Peter D. Grimm

AMERICAN BRACHYTHERAPY SOCIETY (ABS) RECOMMENDATIONS FOR TRANSPERINEAL PERMANENT BRACHYTHERAPY OF PROSTATE CANCER

PURPOSE/OBJECTIVE To develop and disseminate the American Brachytherapy Society (ABS) recommendations for the clinical quality assurance and guidelines of permanent transperineal prostate brachytherapy with 125I or 103Pd. METHODS AND MATERIALS The ABS formed a committee of experts in prostate brachytherapy to develop consensus guidelines through a critical analysis of published data supplemented by their clinical experience. The recommendations of the panels were reviewed and approved by the Board of Directors of the ABS. RESULTS Patients with high probability of organ-confined disease are appropriately treated with brachytherapy alone. Brachytherapy candidates with a significant risk of extraprostatic extension should be treated with supplemental external beam radiation therapy (EBRT). Patient selection guidelines were developed. Dosimetric planning of the implant should be carried out for all patients before seed insertion. A modified peripheral loading is preferred. The AAPM TG-43 recommendations requiring a change in prescription dose for 125I sources should be universally implemented. The recommended prescription doses for monotherapy are 145 Gy for 125I and 115-120 Gy for 103Pd. The corresponding boost doses (after 40-50 Gy EBRT) are 100-110 Gy and 80-90 Gy, respectively. Clinical evidence to guide selection of radionuclide (103Pd or 125I) is lacking. Post implant dosimetry and evaluation must be performed on all patients. It is suggested that the dose that covers 90% (D90) and 100% (D100) of the prostate volume and the percentage of the prostate volume receiving the prescribed dose (V100) be obtained from a dose-volume histogram (DVH) and reported. CONCLUSION Guidelines for appropriate patient selection, dose reporting, and improved quality of permanent prostate brachytherapy are presented. These broad recommendations are intended to be technical and advisory in nature, but the ultimate responsibility for the medical decisions rests with the treating physician. This is a constantly evolving field, and the recommendations are subject to modifications as new data becomes available.

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

Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group

Whats known on the subject? and What does the study add?

Prostate Specific Antigen Based Disease Control Following Ultrasound Guided sup 125 Iodine Implantation for Stage T1/T2 Prostatic Carcinoma

PURPOSE We report the prostate specific antigen (PSA) based recurrence-free survival rate after 125iodine (125I) implantation for early stage prostatic carcinoma. MATERIALS AND METHODS A total of 197 patients with clinical stage T1 and T2 prostatic carcinoma underwent outpatient 125I seed implantation. Followup was 1 to 7 years (median 3). Pretreatment serum PSA levels were elevated (greater than 4.0 ng./ml.) in 138 patients (70%). There were 105 well differentiated (Gleason score 2 to 4), 87 moderately differentiated (Gleason score 5 to 6) and 5 indeterminate tumors. The prescribed minimum prostatic dose was 160 Gy. The total dosage of 125I implanted ranged from 15 to 62 mCi. (median 37). Staging lymph node dissection and seminal vesicle biopsies were not routinely performed. RESULTS Among 138 patients with an elevated PSA level before implantation and no prior hormonal treatment, the PSA value returned to normal in 98% and decreased to less than 1.0 ng./ml. in 82% within 24 months of treatment. In 97% of those 138 patients the PSA level decreased to less than 1.0 ng./ml. at 48 months after implantation. Of 8 patients with an increasing PSA value 5 also had clinically evident failure. The actuarial rate of chemical (increasing PSA) or clinical failure at 5 years following implantation was 7%, with 15 patients still at risk at 5 years. There was a trend for higher failure rates among patients with higher pretreatment PSA levels (p = 0.57), Gleason scores 5 and 6 versus 2 to 4 (p = 0.51) or higher stage of disease (p = 0.17). CONCLUSIONS There is a high rate of clinical and chemical freedom from progression following 125I implantation for select patients with early stage prostatic carcinoma.

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.

American Brachytherapy Society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy

PURPOSE To provide updated American Brachytherapy Society (ABS) guidelines for transrectal ultrasound-guided transperineal interstitial permanent prostate brachytherapy (PPB). METHODS AND MATERIALS The ABS formed a committee of brachytherapists and researchers experienced in the clinical practice of PPB to formulate updated guidelines for this technique. Sources of input for these guidelines included prior published guidelines, clinical trials, published literature, and experience of the committee. The recommendations of the committee were reviewed and approved by the Board of Directors of the ABS. RESULTS Patients with high probability of organ-confined disease or limited extraprostatic extension are considered appropriate candidates for PPB monotherapy. Low-risk patients may be treated with PPB alone without the need for supplemental external beam radiotherapy. High-risk patients should receive supplemental external beam radiotherapy if PPB is used. Intermediate-risk patients should be considered on an individual case basis. Intermediate-risk patients with favorable features may appropriately be treated with PPB monotherapy but results from confirmatory clinical trials are pending. Computed tomography-based postimplant dosimetry performed within 60 days of the implant is considered essential for maintenance of a satisfactory quality assurance program. Postimplant computed tomography-magnetic resonance image fusion is viewed as useful, but not mandatory. CONCLUSIONS Updated guidelines for patient selection, workup, treatment, postimplant dosimetry, and followup are provided. These recommendations are intended to be advisory in nature with the ultimate responsibility for the care of the patients resting with the treating physicians.

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.

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.

SHOULD BRACHYTHERAPY BE CONSIDERED A THERAPEUTIC OPTION IN LOCALIZED PROSTATE CANCER

Contemporary prostate brachytherapy incorporates advances in computer analysis, imaging technology, and delivery apparatus, allowing exacting and reproducible results compared with historical approaches. The advances permit brachytherapy to be performed on a cost-effective, outpatient basis with low morbidity in the appropriately selected patient. Although unsettled questions remain regarding dosimetric issues, long-term outcomes, and morbidity, the weight of evidence to date appears to support the use of brachytherapy in selected patients. Brachytherapy may be considered a therapeutic option: as monotherapy for early-stage disease and also a boost following moderate doses of external beam irradiation for locally advanced disease.

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.