Comparability of CT-based and TRUS-based prostate volumes.

PURPOSE: To compare the prostate volumes defined by transrectal ultrasound (TRUS) versus computed tomographic (CT) scans used for brachytherapy planning. METHODS AND MATERIALS: Ten unselected patients underwent evaluation for prostate brachytherapy with TRUS and CT imaging. Axial prostate contours were obtained at 5-mm intervals in both studies. The CT images were photographed, scanned into a commercial software program, and reprinted from a laser printer at 600 dots per inch to provide individual images that were interpreted independently by the three physician authors (BK, KW, and JB). An effort was made to exclude pelvic floor muscles from the defined prostate contour. Volumes were calculated in cubic centimeters. The prostate volume and maximum dimension in each plane were compared for each imaging modality. RESULTS: The CT-based prostate volumes ranged from 31.1 cc to 48.1 cc. The TRUS-based volumes ranged from 26.6 cc to 46.4 cc. There was close agreement between imaging modalities (r = 0.9). The anterior-posterior, lateral, and craniocaudal prostatic dimensions were similar between modalities. To test for consistency between observers, the CT volumes were drawn independently by KB, KW, and JB. The prostatic measurements were consistent in all dimensions between observers. CONCLUSION: CT scan volumes and measurements correlate well with those obtained by TRUS, and are appropriate for pre- or postimplant dosimetry.

Use of TRUS to predict pubic arch interference of prostate brachytherapy.

PURPOSE: To demonstrate the potential for transrectal ultrasound (TRUS) to predict pubic arch interference of transperineal needle placement for prostate brachytherapy. METHODS AND MATERIALS: TRUS and pelvic computerized tomography (CT) scans from 22 patients who had transperineal prostate brachytherapy at University of Washington were analyzed for pubic arch visualization and interference. The outer margins of the prostate and the inner margins of the pubic bones from each imaging modality were outlined and compared. RESULTS: The pubic arch was readily visualized by TRUS in 21 of the 22 patients. There was good correlation between TRUS and CT for evaluating the amount of pubic arch interference (r = 0.90). CONCLUSION: TRUS can be substituted for CT imaging to evaluate pubic arch interference of transperineal needle placement for prostate brachytherapy. Eliminating routine CT scanning would reduce the cost of treatment.

Posttreatment biopsy results following interstitial brachytherapy in early-stage prostate cancer.

PURPOSE: To assess pathologic control rates for prostatic carcinoma as determined by postimplant prostate biopsy in a large series of consecutive patients who have received permanent interstitial brachytherapy using a contemporary transrectal ultrasound-directed, transperineal, computer generated, volume technique. METHODS AND MATERIALS: Four hundred and two patients received permanent 125I or 103Pd interstitial brachytherapy as primary treatment for early stage prostatic carcinoma at the Northwest Tumor Institute between January 1988 and January 1994. Of these, 201 have consented to biopsy 12 or more months postimplant with a median follow-up of 40 months (range: 12-83 months). None had received hormonal manipulation. A total of 361 biopsies was performed on 201 patients with a range of one to six annual biopsies per patient (91 received multiple, serial biopsies). Of the 161 patients more than 12 months postimplant who have not been biopsied, most have been unwilling or unable to submit to biopsy. Only six patients with biochemical progression have not been biopsied. There was no difference in the presenting characteristics or implant parameters between those patients biopsied and those that were not. One hundred and forty-three received 125I (71%) prescribed to a MPD of 160 Gy with a median activity of 35.5 mCi, and 58 (29%) received 103Pd prescribed to a MPD of 115 Gy with a median activity of 123 mCi. Multiple biopsies were performed under transrectal ultrasound guidance, and all specimens were classified as either negative, indeterminate, or positive. RESULTS: At the time of last biopsy, 161 (80%) have achieved negative pathology, 34 (17%) remain indeterminate, and 6 (3%) have been positive. Only 2 of the 186 patients with a PSA < 4.0 ng/ml at the time of biopsy were positive. Among those 33 indeterminate patients with a subsequent biopsy, 28 have converted to negative, 2 to positive, and 3 remain unchanged to date. CONCLUSIONS: These data demonstrate at least an 80% pathologically confirmed local control rate following permanent interstitial brachytherapy for early stage prostate cancer. A higher local control rate is expected with further follow-up as the majority of indeterminate biopsies convert to negative over time. The indeterminate category of postirradiation biopsy described here includes specimens that have probably been interpreted as positive in other series, but correlate clinically and biochemically with negative biopsies. These results support the use of modern interstitial brachytherapy techniques for selected patients with early stage adenocarcinoma of the prostate.

