Treatment of localized prostate cancer using high-intensity focused ultrasound

OBJECTIVE: To evaluate the biochemical disease-free survival (DFS), predictors of clinical outcome and morbidity of patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU), a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin. PATIENTS AND METHODS: In all, 63 patients with stage T1c-2bN0M0 localized prostate cancer underwent HIFU using the Sonablate system (Focus Surgery, Inc., Indianapolis, IN, USA). None of the patients received neoadjuvant and/or adjuvant therapy. Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology consensus definition, i.e. three consecutive increases in prostate-specific antigen (PSA) level after the nadir. The median (range) age, PSA level and follow-up were 71 (45-87) years, 8.5 (3.39-57.0) ng/mL and 22.0 (3-63) months, respectively. RESULTS: The overall biochemical disease-free rate was 75% (47 patients). The 3-year biochemical DFS rates for patients with a PSA level before HIFU of <10, 10.01-20 and >20 ng/mL were 82%, 62% and 20% (P < 0.001), respectively. The 3-year biochemical DFS rates for patients with a PSA nadir of <0.2, 0.21-1 and >1 ng/mL were 100%, 74% and 21% (P < 0.001), respectively. Final follow-up sextant biopsies showed that 55 (87%) of the patients were cancer-free. Multivariate analysis showed that the PSA nadir (P < 0.001) was a significant independent predictor of relapse. CONCLUSION: HIFU therapy appears to be a safe, effective and minimally invasive therapy for patients with localized prostate cancer, and the PSA nadir is a useful predictor of clinical outcome.     

Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer

BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. METHODS: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). RESULTS: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.     

First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer

OBJECTIVE: To evaluate the long-term efficacy of high-intensity focused ultrasound (HIFU) therapy for patients with localised prostate cancer. MATERIAL AND METHODS: Patients included in this multicentre analysis had T1-T2 NxM0 prostate cancer, a PSA<15 ng/ml, and a Gleason score (GS) < or = 7, and were treated with prototypes or first-generation Ablatherm HIFU devices between October 1997 and August 2001. The Phoenix definition of biochemical failure was used (PSA nadir+2). Treatment failure was defined as: biochemical failure or positive biopsy. RESULTS: A total of 140 patients with a mean (SD) age 69.1 yr (6.6) were included. Mean (SD) follow-up was 6.4 yr (1.1). Control prostate biopsies were negative in 86.4% of patients. Median PSA nadir of 0.16 ng/ml (range, 0.0-9.1) was achieved at a mean (SD) of 4.9 mo (5.2). A PSA nadir < or = 0.5 ng/ml was recorded in 68.4% of patients. The actuarial biochemical failure-free survival rates (SR) at 5 and 7 yr were 77% and 69%, respectively. The actuarial disease-free SR at 5 and 7 yr were 66% and 59%, respectively. CONCLUSIONS: This study demonstrates the effective long-term cancer control achieved with HIFU in patients with low- or intermediate-risk localised prostate cancer.     

Control of prostate cancer by transrectal HIFU in 227 patients

PURPOSE: To evaluate the results of high-intensity focused ultrasound (HIFU) treatment of localized prostate cancer with reference to disease-related prognostic factors. MATERIALS AND METHODS: Patients with T1-2 localized prostate cancers, prostate specific antigen (PSA) 1 ng/ml with three consecutive rises. RESULTS: The study included 227 patients. Mean follow-up was 27+/-20 months (12-121 months). Eighty-six percent had negative control biopsies. Median nadir PSA was 0.10 ng/ml. The actuarial 5-year disease-free survival rate (DFSR), combining pathologic and biochemical outcomes, was 66%. DFSR showed a significant decrease when stratified according to initial PSA level: 90% with PSA 相似文献   

High-intensity focused ultrasound in prostate cancer; a systematic literature review of the French Association of Urology

