To what extent does the prostate‐specific antigen nadir predict subsequent treatment failure after transrectal high‐intensity focused ultrasound therapy for presumed localized adenocarcinoma of the prostate?

OBJECTIVE: To explore the association between the prostate-specific antigen (PSA) nadir after transrectal high-intensity focused ultrasound (HIFU) therapy for organ-confined prostate cancer and subsequent treatment failure, as defined by the presence of residual disease at biopsy 6 months after treatment. PATIENTS AND METHODS: Between January 1999 and January 2005, 115 patients in a Japanese hospital were treated using a transrectal HIFU system (Sonablate, Focus Surgery, IN, USA) for presumed localized adenocarcinoma of the prostate. All treatments were primary and none of the patients had received hormone therapy. The PSA level was measured at 2-monthly intervals and all patients had a transrectal prostate biopsy taken at 6 months. Multiple logistic regression was used to examine the relationship between PSA nadir and treatment failure, as defined by the presence of disease at biopsy. RESULTS: The PSA nadir was strongly associated with treatment failure (P < 0.001). Patients with a PSA nadir of 0.0-0.2 ng/mL had a treatment failure rate of only 11% (four of 36), compared to 46% (17 of 37) in patients with a PSA nadir of 0.21-1.00 ng/mL and 48% (20 of 42) with a PSA nadir of >1.0 ng/mL. In addition, the PSA nadir was strongly associated with both preoperative PSA level and residual prostate volume. CONCLUSION: There is a clear and intuitive association between the PSA nadir and the risk of treatment failure after HIFU. These data can be used to predict the risk of residual disease in patients with prostate cancer undergoing HIFU therapy. They can also be used to inform where the target PSA nadir should be set for this novel therapy.     

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   

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.     

Transrectal high‐intensity focused ultrasound for treatment of localized prostate cancer

Objectives: To assess the long‐term outcomes of transrectal high‐intensity focused ultrasound (HIFU) for patients with localized prostate cancer. Methods: From May 2003 to present, 137 consecutive patients with T1‐2 prostate cancer were treated using the Sonablate 500 and then followed for more than 12 months after their last HIFU treatment. A prostate biopsy was routinely carried out at 6 months and serum prostate‐specific antigen (PSA) was measured every 3 months after HIFU. Oncological outcomes as well as treatment‐related complications were assessed. Disease‐free survival (DFS) was judged using the Phoenix definition (PSA nadir + 2 ng/mL), negative histological findings and no local or distant metastasis. Results: The median follow up after HIFU was 36 months (range 12–84 months). No patients received adjuvant therapy during this period. The PSA nadir occurred at 2 months after HIFU and the median level was 0.07 ng/mL (0.01–2.01 ng/mL). Of the 133 patients who underwent prostate biopsy or transurethral resection of the prostate at 6 months or later after HIFU, six were positive for cancer cells (4.5%). There were no major postoperative complications, but urge incontinence (16 cases) and dysuria (33 cases) occurred after removal of the urethral catheter. The 5‐year DFS rate was 78% based on these criteria, and 91%, 81% and 62% in the low‐, intermediate‐ and high‐risk group, respectively. Conclusions: HIFU represents an effective, repeatable and minimally invasive treatment. It is particularly effective for low‐ and intermediate‐risk patients, and it should be considered as an option for localized prostate cancer.     

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.     

Cryoablation for clinically localized prostate cancer using an argon-based system: complication rates and biochemical recurrence

OBJECTIVE: To determine the complication rates and biochemical recurrence after cryoablation of the prostate, using an argon gas-based system, in patients with localized prostate cancer. PATIENTS AND METHODS: Between October 1997 and June 1999, 35 patients underwent cryoablation of the prostate (19 after radiation therapy failure and 16 as a primary treatment for localized prostate cancer). All patients had biopsy-confirmed prostate cancer with no seminal vesicle invasion, negative bone scans and a negative lymph node dissection. Patients received 3 months of combined hormonal therapy before cryosurgery. One surgeon performed all the procedures. Biochemical recurrence was defined by an increase in prostate specific antigen (PSA) of >/= 0.2 ng/mL above the PSA nadir. RESULTS: The complications were rectal pain (26%), urinary infection (3%), scrotal oedema (12%), haematuria (6%) and incontinence (6%). Complication rates were higher in those patients who failed after radiation therapy than in those who did not receive radiation (incontinence 11% vs 0%, rectal pain 37% vs 12%) but the difference was not statistically significant. Twenty-two patients (63%) had an undetectable serum PSA nadir (< 0.1 ng/mL) after cryotherapy and 30 (84%) patients had a PSA value of < 1.0 ng/mL. After a mean follow-up of 8.3 months (range 0.2-18), nine patients had biochemical recurrence. The biochemical recurrence-free survival (BRFS) was 70% at 9 months. Patients who had an undetectable PSA nadir had a statistically higher BRSF at 9 months than did patients who had a detectable PSA nadir (89% vs 55%, respectively, P = 0.03). Similarly, patients with a preoperative serum PSA level of < 10 ng/mL had a statistically higher BRFS than patients who had a PSA level of > 10 ng/mL (86% vs 42% at 9 months, P < 0.001). CONCLUSION: A PSA level before cryotherapy of < 10 ng/mL and an undetectable PSA nadir after cryotherapy were associated with the highest BRFS. Cryoablation of the prostate, with low morbidity, seems to be a viable option in managing patients by salvage therapy after radiation therapy and for the primary treatment of clinically localized prostate cancer.     