Retrospective stratification of a consecutive cohort of prostate cancer patients treated with a combined regimen of external-beam radiotherapy and brachytherapy.

PURPOSE: The evaluation of clinical variables that influence biochemical relapse-free survival in a cohort of patients treated by combined radiotherapy over a fixed interval. METHODS AND MATERIALS: Three hundred forty-eight patients diagnosed with clinical Stage T1--T3a prostate cancer were treated with a course of (103)Pd or (125)I brachytherapy followed by a limited course of external beam radiation formed the basis for study. All censored patients had a minimum 2-year follow-up. Biochemical relapse-free survival (BRFS) was estimated using a modified American Society for Therapeutic Radiology and Oncology consensus definition. Discrete "risk groups" were developed based on BRFS as influenced by pretreatment parameters. RESULTS: Significant risk factors contributing to biochemical failure were serum prostate-specific antigen (PSA) greater than 20 ng/mL, Gleason sum of 7 or greater, or clinical stage T2c or greater. Five-year biochemical control for those exhibiting no risk factor was 88%; one risk factor, 75%; two or more risk factors, 51%. The differences in BRFS among all three risk groups were statistically significant. Outcomes for patients presenting with PSA 10 to 20 ng/mL, but otherwise low-risk disease, fared no differently from those low risk patients presenting with PSA less than 10 ng/mL. CONCLUSIONS: Combined radiotherapy with (103)Pd or (125)I followed by external beam radiotherapy achieves a high rate of biochemical and clinical control in patients with low- to intermediate-risk clinically organ confined disease.

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.

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.

Use of pelvic CT scanning to evaluate pubic arch interference of transperineal prostate brachytherapy.

PURPOSE: To determine the necessity of preoperative evaluation of pubic arch interference in patients with small prostate volumes. METHODS AND MATERIALS: CT scans from 97 consecutive, unselected patients with stage T1 or T2 prostatic carcinoma who had transperineal I-125 or Pd-103 implants at the University of Washington in 1997 were analyzed for pubic arch interference. Transrectal ultrasound (TRUS) was performed with 6.0-MHz transducer with the patient in the lithotomy position and the patient's thighs vertical, similar to that used during the implant procedure. CT scans were obtained with the patient in the supine position, with 0.5-cm images taken at every 0.5 cm. To check for potential arch interference, the largest prostate cross-section was overlaid on the narrowest portion of the pubic arch. The overlap of the pubic arch and the prostate margin is measured at right angles to the inner pubic surface. The prostate volume obtained from the TRUS images was compared with the degree of pubic arch interference in order to determine whether TRUS volume predicted for interference. RESULTS: There was considerable variability in pubic arch interference between patients. The mm of pubic arch overlap with the prostatic margin varied from -11 mm to 20 mm. Patients with larger prostate volumes generally had more pubic arch interference, but the degree of interference was only loosely related to the prostate volume (r = 0.46). CONCLUSIONS: The degree of pubic arch interference is highly variable from one patient to the next and the TRUS volume cannot reliably predict patients who do or do not need a pelvic CT to detect potential arch interference.

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.

The interpretation of noisy data from archaeological field survey: Phosphate analysis.

High soil phosphate concentrations are commonly related to intense past human activity although full understanding of this relationship requires further research. At present, practical constraints in the field, the need for extensive sampling and for rapid results, leads to the archaeologist frequently using crude but portable techniques of chemical analysis. The problems associated with the collection and interpretation of archaeological soil phosphate data are discussed. The use of Bayesian change-point analysis is proposed as a suitable statistical aid to the interpretation of such data.

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.

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.

The role of androgen ablation in patients with biochemical or local failure after definitive radiation therapy: a survey of practice patterns of urologists and radiation oncologists in the United States.