We discuss the efficacy and safety of high-intensity focused ultrasound (HIFU) in patients with prostate cancer, to define the best indications for HIFU in daily clinical practice as primary therapy. We searched Medline and Embase for clinical studies evaluating the efficacy and safety of HIFU in prostate cancer (July 2007), and abstracts presented at the 2005-2007 annual meetings of the European Association of Urology and American Urological Association were screened. In all, 37 articles/abstracts were selected. As the data on HIFU as salvage therapy were limited, we focused on HIFU as primary therapy. Studies consisted of case series only. Included patients were approximately 70 years old with T1-T2 N0M0 disease, Gleason Score or=70 years) with T1-T2 N0M0 disease, a Gleason score of <7, a PSA level of <15 ng/mL and a prostate volume of <40 mL. In these patients HIFU achieves short-term cancer control, as shown by a high percentage of negative biopsies and significantly reduced PSA levels. The median-term survival data also seem promising, but long-term follow-up studies are needed to further evaluate cancer-specific and overall survival rates before the indications for primary therapy can be expanded.     

Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer

BACKGROUND AND PURPOSE: Criteria for determining the durability of the response to transrectal high-intensity focused ultrasound (HIFU) ablation of prostate cancer have been established by calculating progression-free probability. PATIENTS AND METHODS: A series of 82 patients (mean age 71 +/- 5.7 years) with biopsy-proven localized (stage T1-T2) cancer who were not suitable candidates for radical surgery underwent transfectal HIFU ablation with the Ablatherm machine. The mean follow-up was 17.6 months (range 3-68 months). The mean serum prostate specific antigen (PSA) value and mean prostate volume were 8.11 +/- 4.64 ng/mL and 34.9 +/- 17.4 cm3, respectively. Progression was rigidly defined as any positive biopsy result, regardless of PSA concentration, or three successive PSA increases for patients with a negative biopsy (PSA velocity > or = 0.75). Times to specific events (positive biopsy and PSA elevation) were analyzed with the Kaplan-Meier survival method. RESULTS: Overall, 62% of the patients exhibited no evidence of disease progression 60 months after transrectal HIFU ablation. In particular, the disease-free rate was 68% for the moderate-risk group of 50 patients (PSA < 15.0 ng/mL, Gleason sum < 8, prostate volume < 40 cm3, and number of positive biopsies < 5). For the low-risk group of 32 patients (PSA < 10 ng/mL and Gleason sum < 7), the disease-free survival rate was 83%. CONCLUSION: Transrectal HIFU prostate ablation is an effective therapeutic alternative for patients with localized prostatic adenocarcinoma.     

PSA nadir is a significant predictor of treatment failure after high-intensity focussed ultrasound (HIFU) treatment of localised prostate cancer

OBJECTIVES: To assess if prostate-specific antigen (PSA) nadir is an independent predictor of treatment failure and disease-free survival after high-intensity focussed ultrasound (HIFU) therapy for localised prostate cancer as defined by the new ASTRO criteria. METHODS: One hundred three patients after HIFU treatment (Ablatherm, EDAP, Lyon, France) for localised prostate cancer without previous hormonal therapy were evaluated retrospectively. Patients attended regular follow-up visits every 3 mo. Treatment failure was defined by the revised ASTRO criteria (PSA >or=2 ng/ml above nadir PSA, positive biopsy, if salvage treatment was administered). Patients were divided into three PSA nadir subgroups (group 1, 1 ng/ml). The disease-free survival rate (DFSR) was calculated by using life table methods. The log-rank test was used to compare the curves based on Kaplan-Meier models. RESULTS: The median follow-up was 4.9 (3-8.6) yr. Mean time to PSA nadir was 6.4+/-5.1 mo. A PSA nadir of 1ng/ml was reached by 64%, 22.3%, and 13.6% of patients, respectively. Treatment failure rates during follow-up were 4.5%, 30.4%, and 100%, respectively, for the three groups (p<0.001). The actuarial DFSRs at 5 yr were 95%, 55%, and 0%, respectively, for the 3 groups (p<0.001). CONCLUSIONS: The PSA nadir after HIFU correlates highly significantly with treatment failure and DFSR, and can be applied in daily clinical practice. Promising oncological outcome is obtained if a PSA nadir of 相似文献   

Prostate specific antigen nadir following external beam radiation therapy for clinically localized prostate Cancer: The relationship between nadir level and disease-free survival

Purpose

We determined whether the prostate specific antigen (PSA) nadir achieved following external beam radiation therapy alone predicts biochemical disease-free survival in a large cohort of men with clinically localized prostate cancer.

