Combined modality treatment in the management of high-risk prostate cancer

PURPOSE: The efficacy of a multimodality protocol using neoadjuvant and concomitant hormonal therapy, brachytherapy, and three-dimensional conformal external beam radiotherapy (RT) in high-risk prostate cancer was evaluated using biochemical outcomes and posttreatment biopsy results. METHODS AND MATERIALS: Between February 1994 and November 1999, 132 high-risk patients were treated with combined hormonal therapy (9 months), permanent radioactive seed brachytherapy, and external beam RT, with follow-up ranging from 36 to 88 months (median, 50 months). The eligibility criteria were any of the following: Gleason score 8-10, initial prostate-specific antigen (PSA) level >20 ng/mL, clinical Stage T2c-T3, or positive seminal vesicle biopsy, or two or more of the following: Gleason score 7, PSA level >10-20 ng/mL, or Stage T2b. Twenty percent of patients had a positive seminal vesicle biopsy before therapy. Negative laparoscopic pelvic lymph node dissections were performed in 44% of patients. RESULTS: The actuarial overall freedom from PSA failure rate was 86% at 5 years. The freedom from PSA failure rate at 5 years was 97% for those with a Gleason score of < or =6 (35 of 36), 85% for a Gleason score of 7 (50 of 59), and 76% for a Gleason score of 8-10 (28 of 37; p = 0.03). A trend was noted toward worse outcomes in seminal vesicle biopsy-positive patients, with a 5-year freedom from PSA failure rate of 74% vs. 89% for all other patients (p = 0.06). Posttreatment prostate biopsies were performed in 47 patients and were negative in 96% at the first biopsy and 100% at the last biopsy. CONCLUSION: Trimodality therapy with androgen suppression, brachytherapy, and external beam RT for high-risk prostate cancer results in excellent biochemical and pathologically confirmed local control.     

Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer

Background The indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy. Methods Between September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate ± seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60–66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml. Results The median follow-up period after radiation therapy was 33 months (range, 12–98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients. Conclusion Radiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate ± seminal vesicles, to a total dose of 60–66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe.     

Salvage reimplantation in patient with local recurrent prostate carcinoma after brachytherapy with three dimensional computed tomography-guided permanent pararectal implant

Thirty-one [31] patients with local recurrent or residual adenocarcinoma of the prostate, with no evidence of distant metastases, were treated with second permanent implant using a stereotactic three dimensional system and posterior pararectal CT-guided method. All patients had extensive under local anesthesia or IV sedation pararectal CT-guided biopsy of the prostate and seminal vesicles. All patients except one had 3 month neoadjuvant androgen ablation prior to salvage reimplantation. Twenty [20] of these patients had local recurrence in the prostate and eleven [11] patients had seminal vesicle invasion which was not diagnosed nor treated with the initial brachytherapy. In addition, the patients had PSA failure or local palpable disease, "cold spots" with CT imaging or areas of dosage less than 80% of the prescribed dose with DVH (dose volume histogram). Initial prescribed dose was 120 Gy with (103)Pd loose seeds in 26 patients and 144 Gy with (125)I loose seeds in 5 patients. For the reimplant the dosage in the recurrent site was 100-144 Gy with (125)I seeds in strand in 24 patients (77%) and 100-120 Gy with (103)Pd loose seeds in 7 patients (23%). The preference of (125)I seeds in the second treatment was because only (125)I in strand was available at the time of the reimplant. Eleven [11] patients had second implant twelve to twenty-four months after the initial implant and 20 patients had after twenty-five to eighty-seven months and median follow-up was thirty months. A high level of biochemical control (87%) was achieved in all of these patients who are recognized as high risk due to local recurrence. Four [4] patients experienced grade 2 or 3 GI or GU complications and two [2] patients experienced grade 4 GI complications. Patients with local recurrent prostate cancer following initial brachytherapy including those with seminal vesicle invasion can be successfully treated with pararectal stereotactic CT-guided reimplantation. Assessment of seminal vesicle status is an essential part of staging for local recurrence.     

