Pretreatment nomogram for predicting freedom from recurrence after permanent prostate brachytherapy in prostate cancer.

OBJECTIVES: To develop a prognostic nomogram to predict the freedom from recurrence for patients treated with permanent prostate brachytherapy for localized prostate cancer. METHODS: We performed a retrospective analysis of 920 patients treated with permanent prostate brachytherapy between 1992 and 2000. The clinical parameters included clinical stage, biopsy Gleason sum, pretreatment prostate-specific antigen (PSA) value, and administration of external beam radiation. Patients who received neoadjuvant androgen deprivation therapy were excluded. Failure was defined as any post-treatment administration of androgen deprivation, clinical relapse, or biochemical failure, defined as three PSA rises. Patients with fewer than three PSA rises were censored at the time of the first PSA rise. Data from two outside institutions served as validation. RESULTS: A nomogram that predicts the probability of remaining free from biochemical recurrence for 5 years after brachytherapy without adjuvant hormonal therapy was developed using Cox proportional hazards regression analysis. External validation revealed a concordance index of 0.61 to 0.64, and calibration of the nomogram suggested confidence limits of +5% to -30%. CONCLUSIONS: The pretreatment nomogram we developed may be useful to physicians and patients in estimating the probability of successful treatment 5 years after brachytherapy for clinically localized prostate cancer.

10-year biochemical (prostate-specific antigen) control of prostate cancer with (125)I brachytherapy.

PURPOSE: To report 10-year biochemical (prostate-specific antigen [PSA]) outcomes for patients treated with 125I brachytherapy as monotherapy for early-stage prostate cancer. METHODS AND MATERIALS: One hundred and twenty-five consecutively treated patients, with clinical Stage T1-T2b prostate cancer were treated with 125I brachytherapy as monotherapy, and followed with PSA determinations. Kaplan-Meier estimates of PSA progression-free survival (PFS), on the basis of a two consecutive elevations of PSA, were calculated. Aggregate PSA response by time interval was assessed. Comparisons were made to an earlier-treated cohort. RESULTS: The overall PSA PFS rate achieved at 10 years was 87% for low-risk patients (PSA < 10, Gleason Sum 2-6, T1-T2b). Of 59 patients (47%) followed beyond 7 years, 51 (86%) had serum PSAs less than 0.5 ng/mL; 48 (81%) had serum PSAs less than 0.2 ng/mL. Failures were local, 3.0%; distant, 3.0%. No patients have died of prostate carcinoma. The proportion of patients with a PSA < or =0.2 ng/mL continued to increase until at least 7-8 years posttherapy. A plot of PSA PFS against the proportion of patients achieving serum PSA of less than 0.2 ng/mL suggests a convergence of these two endpoints at 10 years. Patients treated in the era of this study (1988-1990) experienced a statistically improved PFS compared with an earlier era (1986-1987). This difference appears independent of patient selection, suggesting that the maturation of the technique resulted in improved biochemical control. CONCLUSION: With modern technique, monotherapy with 125I achieves a high rate (87%) of biochemical and clinical control in patients with low-risk disease at 10 years. The decline of PSA following brachytherapy with low-dose-rate isotopes can be protracted. Absolute PSA and PFS curves merge, and are comparable at 10 years.

The role of external beam radiotherapy with I-125/Pd-103 brachytherapy for prostate carcinoma.