Materials and Methods

Between January 1986 and October 1993, 364 men with clinically localized, stages T1 to T3 adenocarcinoma of the prostate received definitive external beam radiation therapy with no prior, concomitant or adjuvant endocrine therapy. PSA was measured before treatment in 326 men (90 percent) and serial PSA was measured following treatment in all patients. All men were followed continuously for at least 24 months (median 44 months, range 24 to 90, mean 46). Biochemical failure after irradiation was defined as PSA of 1.5 ng./ml. or more and 2 consecutive serum PSA elevations.

Results

The 5-year overall biochemical disease-free survival rate for the entire group was 56 percent. PSA nadir was predictive of subsequent biochemical disease-free survival. The biochemical disease-free survival rate at 3 years was 93, 49 and 16 percent for PSA nadirs of 0 to 0.99, 1 to 1.99 and 2 or more ng./ml., respectively (p = 0.0001). In a multivariate analysis PSA nadir (0 to 0.99 versus 1.0 to 1.99 versus 2 or more ng./ml.) was an independent predictor of biochemical disease-free survival along with pretreatment PSA, central axis dose, Gleason grade and T stage.

Conclusions

PSA nadir after radiation therapy is an indicator of subsequent biochemical disease-free survival. Patients who achieve a nadir of less than 1 ng./ml. following external beam radiation therapy have a favorable biochemical disease-free survival rate, while those with a nadir of greater than 1 ng./ml. have a high subsequent failure rate. Strategies to improve results should focus on techniques to increase the likelihood of achieving a PSA nadir of less than 1 ng./ml.     

Impact of preoperative serum PSA level from 0 to 10 ng/ml on pathological findings and disease-free survival after radical prostatectomy

BACKGROUND: To determine the impact of various preoperative serum prostate specific antigen (PSA) levels in the range from 0.1 to 10 ng/ml on pathological stage and disease-free survival after radical prostatectomy. METHODS: We selected a cohort of 585 patients who underwent radical prostatectomy between 1991-1996 for clinically localized prostate cancer and presented with preoperative serum PSA levels from 0.1 to 10 ng/ml. RESULTS: Pathological organ-confined disease was present in 57.6% of patients. The rate of organ-confined disease decreased from an average of 85% for patients with a PSA value < 2 ng/ml, to 46.8% for patients with a PSA value > 7 ng/ml. We found statistically significant correlations between preoperative serum PSA level and overall pathological stage (P = 0.001), pathologically organ-confined disease (P = 0.001), margin positive rates (P = 0.001), extra prostatic extension (P = 0.001), and seminal vesicle invasion (P = 0.001). The overall disease-free survival rate was 87%, with a median follow up of 42.4 months. Disease free survival was significantly better for patients with PSA up to 4 ng/ml (P = 0.005). CONCLUSIONS: Our data suggests that PSA detection programs should strive to detect prostate cancer in men before the PSA level rises above 7 ng/ml. In addition, since patients with a PSA level < 4 ng/ml had better disease-free survival rates than those with a PSA level between 4.1-10 ng/ml, eliminating an arbitrary cutoff of 4 ng/ml, may lead to improved disease-free survival.     