Preliminary results of three-dimensional conformal radiotherapy as salvage treatment for a rising prostate-specific antigen level postprostatectomy

The purpose of this study is to determine the effectiveness of three-dimensional conformal radiotherapy delivered to the fossa of the prostate and seminal vesicles as salvage treatment for a prostate-specific antigen (PSA) level that becomes undetectable and subsequently begins to rise postprostatectomy. Between August 1994 and December 1997, 14 patients with prostate cancer whose PSA became undetectable after a radical prostatectomy subsequently developed a rising PSA, had no evidence of metastatic disease, and were treated with three-dimensional conformal radiotherapy at the University of California, Davis Cancer Center. Gleason scores ranged from 4 to 9 (29% of the patients had a Gleason score > or =8). The seminal vesicles were involved in three (21%) cases and the surgical margins were involved in seven (50%) cases. PSA values ranged from 0.3 to 6.7 (median: 0.7) ng/ml at the start of radiotherapy. Daily 1.8-2.0-Gy fractions were administered to total doses at isocenter ranging from 60.6 to 74.2 (median: 64.9) Gy. None of the patients received hormonal therapy. Follow-up ranged from 13 to 36 (median: 22) months. For patients with a preradiotherapy Hybritech PSA < or = 1.0 ng/ml, the Kaplan-Meier estimate of the 2-year biochemical disease-free survival rate is 67%, whereas for patients with a preradiotherapy PSA more than 1.0 ng/ml, the 2-year biochemical disease-free survival rate is 20% (p = 0.17). Because of the small number of patients, the difference is not statistically significant. A positive microscopic margin had no impact on the results obtained with salvage radiotherapy. Only one of four patients with a poorly differentiated adenocarcinoma remains free of disease. Acute toxicity was mild and did not require medication (Radiation Therapy Oncology Group grade I): four (29%) patients experienced genitourinary morbidity and three (21%) patients experienced gastrointestinal morbidity. With regard to late toxicity, one (7%) patient developed a urethral stricture requiring dilatation (Radiation Therapy Oncology Group grade III). All five patients who were potent at the start of radiotherapy remain potent. Medicare's median reimbursement for salvage three-dimensional conformal radiotherapy in this study ($7,512 in 1999 U.S. dollars) is equivalent to its reimbursement for a 17-month course of goserelin hormonal therapy. Patients with prostate cancer who develop an undetectable followed by a rising PSA postprostatectomy should be referred for salvage treatment with radiotherapy when their PSA is still less than or equal to 1.0 ng/ml. Salvage three-dimensional conformal radiotherapy is well tolerated and is less expensive than more than 17 months of goserelin.     

The relevance of prostatectomy findings for brachytherapy selection in patients with localized prostate carcinoma

BACKGROUND: The efficacy of brachytherapy for patients with localized prostate carcinoma depends on adequate radiotherapeutic coverage of the primary tumor and its subclinical extraprostatic extensions. Predictive models based on pretherapy factors may be useful to estimate the likelihood for clinically relevant extraprostatic disease and may be incorporated into selection criteria for this procedure. METHODS: Multivariate logistic regression model building was performed using pretherapy factors in 2905 surgically staged patients with localized prostate carcinoma to estimate the probability of seminal vesicle and/or lymph node involvement. Bootstrap methods were employed to assess the stability of the final model parameters and to determine the sensitivity and specificity of the final model. RESULTS: Clinical tumor classification, biopsy Gleason score groupings, and serum prostate specific antigen (PSA) levels were associated with seminal vesicle and/or pelvic lymph node involvement. These factors were incorporated into a multivariate model that predicted for these adverse histopathologic features. Allowing for up to a 10% likelihood for seminal vesicle and/or pelvic lymph node involvement, patients with tumors classified as T1c-T2a, Gleason scores of 2-6, and PSA < or = 16 ng/mL; or with tumors classified as T1c-T2a, Gleason scores of 7-10, and PSA < or = 4 ng/mL; or with tumors classified as T2b-T2c, Gleason scores of 2-6, and PSA < or = 6 ng/mL would be potential candidates for brachytherapy alone. CONCLUSIONS: The predictive model presented may provide criteria whereby an adequately performed prostate brachytherapy procedure is expected to encompass the intraprostatic and adjacent extraprostatic disease. Prostate brachytherapy alone may be considered in these circumstances, whereas the addition of external beam radiotherapy may be reserved for patients with disease that is apt to extend beyond the brachytherapy target volume.     

Serum prostate-specific antigen in monitoring the response of carcinoma of the prostate to radiation therapy.

