatment outcome. Disagreement persists as to what constitutes a normal PSA value after radiotherapy, and in what time frame after treatments such a level must be achieved. (4) Different proposed models of PSA decline after radiotherapy are discussed, but it remains premature to assess their relative success as predictors of subsequent clinical events. (5) Postradiotherapy prostate biopsy results (negative versus positive) correlate reasonably well with post-treatment PSA status (normal versus elevated). (6) The management of patients with a rising PSA following radiotherapy must be individualized, with early hormonal intervention being an attractive, although unproven, therapeutic option for selected patients. (7) PSA data confirm the value of adjuvant radiotherapy for positive surgical margins and strengthens the indications for its use. (8) Preliminary data regarding PSA levels following transperineal interstitial brachytherapy implantation of the prostate appear favorable.

Prostate Specific Antigen after External Beam Radiotherapy for Prostatic Cancer: Followup

Between 1986 and 1989, 117 patients with pretreatment and serial posttreatment prostate specific antigen values received external beam radiotherapy at our hospital. Followup ranged from 0.6 to 5.9 years (mean 2.7). No patient had hormonal manipulation before distant recurrence. Biochemical relapse, defined as an increasing prostate specific antigen level after treatment, was observed in 44 patients. To date 30 of these 44 patients (68%) have had clinical relapse. The prognostic factors of advanced local stage, high Gleason score and high elevations of pretreatment prostate specific antigen values predicted for biochemical relapse and subsequent clinical failure. The interval between biochemical and clinical relapse was 156 ± 46 days. Biochemical relapse is an important end point that can be used to determine the effect of treatment in prostatic cancer research.

The Clinical Usefulness of Serum Prostate Specific Antigen After Hormonal Therapy of Metastatic Prostate Cancer

We longitudinally followed serum prostate specific antigen (PSA) levels in 48 patients who were treated with either orchiectomy, monthly luteinizing hormone-releasing hormone injection or continuous diethylstilbestrol for stage D2 prostate adenocarcinoma and achieved an objective response. Of the patients 34 had clinical evidence of disease progression (median remission duration 19 months). Median length of followup for the 14 patients who remained in remission was 42 months. Pretreatment performance status, pretreatment extent of metastases as measured by a bone scan and post-treatment nadir PSA level were univariately correlated with remission duration. After adjustment for the 2 former pretreatment variables, a highly significant independent effect of the nadir PSA level on remission duration persisted. Patients whose post-treatment nadir PSA level decreased below 4ng./ml. had a significantly longer remission duration than those whose nadir PSA remained elevated (median 42 versus 10 months, p <0.0001).No cases were observed to progress (as defined by our criteria independent of PSA level) while the serial post-treatment PSA levels continued to decrease or remained at a plateau after reaching the nadir. The time at which the PSA began to increase once the nadir was reached predated objective evidence of progression in all patients except 2 in whom the 2 events occurred simultaneously (mean lead time 7.3 ± 5.0 months). We conclude that following serial PSA levels in patients treated with androgen ablation for metastatic prostate cancer can aid in distinguishing favorable from nonfavorable responders early in the course of therapy and greatly assist in monitoring for progression.

Prostate-specific antigen as a prognostic factor for prostate cancer treated by external beam radiotherapy

The potential prognostic significance of prostate-specific antigen (PSA) serum concentrations was evaluated in 171 patients with stages A2 to C adenocarcinoma of the prostate treated with external beam radiotherapy. After a median follow-up of 17 months, 12 patients sustained relapse of disease and PSA levels were found to be prognostically significant in three ways. (a) Pretreatment PSA level: none of 59 patients with a pretreatment PSA level ≤ 4 ng/ml relapsed to date and only one developed a subsequently rising PSA profile; 7 of 102 patients (7%) with a pretreatment PSA level in the range 4–40 ng/ml relapsed and 17 (17%) showed a rising PSA profile; 5 of 10 patients (50%) with a pretreatment PSA level ≥ 40 ng/ml relapsed and six (60%) developed rising PSA values. The differences were significant and were maintained when patients were stratified by stage or grade. (b) PSA level at 6 months: for patients with pretreatment PSA levels in the range 4–40 ng/ml, a 6-month value >2 ng/ml predicted a significantly worse outcome than a 6-month value < 2 ng/ml. (c) Rising post-treatment PSA values: following a radiation-related nadir in PSA levels, 24 patients experienced rising PSA values and 8 (33%) relapsed at a median time of 5 months after onset of the rising values—a significantly higher relapse rate than observed in patients with non-rising PSA values. Whether the majority, or all, of the patients with rising PSA levels relapse, requires further follow-up. In conclusion, serum PSA levels are strong prognostic determinants of outcome following radiotherapy for prostate cancer and appear to add prognostic information independently of tumor stage and grade.

Prostate Specific Antigen after Irradiation for Prostatic Carcinoma

The clinical significance of serum prostate specific antigen after primary irradiation for adenocarcinoma of the prostate is uncertain. Between September 1986 and December 1987 serial prostate specific antigen values were determined in 43 patients before and after definitive radiation therapy. The study group included 6 patients with stage TOd, 10 with stage T1, 11 with stage T2 and 16 with stage T3 disease, with a mean pre-treatment prostate specific antigen level of 49.2 ± 10.8. For all patients the first post-treatment prostate specific antigen level was less than the pre-treatment level. One patient failed locally with recurrent prostatic cancer that invaded the rectum. The 6 patients who failed with symptomatic metastases had an increasing prostate specific antigen level 2 to 7 months before detection of recurrence. Based on the absolute value and trend of the prostate specific antigen, patients were described as being at high, intermediate or low risk for distant metastases. Of 9 high, 6 intermediate and 28 low risk patients 4 (44%), 2 (33%) and 0 (0%) have experienced recurrent disease (p = 0.0025). We conclude that serial post-irradiation prostate specific antigen values may be useful in the early identification of patients at risk for treatment failure. (J. Urol., 144: 1172–1176, 1990)

Prostate-specific antigen: Monitoring the response of carcinoma of the prostate to radiotherapy with a new tumor marker

The role of prostate-specific antigen (PSA), a sensitive tumor marker for cancer of the prostate, has yet to be defined in patients treated with radiotherapy. To evaluate this, PSA and acid phosphatase (AP) were measured prospectively in 110 sequential patients who presented with locoregional carcinoma of the prostate and in whom radiotherapy was to be definitive treatment. Therapy was divided into the following treatment groups: external-beam radiotherapy alone (EBRT), EBRT with brachytherapy (EBRT + B), and hormone therapy either pre-EBRT or post-EBRT (EBRT + H). All patients have been followed for 1 to 17 months and a total of 521 posttreatment PSA determinations have been made. In 91 of 110 patients (83%) PSA was elevated pretreatment and correlated with clinical stage and subsequent relapse. There was no association with Gleason grade, assigned treatment group, or lymph node involvement. Acid phosphatase was elevated in only 31% of the patients initially and had no predictive value in subsequent failure. Nine patients have developed local and/or distant recurrence. None of the patients who failed had their PSA return to normal whereas 74 of 101 (73%) of the remainder have done so. Levels of PSA that do not return to normal during follow-up probably indicate active disease, often without evidence of clinical relapse. The authors conclude that PSA is a useful tumor marker for monitoring response to radiotherapy and may be a predictor of eventual failure thus identifying patients eligible for early intervention therapy as and when it becomes available.