A standard definition of disease freedom is needed for prostate cancer: undetectable prostate specific antigen compared with the American Society of Therapeutic Radiology and Oncology consensus definition

PURPOSE: Freedom from prostate cancer is defined by undetectable prostate specific antigen (PSA) after surgery and the American Society of Therapeutic Radiology and Oncology (ASTRO) criteria are recommended for irradiation. Whether these definitions of disease freedom are comparable was evaluated in this study. MATERIALS AND METHODS: From August 1992 to August 1996 simultaneous irradiation with prostate 125iodine implantation followed by external beam irradiation was performed in 591 consecutive men with stage T1T2NX prostate cancer. All patients had a transperineal implant and none received neoadjuvant hormones. Disease freedom was defined by a PSA cutoff of 0.2 ng./ml. and the ASTRO consensus definition. Median followup was 6 years (range 5 to 8). RESULTS: Of the 591 men in this study 65 had recurrence by ASTRO criteria and 93 had recurrence by a PSA cutoff of 0.2 ng./ml., which was a significant difference (p = 0.001). On multivariate analysis of the factors related to disease-free status the definition of disease freedom, pretreatment PSA and Gleason score were highly significant. Of the 528 men with a minimum 5-year PSA followup the 8-year disease-free survival rate by ASTRO criteria was 99% in those who achieved a PSA nadir of 0.2 ng./ml. and 16% in those with a nadir of 0.3 to 1 ng./ml. Of the 469 disease-free patients by ASTRO criteria with a minimum 5-year followup 455 (97%) achieved a PSA nadir of 0.2 ng./ml. or less. CONCLUSIONS: The definition of freedom from prostate cancer significantly affects treatment results. A standard definition is needed and a PSA cutoff of 0.2 ng./ml. is suggested as the standard for all curative treatments for localized prostate cancer.     

8-month neoadjuvant hormonal therapy before radical prostatectomy for high-risk prostate cancer

PURPOSE: To evaluate the clinicopathological outcomes of 8 months of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy for high-risk prostate cancer. PATIENTS AND METHODS: A multi-institutional prospective trial was performed between July 2000 and May 2003 involving high-risk prostate cancer patients without metastasis, including 21 who received 8 months of NHT before radical prostatectomy. High-risk group was defined as clinical stage > or =T2c and/or prostate-specific antigen (PSA) >20 ng/ml and/or Gleason score > or =8. PSA values were considered elevated (biochemical failure) if values of 0.1 ng/ml or greater were obtained. RESULTS: Median of initial PSA levels before prostate biopsy was 27.6 ng/ml (8.5-80.7 ng/ml), and median of pre-operative PSA levels after NHT was 0.28 ng/ml (0.02-4.2 ng/ml). There were 5 patients (23.8%) with lower limit of PSA detection (less than 0.02 ng/ml) in 8 months after NHT. The clinical T stage was T1c in 9 patients (42.9%), T2a-b in 8 patients (38.1%), T2c in 3 patients (14.3%), and T3a in 1 patient (4.8%). The median follow-up was 25 months (range 4 to 37). There were 2 patients (9.5%) in pT0, 5 patients (23.8%) with positive surgical margin, 5 patients (23.8%) with extracapsular extension (ECE) and 3 patients (14.3%) with seminal vesicle involvement (SVI). Biochemical failure was occurred in 9 of 21 (42.9%) including of one pT0. Range of time to postoperative biochemical failure was 2 to 25 months (median 6 months) and most of biochemical failure was found within 12 months after surgery. Biochemical failure rate was significantly higher in patient with positive SVI (p = 0.0308) and higher in patients with pre-operative PSA levels of more than 0.1 ng/ml (p = 0.0836), positive ECE (p = 0.0545) and positive surgical margin (p = 0.0545). CONCLUSION: Biochemical failure was frequent after this combined treatment, even in a pT0 case. Long-term follow-up of patients is needed to assess the impact of this therapy on mortality.     

Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome

OBJECTIVES: Efficacy evaluation of high intensity focused ultrasound (HIFU) treatment for localized prostate cancer and identification of the factors affecting the outcome. PATIENTS AND METHODS: 102 patients with prostate cancer stage T1-T2 and noncandidates for radical prostatectomy have been treated with HIFU (Ablatherm, EDAP-Technomed). The disease progression (failure) was strictly defined by any positive sample at control biopsies, whatever the prostate-specific antigen (PSA) level, or by 3 consecutive increases in PSA levels in case of negative biopsies. RESULTS: At inclusion, patients' baseline characteristics were (mean +/- standard deviation): age 70.8 (+/-6.13) years, PSA 8.38 (+/-4.8) ng/ml, prostate volume 33.3 (+/-16.71) cm3. The population mean follow-up was 19 months (3-76 months). The overall success rate was 66%. Statistically significant variations of the overall success with a more favorable outcome were observed when (1) the initial PSA level was < or =10 ng/ml (73 vs. 50%, p = 0.02), (2) the Gleason score was < or =6 (81 vs. 46%, p<0.001) and (3) the pretreatment sextant biopsy evidenced 1-4 positive samples (68 vs. 40%, p = 0.01). CONCLUSION: Results observed after HIFU treatment in localized prostate cancer are now challenging those obtained after radiation therapy. The success rate is influenced by disease-related prognostic factors.     

PSA bouncing after external beam radiation for prostate cancer with or without hormonal treatment

OBJECTIVES: The purpose of this study was to find out the frequency of PSA bouncing and the factors effecting PSA bounce after external beam radiation treatment (EBRT) with or without hormonal treatment (HT) for prostate cancer and to identify any possible relationship with biochemical control. METHODS: Between March 1997 and November 2000, 72 consecutive patients with clinically localised prostate cancer were treated by EBRT with or without HT. All patients had a pretreatment PSA level, at least six post-treatment PSA levels and minimum two years of follow-up. Median follow-up for all patients was 51 months (range 25-69 months). Median radiation dose given to the center of the prostate was 70Gy (range 63-74Gy). Fifty-nine patients (82%) received adjuvant HT with median duration of six months. PSA bounce was defined as a minimal rise of 0.4ng/ml over six months (monthly rise > or =0.07 ng/ml), followed by any decrease. Biochemical failure was defined in accordance with the ASTRO consensus guidelines. RESULTS: Seventeen patients (24%) experienced at least one PSA bounce. PSA bounces were more frequent in patients with T1-2 stage, pretreatment PSA <10 ng/ml, small field irradiation, radiation dose < or =70 Gy, PSA nadir > or =0.2 ng/ml and without HT. PSA bounce occurred in 54% of patients treated by EBRT only, and 17% of patients treated by EBRT and HT. Logistic regression model for multivariate analysis revealed the radiation field size as the only independent predictive factor for PSA bounce. Five-year biochemical control rates were 82% for non-bouncers and 88% for bouncers (p=0.5). CONCLUSIONS: PSA bouncing occurs in approximately a quarter of patients treated with EBRT with or without HT. It is associated with pretreatment and treatment characteristics, but we did not observe any relationship with biochemical failure.     

High-intensity focused ultrasound therapy for clinically localized prostate cancer

The efficacy of high-intensity focused ultrasound (HIFU) used for the treatment of localized prostate cancers has been demonstrated over the past decade. We present our early results after HIFU used as a single session in patients with clinically localized prostate cancer. A total of 58 patients were treated using the Ablatherm HIFU device with or without transurethral resection of the prostate (TURP). HIFU failure was defined as the presence of a cancer remnant on repeated biopsies or three consecutive increases in the prostate-specific antigen (PSA) >/=1.0 ng/ml. The mean follow-up was 14 months (range, 6-21 months). After HIFU treatment, 78% of patients had a decreased PSA level to <0.5 ng/ml within 3 months. The median value of the last PSA was 0.6 ng/ml and the median nadir PSA was 0.2 ng/ml. The success rates of HIFU were 85, 77 and 47% in low-, intermediate- and high-risk groups, respectively. The HIFU failure rate was closely associated with clinical stage, presence of cancer on TURP chips and nadir PSA on univariate analysis. However, the only significant predictor for HIFU failure was the nadir PSA value by multivariate Cox regression analysis. The operation-related complications were minimal. Although both the period and number of patients were limited to evaluate the clinical efficacy, HIFU appears to be a safe and effective treatment option in selected patients with prostate cancer.     