In order to assess the value of serum prostate-specific antigen (PSA) levels in the monitoring of patients with localized prostatic carcinoma undergoing radical radiation therapy, 146 previously untreated patients were entered into this study. Sixty to 70 Gy were administered to the prostate over 8 to 9 weeks. Serum PSA levels were measured prior to radiotherapy, every 3 months during the first year and every 6 months thereafter. Median follow-up was 28 months. Pretreatment PSA values exceeded 10 ng/ml in 62% (91/146). Initial PSA values were correlated with tumor size and Gleason score. Six months after completion of radiation therapy, PSA levels decreased as compared to initial value in 88.3% of the patients. It had fallen to 10 ng/ml or less in 54 (59%) out of the 91 patients with initial abnormal PSA levels. Patients whose initial PSA exceeded 50 ng/ml attained levels of 10 ng/ml or less in only 19% of the cases (6/32). Only 3 of the 55 patients (5.5%) with both initial and 6-month PSA values less than or equal to 10 ng/ml developed metastasis. Out of the 91 patients with initial PSA values over 10 ng/ml, 54 (59.6%) had a 6-month PSA level of 10 ng/ml or less, and only 4/54 (7.4%) relapsed. By contrast, 13 of the 37 patients (35.1%) with a 6-month PSA value persistently above 10 ng/ml relapsed. The 3-year relapse-free survival is 85.1% for patients with a 6-month PSA level less than or equal to 10 ng/ml, and 50.2% for patients with persistently elevated PSA values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostate-specific antigen spikes after permanent prostate brachytherapy

PURPOSE: To evaluate whether any clinical, treatment, or dosimetric parameters correlated with the development of a prostate-specific antigen (PSA) spike after permanent prostate brachytherapy. METHODS AND MATERIALS: The evaluated population consisted of 218 hormone-naive patients free of biochemical or clinical failure who underwent permanent prostate brachytherapy with or without supplemental external beam radiotherapy for clinical Stage T1b-T3a adenocarcinoma of the prostate gland (1997 AJCC) between August 1995 and November 1999. No patient underwent pre- or postimplant hormonal manipulation, pretreatment seminal vesicle biopsy, or pathologic lymph node staging. In addition, none of the 218 patients possessed equivocal biochemical results (one or two consecutive PSA rises or a declining PSA >1.0 ng/mL). The median patient follow-up was 46.2 months. A PSA spike was defined as a rise of >or=0.2 ng/mL, followed by a durable decline. The clinical parameters evaluated included patient age, clinical T stage, Gleason score, pretreatment PSA level, prostate volume, brachytherapy planning volume, and patient follow-up in months. The evaluated treatment parameters included isotope and use of supplemental external beam radiotherapy. The dosimetric parameters evaluated included the minimal dose received by 90% of the prostate gland (D(90)), the percentage of the prostate volume receiving 100% (V(100)), 150%, and 200% (V(200)) of the prescribed minimal peripheral dose, and the mean, median, maximal, and minimal urethral doses. Biochemical disease-free survival was defined by the American Society for Therapeutic Radiology and Oncology consensus definition with the additional constraint that the most recent PSA level was 0.2 to 0.5 to 1.0 ng/mL (20%, 50%, and 80%, respectively, p <0.001). In Cox multivariate regression analysis, patient age, clinical stage, first postimplant PSA level, and V(150) were predictive for the development of a PSA spike. A postimplant dosimetric threshold of either <115% of the minimal peripheral dose for D(90) or <55% of the prostate volume for V(150) was strongly predictive of a spike. When the variables only determinable after the occurrence of the PSA spike were included in the multivariate analysis, V(150), preimplant PSA level, and nadir PSA were the significant predictors. CONCLUSION: Of the patients, 23.9% developed a PSA spike with a median time to development of 16.3 months and a median prespike and median postspike PSA of 0.50 ng/mL and 0.90 ng/mL, respectively. In multivariate analysis, patient age, clinical stage, first postimplant PSA level, and V(150) were predictive for the development of a PSA spike. At approximately 66 months after implantation, the PSA curves converged for spike and nonspike patients, with a median PSA level <0.1 ng/mL.     

Permanent interstitial brachytherapy for clinically organ-confined high-grade prostate cancer with a pretreatment PSA < 20 ng/mL

The objective of this study was to determine the effect of biopsy Gleason score 8 and 9 histology on biochemical outcome following a permanent prostate brachytherapy approach that includes multiple periprostatic seeds and supplemental external beam radiation. Forty-six consecutive T1c-T2b (1997 AJCC) patients with Gleason score 8 and 9 prostate cancer who were either hormone naive (33 patients) or received cytoreductive (< or =6 months) hormonal therapy (13 patients) underwent brachytherapy from June 1995 to November 2000. The median patient age was 69.7 years, with a median pretreatment prostate-specific antigen (PSA) of 7.7 ng/mL. The median follow-up was 58 months (range 27-93 months). Forty-five of the patients were implanted with Pd-103 and 44 received supplemental external beam radiation therapy (45 Gy). Biochemical success was defined by either a PSA < or = 0.4 ng/mL after a nadir or by the ASTRO consensus definition. The actuarial 7-year biochemical disease-free survival was 84.8% using either a PSA < or = 0.4 ng/mL or the ASTRO consensus definition. The median postimplant PSA was less than 0.1 ng/mL for both the hormone naive and hormonally manipulated patients. The utilization of hormonal therapy for 6 months or less duration resulted in a statistically nonsignificant improvement in biochemical outcome (92.3% versus 81.8%, P = 0.393). When stratified by pretreatment PSA, 87.9% of patients with a pretreatment PSA < or = 10 ng/mL and 76.9% with a pretreatment PSA > 10 ng/mL (P = 0.377) remained biochemically free of disease. In multivariate analysis, none of the clinical, treatment, or dosimetric parameters predicted for outcome. Following a permanent prostate brachytherapy approach that used multiple periprostatic seeds, the majority of patients with clinically organ-confined Gleason score 8 and 9 prostate cancer remain biochemically free of disease with identical outcomes for both biochemical definitions of success.     