BACKGROUND AND PURPOSE: To compare the biochemical outcomes of patients treated with Pd-103/I-125 brachytherapy alone vs. brachytherapy combined with external beam radiotherapy for early stage prostate carcinoma. METHODS: Brachytherapy monotherapy was used in 403 patients. Brachytherapy was combined with 45 Gy of external beam radiotherapy in 231 patients. Median follow-up was 58 months. To compare the biochemical outcomes of these two treatment approaches, patients were stratified into three relative risk groups: low risk, T(1)-T(2), Gleason 2-6/10, PSA< or =10.0; intermediate risk, T(3), Gleason 7-10/10, PSA>10.0 (one factor); high risk, T(3), Gleason 7-10/10, PSA>10.0 (two factors). RESULTS: The actuarial biochemical progression-free rate (bNED) for the entire 634 patients was 85% at 10 years. The bNED outcomes by risk group for monotherapy vs. combined therapy respectively were: low risk, 94 vs. 87%; intermediate risk, 84 vs. 85%; high risk, 54 vs. 62%. These differences did not reach statistical significance for any risk group. Rectal morbidity was slightly greater in the combined treatment patients. CONCLUSION: Although the addition of external beam irradiation to brachytherapy is conceptually appealing for patients with higher risk prostate carcinoma, we were unable to demonstrate a benefit. Whether this is because of patient selection biases within the risk groupings, an artefact of retrospective review, or because external radiotherapy does not offer additional benefit is uncertain.

Short-course androgen ablation combined with external-beam radiation therapy and low-dose-rate permanent brachytherapy in early-stage prostate cancer: a matched subset analysis.

BACKGROUND AND PURPOSE: In order to evaluate the effect of short-term androgen blockade on biochemical control rates for high-risk patients receiving a combination regimen of external-beam radiation therapy and low-dose-rate permanent seed implant brachytherapy, a retrospective matched subset analysis was performed. PATIENTS AND METHODS: Inclusion in the high-risk cohort required at least two of the following poor prognostic factors: serum prostate specific antigen (PSA) concentration > or = 10.0 ng/mL, Gleason score > or = 7, or clinical stage T(2c) or T(3a) disease. Twenty-one patients who underwent androgen ablation between June 1991 and December 1995 in addition to combined-modality radiation therapy qualified as high risk, as did 77 patients who underwent combined-radiation therapy only. There was no statistically significant difference between the two groups in terms of follow-up (mean 44.6 v 47.8 months, respectively), pretreatment PSA, clinical stage, biopsy Gleason score, or the presence of all three poor prognostic factors. RESULTS: The overall rates of freedom from biochemical failure at 5 years were 77% in the hormonally treated group and 58% in the nonhormonally treated group. The difference was not statistically significant by log rank test (P = 0.08). CONCLUSION: Longer follow-up with larger patient numbers is needed to define the role of adjuvant androgen ablation combined with radiation therapy.

Transient elevation of serum prostate-specific antigen following (125)I/(103)Pd brachytherapy for localized prostate cancer.

Based on suggestions by anecdotal evidence to date, an attempt is made to estimate the occurrence of non-disease-related prostate-specific antigen (PSA) spiking in the serum PSA profiles of a series of men treated by (125)I/(103)Pd brachytherapy with or without external beam irradiation. Five hundred ninety-one patients treated between January 1988 and December 1993 were eligible for study. Patients whose clinical status was described as equivocal (declining PSA > 1.0 ng/mL or rising PSA without documented disease [9.6% of the cohort]) were not considered. Evidence of PSA increases that were followed by decline were identified. Treatment and disease-specific parameters were examined for influence of the occurrence of spiking. In patients judged biochemical successes at last follow-up (serum PSA < or = 1.0 ng/mL), 35.8% exhibited a temporary increase of 0.2 ng/mL or more. Seventy-five percent of these patients exhibited a temporary increase between 0.3 and 3.4 ng/mL. The average time of the temporary increases was 24.8 months after implant. Spiking was not associated with a higher risk of clinical failure in this data set. Conventional risk factors for recurrent disease were not associated with benign PSA spiking. Low-magnitude serum PSA spiking may occur in up to one third of patients following permanent, low-dose rate brachytherapy of the prostate. Most of these observations occur up to 3 years after implant and do not appear to be related to disease recurrence. Caution should be taken before initiating further therapy pursuant to the observation of PSA spiking of less than 2 to 3 ng/mL shortly following brachytherapy. Frequent serum PSA sampling following prostate brachytherapy with early follow-up may overestimate biochemical failure rates.

Palladium-103 brachytherapy for prostate carcinoma.