Prostate cancer with large glands treated with 3-dimensional computerized tomography guided pararectal brachytherapy: up to 8 years of followup

PURPOSE: We report post-brachytherapy results in patients with cancer in a large prostate. MATERIALS AND METHODS: From June 1, 1994 to June 30, 2000, 331 consecutive patients with a large prostate of 50 to 180 cm.3 (median 69) were treated with 3-dimensional computerized tomography guided brachytherapy. Patient age was 42 to 90 years (median 69). Of these patients 327 were available for followup for 2 to 8 years (median 4.5). Patients were stratified according to risk profile. The high risk group had 1 or more high risk factors (prostate specific antigen [PSA] greater than 20 ng./ml., Gleason greater than 7, stage T2b, T3a or T3b) or 2 intermediate risk factors (PSA 10 to 20 ng./ml. and Gleason 7). The high risk group was further stratified into subgroups with a similar risk profile. The intermediate risk group had only 1 high risk factor (PSA 10 to 20 ng./ml. or Gleason 7). The low risk group had PSA less than 10 ng./ml., Gleason less than 7 and stage T1a, b, c or T2a. A dose of 144 Gy. with 125I or 120 Gy. with 103Pd was achieved in 90% to 100% of the target. A total of 31 patients (9%) had previously undergone transurethral resection and 198 (60%) were treated with 3 months of neoadjuvant androgen ablation. RESULTS: Biochemical disease-free survival was achieved in 90% of the 182 patients at high risk, 96% of the 52 at intermediate risk and 99% of the 93 at low risk. Seven patients (2%) required catheterization during year 1 for urinary retention, 11 (3%) required transurethral prostate resection 1 to 4 years after implantation, 3 patients (1%) had grade 1 or 2 incontinence after repeat transurethral prostate resection and 4 (1%) had grade 3 or 4 rectal complications. CONCLUSIONS: The 3-dimensional computerized tomography guided pararectal permanent implant results in a high level of biochemical control with low morbidity at 2 to 8 years in patients with prostate cancer who have a large prostate. There was less favorable biochemical control in patients with PSA greater than 20 ng./ml., Gleason 7 or greater and seminal vesicle invasion.     

The efficacy of cryosurgical ablation of prostate cancer: the University of California, San Francisco experience.

PURPOSE: We analyze biopsy and prostate specific antigen (PSA) results following cryosurgery for patients with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 176 patients underwent 207 cryosurgical procedures for clinically localized (stages T1 to T4) prostate cancer using a multiprobe cryosurgical device. Cancer stage was T1 in 8.7%, T2 in 30%, T3 in 59% and T4 in 2.3% of the 176 patients. Neoadjuvant androgen deprivation was delivered to 101 patients (57%). End points used to determine efficacy of the procedure included analysis of posttreatment serum PSA characteristics (nadir and nonrising status) and biopsy results (absence of cancer). Cryosurgery was considered successful if PSA reached a nadir of less than 0.5 ng./ml. and did not increase by more than 0.2 ng./ml. on 2 consecutive occasions. Mean followup for the entire group was 30.8 months, with 122 patients (60%) followed for 24 or more months and 75 (36%) followed for 36 or more months. RESULTS: Serial PSA data was available after 181 initial and repeat procedures. Nadir PSA was undetectable in 88 patients (49%), between 0.1 and 0.4 ng./ml. in 39 (21%) and 0.5 ng./ml. or greater in 54 (30%) following cryosurgery. After 78 of these procedures (43%) serum PSA reached a nadir of less than 0.5 ng./ml. and failed to increase greater than 0.2 ng./ml. on at least 2 occasions. Prostate biopsy was performed following 167 procedures and was positive after 64 (38%). CONCLUSIONS: Cryosurgery was associated with favorable serum PSA characteristics in 49% of patients 3 years after treatment. Undetectable PSA nadir and pretreatment PSA 10 ng./ml. or less were associated with a favorable outcome, with a biochemical disease-free survival of 77% and 61% 3 years after treatment, respectively.     