Biochemical outcomes after prostate brachytherapy with 5-year minimal follow-up: importance of patient selection and implant quality

PURPOSE: A prostate brachytherapy program was initiated in 1990, when comparatively little was known of the relative importance of disease- and treatment-related factors on outcome. Patients treated during the first 6 years of the program were analyzed to determine the value of patient selection and implant quality on biochemical control. METHODS AND MATERIALS: We treated 243 patients with clinically localized prostate cancer with radioactive seed implantation and underwent 1-month CT-based dosimetric analysis. Follow-up ranged from 61 to 135 months (median 75). The Gleason score was < or =6 in 78% (n = 189), 7 in 14% (n = 35), and 8-10 in 8% (n = 19). The initial prostate-specific antigen (PSA) level was < or =10 ng/mL in 61% (n = 149), 10.1-20 ng/mL in 26% (n = 63), and >20 ng/mL in 13% (n = 31). The disease stage was T2a or less in 49% (n = 120), and Stage T2b-T2c in 51% (n = 123). A real-time ultrasound-guided technique was used with (125)I (n = 138) and (103)Pd (n = 105) isotopes. No patient underwent external beam radiotherapy as part of their primary treatment. Of the 243 patients, 60% also received hormonal ablation for at least 3 months before and 2-3 months after seed implantation. All patients included underwent a 1-month CT-based dosimetric analysis. The implant dose was defined as the dose delivered to 90% of the prostate volume on postimplant dosimetry (D(90)). On the basis of prior dose-response analyses, patients were retrospectively grouped into optimal D(90) ((125)I > or =140 Gy Task Group 43 or (103)Pd >/=100 Gy) and suboptimal D(90) ( (125)I <140 Gy or (103)Pd <100 Gy) dose groups. Biochemical failure was defined using the American Society for Therapeutic Radiology Oncology definition. RESULTS: Disease-related factors, including initial PSA level, Gleason score, and stage, were significant predictors of biochemical failure. The actuarial 8-year freedom from biochemical failure (bFFF) rate was 80% for those with a PSA level < or =10 ng/mL, 86% for PSA 10.1-20 ng/mL, and 45% for PSA >20 ng/mL (p = 0.0019). Patients with a Gleason score of < or =6 had an 8-year bFFF rate of 81% vs. 67% for those with Gleason score 7 and 53% for those with Gleason score 8-10 (p = 0.0003). Patients with Stage T2a or less had an 8-year bFFF rate of 85% compared with 69% for those with Stage T2b-T2c (p = 0.013). The 8-year bFFF rate was 88% for low-risk patients (Stage T2a or less, Gleason score < or =6, and initial PSA level < or =10 ng/mL; n = 75), 81% for moderate-risk patients (Stage T2b or Gleason score 7 or initial PSA level >10.1-20 ng/mL; n = 70), and 65% for high-risk patients (two or more moderate-risk features or Gleason score > or =8 or initial PSA level >20 ng/mL; n = 98; p = 0.0009). Patients with optimal dose implants (n = 145) had an 8-year bFFF rate of 82% compared with 68% for those with suboptimal dose implants (n = 98; p = 0.007). Hormonal therapy did not significantly affect biochemical failure (p = 0.27). In multivariate analysis, the statistically significant variables included initial PSA level (p <0.0001), Gleason score (p = 0.024), and dose group (p = 0.046). Because our current practice limits implantation alone to low-risk patients, an analysis of this subgroup was undertaken to validate the importance of dose. In the optimal dose group, low-risk patients had an 8-year bFFF rate of 94% vs. 75% for the low-risk patients in the suboptimal dose group (p = 0.02). CONCLUSION: With minimal follow-up of 5 years, these data continue to support the use of implantation alone in low-risk prostate cancer patients and demonstrate the importance of implant quality (dose) in achieving optimal outcomes. Low-risk patients who receive an optimal dose implant have a 94% bFFF rate at 8 years.     