PURPOSE: A report of biochemical outcomes for patients treated with palladium-103 (Pd-103) brachytherapy over a fixed time interval. METHODS AND MATERIALS: Two hundred thirty patients with clinical stage T1-T2 prostate cancer were treated with Pd-103 brachytherapy and followed with prostate-specific antigen (PSA) determinations. Kaplan-Meier estimates of biochemical failure on the basis of two consecutive elevations of PSA were utilized. Multivariate risk groups were constructed. Aggregate PSA response by time interval was assessed. RESULTS: The overall biochemical control rate achieved at 9 years was 83.5%. Failures were local 3.0%; distant 6.1%; PSA progression only 4.3%. Significant risk factors contributing to failure were serum PSA greater than 10 ng/ml and Gleason sum of 7 or greater. Five-year biochemical control for those exhibiting neither risk factor was 94%; one risk factor, 82%; both risk factors, 65%. When all 1354 PSA determinations obtained for this cohort were considered, the patients with a proportion of PSAs < or = 0.5 ng/ml continued to increase until at least 48 months post-therapy. These data conformed to a median PSA half-life of 96.2 days. CONCLUSIONS: Prostate brachytherapy with Pd-103 achieves a high rate of biochemical and clinical control in patients with clinically organ-confined disease. PSA response following brachytherapy with low-dose-rate isotopes is protracted.

Permanent prostate seed implant brachytherapy: report of the American Association of Physicists in Medicine Task Group No. 64.

There is now considerable evidence to suggest that technical innovations, 3D image-based planning, template guidance, computerized dosimetry analysis and improved quality assurance practice have converged in synergy in modern prostate brachytherapy, which promise to lead to increased tumor control and decreased toxicity. A substantial part of the medical physicist's contribution to this multi-disciplinary modality has a direct impact on the factors that may singly or jointly determine the treatment outcome. It is therefore of paramount importance for the medical physics community to establish a uniform standard of practice for prostate brachytherapy physics, so that the therapeutic potential of the modality can be maximally and consistently realized in the wider healthcare community. A recent survey in the U.S. for prostate brachytherapy revealed alarming variance in the pattern of practice in physics and dosimetry, particularly in regard to dose calculation, seed assay and time/method of postimplant imaging. Because of the large number of start-up programs at this time, it is essential that the roles and responsibilities of the medical physicist be clearly defined, consistent with the pivotal nature of the clinical physics component in assuring the ultimate success of prostate brachytherapy. It was against this background that the Radiation Therapy Committee of the American Association of Physicists in Medicine formed Task Group No. 64, which was charged (1) to review the current techniques in prostate seed implant brachytherapy, (2) to summarize the present knowledge in treatment planning, dose specification and reporting, (3) to recommend practical guidelines for the clinical medical physicist, and (4) to identify issues for future investigation.

Reduction of radioactive seed embolization to the lung following prostate brachytherapy.

PURPOSE: Ultrasound-guided interstitial implantation of radioactive seeds is a common treatment for early stage prostate cancer. One of the risks associated with this therapy is seed embolization to the lung. This paper reports on the incidence and possible adverse effects of seed migration. METHODS AND MATERIALS: Two hundred ninety consecutive patients were treated with permanent radioactive seed brachytherapy for prostate cancer between January 1 and December 31, 1995. One hundred fifty-four patients were treated with iodine-125 (I-125), and 136 patients were treated with palladium-103 (Pd-103). All but one patient had a routine post implant chest radiograph (CXR), leaving 289 evaluable patients. RESULTS: Twenty radioactive seed pulmonary emboli were identified in 17 patients; 3 patients had two emboli each. The radioactive seed pulmonary embolism rate for the entire group of patients was 5.9%. Acute pulmonary symptoms were not reported by any patient in this series. One hundred forty-six study patients were implanted with free seeds alone (136 Pd-103 and 11 I-125), and 143 were implanted with linked seed embedded in a vicryl suture for the peripheral portions of their implants. The radioactive seed embolization rate by patient was 11% (16/146) versus 0.7% (1/143) for free seed implants and implants utilizing linked seeds, respectively. The difference was statistically significant, p = 0.0002. No patient had detectable morbidity as a consequence of seed emboli. CONCLUSION: The use of linked seeds embedded in vicryl sutures for the peripheral portion of permanent radioactive seed prostate implants significantly reduced the incidence of pulmonary seed embolization in patients treated with the Seattle technique.