Does a delay in initiating definitive therapy affect biochemical recurrence rates in men with clinically localized prostate cancer?

PURPOSE: To assess whether a delay in initiating definitive therapy for clinically localized prostate cancer affects outcome. METHODS: We retrospectively reviewed 393 men with localized prostate cancer treated with radiation therapy or surgery without systemic therapy between 1991 and 2004. Data included: time from diagnosis to treatment initiation (more or less than 3 months); biopsy Gleason score grouped by low (2-6), intermediate (7), or high risk (8-10); clinical stage grouped by low (T1/T2a) or high risk (T2b or higher); pretreatment prostate-specific antigen (PSA) grouped by low (<10 ng/ml), intermediate (10-20), or high risk (>20); and biochemical recurrence-free survival. RESULTS: Median patient age was 63.1 years (range 39.7-79.5). Median pretreatment PSA was 6.5 ng/ml (range 0.4-411). Median time from diagnosis to treatment was 57 days (range 8-2927). A total of 310 patients (79%) were treated within 3 months. Median follow-up was 2.3 years (range 0.1-14.0). On univariate analysis using Kaplan-Meier survival curves and the log-rank test, only pretreatment PSA was associated with worse biochemical recurrence-free survival (P = 0.008). Biochemical recurrence-free survival was not associated with time from diagnosis to treatment (P = 0.28), clinical stage (P = 0.50), or biopsy Gleason score (P = 0.19). The results were the same when analyzed in a multivariable analysis using the Cox proportional hazards model. CONCLUSION: A delay in treatment of > or =3 months does not appear to affect adversely biochemical recurrence-free survival in patients who undergo definitive therapy for clinically localized prostate cancer in those with low risk features.     

Predicting recurrence after radical prostatectomy for patients with high risk prostate cancer

PURPOSE: Previous studies have shown that patients with clinical stage T2c-T3 prostate cancer, serum prostate specific antigen (PSA) at diagnosis greater than 20 ng./ml. or a biopsy Gleason score of 8 to 10 are at high risk for disease recurrence after radical prostatectomy. We determined the most important pretreatment predictors of disease recurrence in this high risk population. MATERIALS AND METHODS: We identified 547 patients with high risk prostate cancer who underwent radical prostatectomy at University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor data base, a longitudinal disease registry of patients with prostate cancer. High risk disease was defined as 1992 American Joint Committee on Cancer clinical stage T2c-T3 disease in 411 patients, serum PSA at diagnosis greater than 20 ng./ml. in 124 and/or biopsy Gleason score 8 to 10 in 114. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment more than 6 months after surgery. The Cox proportional hazards analysis was performed to determine significant independent predictors of disease recurrence. The likelihood of disease recurrence for clinically relevant patient groups was determined using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median followup after surgery was 3.1 years. Disease recurred in 177 patients (32%). Multivariate analysis demonstrated that serum PSA at diagnosis, biopsy Gleason score, ethnicity and the percent of positive prostate biopsies were significant independent predictors of disease recurrence, while patient age and clinical tumor stage were not. Patients with a Gleason score 8 to 10 tumor and a serum PSA of 10 ng./ml. or less had a significantly higher likelihood of remaining disease-free 5 years after surgery than those with PSA greater than 10 ng./ml. (47% versus 19%, p <0.05). Patients with a serum PSA at diagnosis of greater than 20 ng./ml. and a Gleason score of less than 8 had a significantly higher likelihood of remaining disease-free 5 years after surgery than similar patients with a Gleason score of 8 or greater (45% versus 0%, p <0.05). CONCLUSIONS: PSA, Gleason score, ethnicity and the percent of positive prostate biopsies appear to be the most important pretreatment predictors of disease recurrence in men with high risk prostate cancer. Patients with high grade disease may continue to be appropriate candidates for local therapy if PSA is less than 10 ng./ml. at diagnosis or there are fewer than 66% positive prostate biopsies.     