Actuarial disease-free survival after prostate cancer brachytherapy using interactive techniques with biplane ultrasound and fluoroscopic guidance

Purpose: To evaluate the effectiveness and safety of interactive transperineal brachytherapy under biplane ultrasound and fluoroscopic guidance in patients with localized prostate cancer.Methods and Materials: Brachytherapy using ¹²⁵I or ¹⁰³Pd radioactive seeds either alone or in combination with adjunctive external beam radiotherapy (XRT) was administered to 490 patients at a single institution. Post-treatment follow-up included clinical assessment of disease status, assays of serum prostate-specific antigen (PSA) levels and documentation of treatment-related symptoms and complications.Results: Actuarial disease-free survival at 5 yr was 79% (95% CI, 71–85%), and the 5-yr actuarial rate of local control was 98% (95% CI, 94–99%). Post-treatment PSA nadir and pretreatment PSA level were found to be significant predictors of disease-free survival. In patients with a PSA nadir < 0.5 ng/ml, 5-yr disease-free survival was 93% (95% CI, 84–97%), compared with 25% (95% CI, 5–53%) in patients whose PSA nadir was 0.5–1.0 ng/ml and 15% (95% CI, 3–38) in patients with a PSA nadir > 1.0 ng/ml. Brachytherapy was well tolerated with few post-treatment complications.Conclusion: A broad range of patients with localized prostate cancer can benefit from transperineal brachytherapy with minimal morbidity. A post-treatment PSA nadir below 0.5 ng/ml provides a useful prognostic indicator of favorable long-term outcome.     

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.     

Combined 3-dimensional conformal radiotherapy and transperineal Pd-103 permanent implantation for patients with intermediate and unfavorable risk prostate cancer

PURPOSE: To evaluate the efficacy and morbidity of combined 3-dimensional conformal radiation therapy (3D-CRT) and brachytherapy for intermediate/unfavorable risk prostate cancer. MATERIALS AND METHODS: Between May 1996 and November 1997, 65 patients with intermediate/unfavorable risk prostate cancer were treated with 3D-CRT (50.4 Gy) followed by a transperineal permanent Pd-103 implant. Patients with one or two adverse prognostic features (PSA > 10 and Gleason > or = 7) were classified as intermediate risk and unfavorable risk, respectively. Forty-seven patients (71%) had intermediate risk and 18 (29%) had unfavorable disease risk. The median age of this group was 65 years (range, 42-76 years), and the median pretreatment PSA level was 8.0 ng/ml (range, 1.7-42.0 ng/ml). The clinical stage of these patients was as follows: Tlc, 36 (55%); T2a, 27 (42%); T2b/T3, 2 (3%). Fifteen patients (23%) had a Gleason < or = 6, 41 patients (63%) were classified as Gleason 7, and 9 (14%) as Gleason > or = 8. Fifty-two (80%) received neoadjuvant androgen deprivation (NAAD) for cytoreduction. The median follow-up was 36 months (range, 24-42 months). RESULTS: The PSA relapse-free survival rate at 3 years was 87%, with a median PSA value at last follow-up of 0.25 ng/ml. The relapse-free survival was 90% for those who had an initial PSA < or = 10 ng/ml and 80% for patients who had an initial PSA > 10 ng/ml (p = 0.5). No difference in outcome was observed between patients with intermediate and unfavorable risk disease. Eight patients (13%) developed late Grade 2 rectal bleeding. Twenty-three patients (42%) required medication for urinary symptoms during the first 6 months after therapy. Three patients (5 %) noted rare stress incontinence at last follow-up. Of the 44 patients who were potent prior to therapy, 17 (26%) developed erectile dysfunction (ED). CONCLUSION: Although the follow-up is short, the early biochemical outcome of combined 3D-CRT and brachytherapy for intermediate/unfavorable risk prostate cancer is promising. While rectal toxicity is minimal, urinary side effects are more common. Further follow-up is necessary to fully evaluate the efficacy of this combined therapeutic approach.     