To identify therapeutic patterns for putative prostate cancer treatment failures and the role played by androgen ablation therapy in these patients, a questionnaire study was undertaken with urologists and radiation oncologists who had attended a brachytherapy forum at the Seattle Prostate Institute (SPI). Hypothetical questions were asked about recommendations the physicians would give to a patient demonstrating biochemical or local failure after external-beam radiation therapy. Most of the physicians queried were in private practice; 53% were radiation oncologists and 47% were urologists. The respondents' recommendations for a hypothetical patient, who was 45 to 65 years of age, with a biopsy-proven local recurrence was treatment with androgen ablation (35% of respondents), radical prostatectomy (25%), interstitial brachytherapy (20%), and observation (19%). In the 65- to 75-year-old patient with a local recurrence, the respondents recommended observation (43%), androgen ablation (35%), interstitial brachytherapy (17%), and radical prostatectomy (4%). In patients receiving androgen ablation for a biochemical failure alone, there was no consensus on whether to use luteinizing hormone-releasing hormone agonist alone, total androgen ablation, orchiectomy, or intermittent androgen ablation. Criteria that prompted physicians to initiate androgen ablation were based on the rate of prostate-specific antigen (PSA) increase (67%), an absolute PSA number (24%), or clinical failure (9%). In the younger patient with a local recurrence, local intervention with radical prostatectomy or interstitial brachytherapy was recommended most often, followed by androgen ablation, then by observation. In the older patient, observation was recommended most often, followed closely by androgen ablation. Overall, there was a lack of consensus on how to deliver androgen ablation. However, there was remarkable agreement between urologists and radiation oncologists on virtually all issues queried.

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 iodine-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma.

BACKGROUND: This study was designed to evaluate the efficacy of iodine-125 interstitial radiation in the treatment of prostate carcinoma classified as T1 or T2. METHODS: One hundred twenty-six consecutive patients with adenocarcinoma of the prostate (T1, 23%; T2, 77%) were treated with iodine-125 radionuclides between January 1, 1988, and December 31, 1990. Four patients died of intercurrent illness within 1 year postimplant, leaving 122 men in the study. The prescribed minimum radiation dose was 160 gray. Median follow-up was 69.3 months. Prebiopsy prostate specific antigen (PSA) values (median, 5.0 ng/mL) were available for all patients. Posttherapy evaluation included clinical, biochemical (PSA), and pathologic (repeat needle biopsy) studies. No patient was surgically staged, and none received androgen deprivation therapy. Morbidity was graded according to the Radiation Therapy Oncology Group grading scale. Statistical appraisal was performed by the Kaplan-Meier method. PSA failure was defined in two ways: (1) PSA progression, i.e., 2 consecutive increases from a nadir value; and (2) failure to attain an arbitrary serum PSA value of 1.0 or 0.5 ng/mL at last follow-up. RESULTS: The overall 7-year survival was 77%; there were no deaths from prostate carcinoma in this cohort. The 7-year actuarial PSA progression free outcome was 89%, and the PSA < or = 1.0 ng/mL outcome was 87%. When PSA < or = 0.5 ng/mL was selected as an outcome end point, and PSA values in this series of radiation-treated patients were compared with PSA values proposed to indicate disease free survival after radical prostatectomy (PSA < or = 0.3-< or = 0.6 ng/mL), the 7-year actuarial disease free survival was 79%. Morbidity was minimal except in patients who had preimplant or postimplant transurethral prostate resection. CONCLUSIONS: Outpatient-based iodine-125 prostate brachytherapy for prostate carcinoma classified as T1 or T2 resulted in biochemical outcomes comparable to end points resulting from radical prostatectomy and external beam radiation.

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.

Neoadjuvant Androgen Ablation Combined with External-Beam Radiation Therapy and Permanent Interstitial Brachytherapy Boost in Localized Prostate Cancer.

Androgen ablation therapy has been combined with permanent interstitial brachytherapy in order to downsize the gland prior to seed implantation. It also has been employed in an attempt to improve the effectiveness of therapy in patients with a poor prognosis. We report on 50 patients consecutively treated and prospectively followed. All received neoadjuvant hormonal therapy (NHT) and 45 Gy of external-beam therapy to a limited pelvic field, followed by permanent implantation of (125)I or (103)Pd seeds. The median follow-up is 42.1 months (range 9.0-90.8 months). The prostate specific antigen (PSA) progression-free survival rate (<1.0 ng/mL) was 76% at 5 years (Kaplan-Meier method). Local control was achieved in 100% of the patients and distant disease-free survival in 85%. High-risk patients treated contemporaneously with these patients, who received external-beam radiation and a seed boost without NHT, had a 62% rate of 5-year PSA progression-free survival. Although the modest improvement in PSA progression-free survival is not statistically significant at 5 years (P = 0.5), the patients treated with NHT in addition to combined radiotherapy presented with significantly higher serum PSA concentrations (mean 21.0 ng/mL; median 17.0 ng/mL) than those treated with combination radiotherapy alone (mean 15.6 ng/mL; median 10.6 ng/mL) and thus had a worse prognosis.