Multicentric Oncologic Outcomes of High-Intensity Focused Ultrasound for Localized Prostate Cancer in 803 Patients

Background

High-intensity focused ultrasound (HIFU) is an emerging treatment for select patients with localized prostate cancer (PCa).

Objectives

To report the oncologic outcome of HIFU as a primary care option for localized prostate cancer from a multicenter database.

Design, setting, and participants

Patients with localized PCa treated with curative intent and presenting at least a 2-yr follow-up from February 1993 were considered in this study. Previously irradiated patients were excluded from this analysis. In case of any residual or recurrent PCa, patients were systematically offered a second session. Kaplan-Meier analysis was performed to determine disease-free survival rates (DFSR).

Measurements

Prostate-specific antigen (PSA), clinical stage, and pathologic results were measured pre- and post-HIFU.

Results and limitations

A total of 803 patients from six urologic departments met the inclusion criteria. Stratification according to d’Amico's risk group was low, intermediate, and high in 40.2%, 46.3%, and 13.5% of patients, respectively. Mean follow-up was 42 ± 33 mo. Mean PSA nadir was 1.0 ± 2.8 ng/ml with 54.3% reaching a nadir of ≤0.3 ng/ml. Control biopsies were negative in 85% of cases. The overall and cancer-specific survival rates at 8 yr were 89% and 99%, respectively. The metastasis-free survival rate at 8 yr was 97%. Initial PSA value and Gleason score value significantly influence the DFSR. The 5- and 7-yr biochemical-free survival rates (Phoenix criteria) were 83–75%, 72–63%, and 68–62% (p = 0.03) and the additional treatment-free survival rates were 84–79%, 68–61%, and 52–54% (p < 0.001) for low-, intermediate-, and high-risk patients, respectively. PSA nadir was a major predictive factor for HIFU success: negative biopsies, stable PSA, and no additional therapy.

Conclusions

Local control and DFSR achieved with HIFU were similar to those expected with conformal external-beam radiation therapy (EBRT). The excellent cancer-specific survival rate is also explained by the possibility to repeat HIFU and use salvage EBRT.     

Radiotherapy for men with isolated increase in serum prostate specific antigen after radical prostatectomy

PURPOSE: In this retrospective study we determined the results of salvage external beam radiation therapy (RT) to the prostate bed for isolated increase of serum prostate specific antigen (PSA) after radical prostatectomy. MATERIALS AND METHODS: A total of 60 patients underwent RT for PSA failure after radical prostatectomy from 1993 to 1999. Median followup was 51 months. Biochemical disease-free survival (bDFS) with a serum PSA of 0.3 ng/ml or less was estimated using the Kaplan-Meier method. Potential prognostic factors were evaluated for significant associations with bDFS. RESULTS: Median PSA before RT was 0.69 ng/ml. Median radiation dose was 64.8 Gy. The 5-year actuarial bDFS was 45%. There were 32 patients with a minimum followup of 4 years (median 73 months) who experienced a 5-year bDFS rate of 43%. PSA before RT (p = 0.016), RT dose (p = 0.026), surgical margin involvement (p = 0.017) and Gleason score (p = 0.018) were identified as prognostic factors for bDFS. A significant association with bDFS was present at 5 years of 65%, 34% and 0% for PSA before RT less than 0.6, 0.6 to 1.2, and greater than 1.2 ng/ml, respectively (p = 0.036). Patients with PSA before RT less than 0.6 ng/ml and total RT dose greater than 64.8 Gy had improved bDFS at 5 years compared to all others (77% vs 32%, p = 0.04). Of 60 patients 3 (5%) experienced chronic grade 3 toxicity. CONCLUSIONS: Optimal benefit from salvage RT was achieved in patients with a PSA less than 0.6 ng/ml and doses of RT greater than 64.8 Gy. Early treatment with a sufficiently high dose of RT maximizes the potential for salvage.