Four-year biochemical outcome after radioimmunoguided transperineal brachytherapy for patients with prostate adenocarcinoma

PURPOSE: To evaluate 4-year biochemical outcomes for patients with prostate adenocarcinoma who underwent radioimmunoguided (Prostascint) permanent prostate brachytherapy. METHODS AND MATERIALS: Eighty patients with clinical T1C-T3A NxM0 prostate cancer underwent ProstaScint-guided prostate brachytherapy using either (103)Pd or (125)I between February 1997 and December 2000. Sixty-seven patients underwent prostate brachytherapy alone, whereas 13 patients received neoadjuvant hormonal manipulation before implantation. Risk factors (RF) included PSA >10, Stage >or=T2b, and Gleason grade >or=7. Sixty patients had low-risk disease (0 RF), 17 were intermediate risk (1 RF), and 3 were high risk (2 RF). Biochemical disease-free survival (bDFS) was calculated using the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria, a PSA cutoff of 1.0 ng/mL, and a PSA cutoff of 0.5 ng/mL. RESULTS: Four-year bDFS for the entire cohort was 97.4% using the ASTRO consensus criteria. Low-risk patients (60) had a 4-year bDFS of 100%; intermediate- and high-risk patients (20 patients) were 89.2%. The hormonally na?ve group (67 patients) had a 4-year bDFS of 96.9% and a median PSA nadir of 0.2 ng/mL. Median time to nadir was 19.8 months (range: 1.9-53.2 months). For the neoadjuvant hormonal therapy group (13 patients), ASTRO-defined bDFS was 100%. Overall, 85.2% of patients had a posttreatment PSA 相似文献   

Failure-free survival following brachytherapy alone or external beam irradiation alone for T1-2 prostate tumors in 2222 patients: results from a single practice

PURPOSE: To evaluate failure-free survival (FFS) for brachytherapy (BT) alone compared to external beam radiotherapy (EBRT) alone for Stage T1-2 Nx-No Mo patients over the same time period by a single community-based practice in the prostate-specific antigen (PSA) era. MATERIALS AND METHODS: The database of Arizona Oncology Services (a multiphysician radiation oncology practice in the Phoenix metropolitan area) was reviewed for patients meeting the following criteria: (1) T1 or T2 Nx-No Mo prostate cancer; (2) no prior or concurrent therapy including hormones; (3) treatment period 12/88-12/95; and (4) treatment with either EBRT alone or BT alone ((125)I or (103)Pd). This yielded 1527 EBRT and 695 BT patients; no patients meeting the above criteria were excluded from analysis. Median follow-up for EBRT patients was 41.3 months and, for BT patients, 51.3 months. Patients were not randomized to either therapy but rather received EBRT or BT based upon patient, treating, and/or referring physician preference. PSA failure was defined according to the ASTRO consensus guidelines. The median patient age was 74 years for both groups. RESULTS: Failure-free survival at 5 years for EBRT and BT are 69% and 71%, respectively (p = 0.91). For T stage, no significant difference in FFS at 5 years is observed between EBRT and BT for either T1 (78% vs. 83%, p = 0.47) or T2 (67% vs. 67%, p = 0.89) tumors. Analysis by Gleason score shows superior outcomes for Gleason 8-10 lesions treated with EBRT vs. BT (5-year FFS 52% vs. 28%, p = 0.04); outcomes for lower grade lesions (Gleason 4-6) when analyzed by Gleason score alone do not significantly differ according to treatment received. Patients with initial PSA values of 10-20 ng/dL have an improved FFS with EBRT vs. BT at 5 years (70% vs. 53%, p = 0.001); outcomes for patients with initial PSA ranges of 0-4 ng/dL, of > 4-10 ng/dL, and > 20 ng/dL did not differ significantly by treatment received. FFS was also determined for presenting Gleason score/PSA combinations; all Gleason combinations in the initial PSA range >10-20 ng/dL had superior outcomes with EBRT compared to BT, and this reached statistical significance for Gleason scores of 2-4 (72% vs. 58%, p = 0.026), Gleason 7 (67% vs. 28%, p = 0.002), and Gleason 8-10 (63% vs. 23%, p = 0.05). CONCLUSION: In our patient population, either EBRT or BT appear equally efficacious for patients with T1/T2 disease with Gleason scores 10 ng/dL (but 20 ng/dL, as would be anticipated from the significant risks of occult distant metastasis in this group. To our knowledge, this is the first report comparing the outcome of EBRT and BT treatment in patients treated concurrently by a single group, and these results, achieved in a community-based practice, compare favorably to data from academic centers regarding external beam, brachytherapy, or surgical outcomes and should be generalizable to the community at large.     