Centralized multiinstitutional postimplant analysis for interstitial prostate brachytherapy.

PURPOSE: To investigate the feasibility and utility of performing centralized postimplant analysis for transperineal interstitial permanent prostate brachytherapy (TIPPB) by conducting a pilot study that compares the results obtained from 125I implants conducted at five different institutions. METHODS AND MATERIALS: Dose-volume histogram (DVH) analysis was performed on 10 postimplant CT scans from each of five institutions. This analysis included the total implanted activity of 125I, ultrasound, and CT volumes of the prostate, target-volume ratios, dose homogeneity quantifiers, prostate dose coverage indices, and rectal doses. As a result of the uncertainty associated with the delineation of the prostatic boundaries on a CT scan, the contours were redrawn by a single, study center physician, and a repeat DVH analysis was performed. This provided the basis for comparison between institutions in terms of implant technique and quality. RESULTS: By comparing total activity to preimplant ultrasound volume we clearly demonstrated that differences exist in implant technique among these five institutions. The difficulty associated with determining glandular boundaries on CT scans was apparent, based upon the variability in prostate volumes drawn by the various investigators compared to those drawn by the study center physician. This made no difference, of course, in the TVR or homogeneity quantifiers that are independent of target location. Furthermore, this variability made surprisingly little difference in terms of dose coverage of the prostate gland. Rectal doses varied between institutions according to the various implant techniques. CONCLUSIONS: Centralized, outcome-based evaluation of transperineal interstitial permanent prostate brachytherapy is viable and appropriate. Such an approach could be reasonably used in the conduct of multiinstitutional trials used to study the efficacy of the procedure.

Brachytherapy for clinically localized prostate cancer: results at 7- and 8-year follow-up.

In recent years, there has been a resurgence of interest in interstitial radiation as a cost-effective and efficient method of treating organ-confined prostate cancer. We describe our 7- and 8-year results with transperineal Iodine-125 and Palladium-103 implantation. A total of 551 consecutive patients were treated. Of these, 320/551 (58%) received implant alone (Group I), and 231/551 (42%)--considered higher risk patients--were also treated with a modest dose (45 Gy) of external beam irradiation (Group II). The median follow-up for Group I was 55 months, and for Group II, 60 months. At 7 years, the actuarial freedom from biochemical failure (prostate-specific antigen (PSA) < or = 1.0 ng/mL) was 80% in Group I patients, and, at 8 years, 65% in Group II patients. Morbidity was minimal if patients had not undergone prior transurethral prostate resections. The results indicate that interstitial radiation is a valid treatment for clinically localized prostate cancer.

Interstitial implantation techniques in prostate cancer.

Brachytherapy is a radiotherapeutic technique that allows the physician to implant radioactive isotopes into a body cavity or directly into tissue. Different radioisotopes have unique characteristics that the brachytherapist may utilize for a particular situation. The use of brachytherapy is part of standard radiation oncology practice in gynecological and head and neck cancer management. The prostate is approachable for interstitial implantation due to its close proximity to the perineum. Over 20 years ago, primitive methods of brachytherapy were utilized in the treatment of prostate cancer. However, poor results due to inconsistency in achieving adequate coverage of the entire prostate and poor patient selection caused this treatment modality to fall out of favor. Technological advances over the last decade have restored attention to brachytherapy for prostate cancer. Particularly important has been the development of transrectal ultrasound, new radioisotopes such as palladium-103, computer tomography, computerized dosimetry systems, and earlier diagnosis. Modern interstitial implantation utilizing transperineal template and transrectal ultrasound guidance has resulted in improved consistency in radiation dose delivery to the entire prostate. Early results are encouraging in terms of the relatively low morbidity of the procedure, improved local control rates, and biochemical progression free survival. This has resulted in an outpatient treatment that has high patient acceptance.