Radical prostatectomy for prostate cancer patients with prostate-specific antigen >20 ng/ml

OBJECTIVE: Prostate cancer patients with prostate-specific antigen (PSA) >20 ng/ml are at high risk of progression after radical prostatectomy. Comparison has seldom been made between the outcomes of patients with PSA 20.1-50 ng/ml and those with PSA >50 ng/ml after radical prostatectomy. We retrospectively analyzed the outcomes of these two groups. METHODS: From 1993 to 2002, 60 prostate cancer patients receiving radical prostatectomy were enrolled in this study. Thirty-seven patients with PSA 20.1-50 ng/ml were assigned to Group I. Twenty-three patients with PSA >50 ng/ml were assigned to Group II. Preoperatively, Group II had greater PSA and PSA density than Group I (P < 0.0001). Group II had higher biopsy Gleason score and clinical stage than Group I (P < 0.05). Pathological categories and outcomes of both groups were compared. RESULTS: Group II had higher Gleason score and tumor volume than Group I (P < 0.05). The incidence of organ-confined diseases was 29.7% in Group I and 0% in Group II (P < 0.05). Group II had higher incidence of extracapsular tumor extension, positive surgical margin and lymph node involvement than Group I (P < 0.05). The incidence of postoperative PSA >0.01 ng/ml and PSA failure were higher in Group II than Group I (P < 0.05). Need for adjuvant treatment and death from prostate cancer was similar in both groups. CONCLUSION: Patients with PSA >50 ng/ml had a poorer prognosis than patients with PSA 20.1-50 ng/ml. Those with PSA >50 ng/ml had shorter freedom from PSA failure survivals than those with PSA 20.1-50 ng/ml (P = 0.004). Classification of high-risk prostate patients into two sub-groups with PSA 20.1-50 ng/ml and PSA >50 ng/ml should be considered.     

PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer: a multi-institutional analysis

PURPOSE: To determine the significance of prostate-specific antigen (PSA) nadir (nPSA) and the time to nPSA (T(nPSA)) in predicting biochemical or clinical disease-free survival (PSA-DFS) and distant metastasis-free survival (DMFS) in patients treated with definitive external beam radiotherapy (RT) for clinical Stage T1b-T2 prostate cancer. METHODS AND MATERIALS: Nine participating institutions submitted data on 4839 patients treated between 1986 and 1995 for Stage T1b-T2cN0-NxM0 prostate cancer. All patients were treated definitively with RT alone to doses > or =60 Gy, without neoadjuvant or planned adjuvant androgen suppression. A total of 4833 patients with a median follow-up of 6.3 years met the criteria for analysis. Two endpoints were considered: (1) PSA-DFS, defined as freedom from PSA failure (American Society for Therapeutic Radiology and Oncology definition), initiation of androgen suppression after completion of RT, or documented local or distant failure; and (2) DMFS, defined as freedom from clinically apparent distant failure. In patients with failure, nPSA was defined as the lowest PSA measurement before any failure. In patients without failure, nPSA was the lowest PSA measurement during the entire follow-up period. T(nPSA) was calculated from the completion of RT to the nPSA date. Results: A greater nPSA level and shorter T(nPSA) were associated with decreased PSA-DFS and DMFS in all patients and in all risk categories (low [Stage T1b, T1c, or T2a, Gleason score < or =6, and PSA level < or =10 ng/mL], intermediate [Stage T1b, T1c, or T2a, Gleason score < or =6, and PSA level >10 but < or =20 ng/mL, or Stage T2b or T2c, Gleason score < or =6, and PSA level < or =20 ng/mL, or Gleason score 7 and PSA level < or =20 ng/mL], and high [Gleason score 8-10 or PSA level >20 ng/mL]), regardless of RT dose. The 8-year PSA-DFS and DMFS rate for patients with nPSA <0.5 ng/mL was 75% and 97%; nPSA > or =0.5 but <1.0 ng/mL, 52% and 96%; nPSA > or =1.0 but <2.0 ng/mL, 40% and 91%; and nPSA > or =2.0 ng/mL, 17% and 73%, respectively. The 8-year PSA-DFS and DMFS rate for patients with T(nPSA) <6 months was 27% and 66%; T(nPSA) > or =6 but <12 months, 31% and 85%; T(nPSA) > or =12 but <24 months, 42% and 94%; and T(nPSA) > or =24 months, 75% and 99%, respectively. A shorter T(nPSA) was associated with decreased PSA-DFS and DMFS, regardless of the nPSA. Both nPSA and T(nPSA) were significant predictors of PSA-DFS and DMFS in multivariate models incorporating clinical stage, Gleason score, initial PSA level, and RT dose. The significance of nPSA and T(nPSA) was supported by landmark analysis, as well as by analysis of nPSA and T(nPSA) as time-dependent covariates. A dose > or =70 Gy was associated with a lower nPSA level and longer T(nPSA) in all risk categories, and a greater dose was significantly associated with greater PSA-DFS and DMFS in multivariate analysis. Regression analysis confirmed that higher clinical stage, Gleason score, and initial PSA were associated with a greater nPSA level. Conclusion: The results of this large, multi-institutional analysis of 4833 patients have provided important evidence that nPSA and T(nPSA) after definitive external beam RT are not only predictive of a predominantly PSA endpoint (PSA-DFS), but are also predictive of distant metastasis in all clinical risk categories. Greater RT doses were associated with lower nPSA, longer T(nPSA), and improved PSA-DFS and DMFS.     

Analysis of prostate-specific antigen bounce after I permanent seed implant for localised prostate cancer

BACKGROUND AND PURPOSE: To report on the incidence of benign prostate-specific antigen bounce following permanent I(125) prostate brachytherapy, to describe the associations in our population and review the relationship of bounce to subsequent biochemical failure. MATERIALS AND METHODS: From February 2000 to May 2005, 374 patients with localised prostate cancer were treated with I(125) permanent prostate brachytherapy at a single institution. A prospectively collected database was used to identify cases of prostate-specific antigen (PSA) bounce, defined as a rise of 0.2 ng/ml above an initial PSA nadir with subsequent decline to or below that nadir without treatment. The patients who received neo-adjuvant or adjuvant hormone manipulation were excluded. Biochemical failure was determined using the both the ASTRO consensus definition and Phoenix (nadir +2 ng/mL) definition. RESULTS: Two hundred and five patients were identified with a median follow-up of 45 months (24-85). PSA bounce was noted in 79 (37%) men, occurring at a median of 14.8 months (1.7-40.6) following implant. The median peak PSA was 1.8 ng/ml (0.4-7.4) with a bounce magnitude of 0.91 ng/ml (0.2-5.8). When pre- and post-implant factors were assessed for association to bounce, only younger age was statistically significant (p=0.002). The threshold for biochemical failure as defined by the ASTRO consensus definition (1997) was met in 4 (5%) patients after experiencing bounce as opposed to 19 (15%) non-bounce patients (p=0.01). The threshold for Phoenix (nadir +2 ng/mL) was met in 6 (7.5%) patients following bounce versus 22 (17%) of non-bounce patients (p=0.003). Both definitions are prone to false positive calls during bounce. Median PSA velocity during the bounce was 0.08 ng/mL/month (0.02-0.98) and was statistically significantly lower than the median velocity prior to the Phoenix biochemical failure at 0.28 ng/mL/month (0.07-2.04) (p=0.0005). CONCLUSION: PSA bounce is a common finding in our population and is associated with a lower rate of subsequent biochemical failure. The noted differences in PSA velocity will require verification in a future analysis to reduce the influence of median follow-up on this finding. Patients should be advised of the potential of bounce in PSA follow-up after permanent I(125) prostate brachytherapy and physicians involved in follow-up of prostate brachytherapy patients should be aware of this phenomenon, allowing them to commit to appropriate PSA surveillance, avoiding the premature and inappropriate initiation of salvage therapy during PSA bounce.     

Failure free survival following brachytherapy alone for prostate cancer: comparison with external beam radiotherapy.

BACKGROUND AND PURPOSE: To compare failure free survival (FFS) for brachytherapy (BT) alone and external beam radiotherapy (EBXRT) alone. MATERIALS AND METHODS: Between 12/88 and 12/95, 1527 and 695 T(1) or T(2) Nx-No Mo prostate cancer patients (from the Arizona Oncology Services database) were treated with either EBXRT or BT, respectively. The median age was 74 years. Median follow-up for EBXRT and BT patients was 41.3 and 51.3 months, respectively. RESULTS: Overall FFS at 5 years for EBXRT and BT were 69 and 71%, respectively (P=0.91). No significant difference in FFS at 5 years was observed between EBXRT and BT for either T(1) (78 vs. 83%, P=0.47) or T(2) (67 vs. 67%, P=0.89) tumours. Superior outcomes for Gleason 8-10 lesions treated with EBXRT vs. BT (5 years FFS 52 vs. 28%, P=0.04) were observed; outcomes for lower grade lesions when analysed by Gleason score alone did not significantly differ according to treatment received. Patients with initial PSA values 10-20 ng/dl had an improved FFS with EBXRT vs. BT (70 vs. 53%, P=0.001); outcomes for patients with initial PSA ranges 0-4 ng/dl, >4-10 ng/dl and >20 ng/dl did not differ significantly with treatment received. CONCLUSIONS: EBXRT and BT appear to be equally efficacious for low-risk patients having T(1)/T(2) disease with Gleason scores <6 and PSA <10 ng/dl. Patients with Gleason scores 8-10 or PSA >10 ng/dl-<20 ng/dl) appear to fare worse with BT alone compared with EBXRT. Neither EBXRT nor BT were particularly effective for patients with a presenting PSA >20 ng/dl.     

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.