Six years' experience with high-intensity focused ultrasonography for prostate cancer: oncological outcomes using the new 'Stuttgart' definition for biochemical failure

Study Type – Therapy (outcomes research) Level of Evidence 2b

OBJECTIVE

? To determine oncological outcomes after high‐intensity focused ultrasonography (HIFU) treatment in patients with localized prostate cancer using a new, more accurate, definition (‘Stuttgart’ definition) of biochemical failure.

PATIENTS AND METHODS

? We performed a retrospective review of all patients in our centre who received first‐line treatment with a second‐generation Ablatherm^TM device (EDAP‐TMS, Lyon, France). ? Oncological failure was given either by biochemical failure (prostate‐specific antigen, PSA, nadir plus 1.2 g/mL) (Stuttgart definition) or the start of salvage therapy because of a persistently positive biopsy after the HIFU procedure. ? The 5‐year biochemical‐free survival rate and 5‐year disease‐free survival rate were calculated.

RESULTS

? In total, 53 patients were included (mean age, 72.5 ± 4.5 years, range 60–79 years; 28 low risk and 25 intermediate risk). None had undergone previous hormonal therapy. Mean ±sd follow‐up was 45.4 ± 15.5 months (range 16–71 years). Mean (range) pre‐treatment PSA was 8.5 ± 4 (0.29–18) ng/mL. The median (range) PSA nadir value was 1 (0.01–14) ng/mL and occurred after a mean (range) of 5.09 (3–24) months. ? Overall, 36 patients (67.9%) experienced oncological failure. ? These included 33 cases (62.2%) of biochemical failure. A PSA nadir of ≤0.2, 0.21–1.0 and >1 ng/mL was reached in 20.8%, 30.2% and 49% of patients, respectively, and was associated with biochemical failure in 9.1%, 30.3% and 60.6%, respectively. ? The 5‐year biochemical‐free survival rate and disease‐free survival rate were 21.7% and 13.5%, respectively. In multivariate analysis, a PSA nadir of >1 ng/mL was significantly associated with a risk of biochemical and oncological failure (P= 0.002 and P < 0.001). ? Oncological failure was not associated with any risk group. ? No patient died from prostate cancer.

CONCLUSIONS

? In our experience, Ablatherm^TM treatment for clinically localized prostate cancer was associated with a high rate of biochemical failure as determined by the ‘Stuttgart’ definition, and did not achieve effective cancer control. ? The PSA nadir value after HIFU treatment was a significant predictor of treatment failure.     

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   

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.     

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.     

Conformal proton therapy for early-stage prostate cancer

OBJECTIVES: To assess the effect of proton radiation on clinical and biochemical outcomes for early prostate cancer. METHODS: Three hundred nineteen patients with T1-T2b prostate cancer and initial prostate-specific antigen (PSA) levels 15.0 ng/mL or less received conformal radiation doses of 74 to 75 cobalt gray equivalent with protons alone or combined with photons. No patient had pre- or post-treatment hormonal therapy until disease progression was documented. Patients were evaluated for biochemical disease-free survival, PSA nadir, and toxicity; the mean and median follow-up period was 43 months. RESULTS: Overall 5-year clinical and biochemical disease-free survival rates were 97% and 88%, respectively. Initial PSA level, stage, and post-treatment PSA nadir were independent prognostic variables for biochemical disease-free survival: a PSA nadir 0.5 ng/mL or less was associated with a 5-year biochemical disease-free survival rate of 98%, versus 88% and 42% for nadirs 0.51 to 1.0 and greater than 1.0 ng/mL, respectively. No severe treatment-related morbidity was seen. CONCLUSIONS: It appears that patients treated with conformal protons have 5-year biochemical disease-free survival rates comparable to those who undergo radical prostatectomy, and display no significant toxicity. A Phase III randomized dose-escalation trial is underway to define the optimum radiation dose for early-stage prostate cancer.     

Single-session primary high-intensity focused ultrasonography treatment for localized prostate cancer: biochemical outcomes using third generation-based technology

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The experience with HIFU as a minimally invasive treatment for localized prostate cancer is relatively new and most reports are from European centres. Our study is unique in five regards: 1. Data was collected prospectively. 2. All patients were treated with contemporary technology. 3. Outcomes are reported after a single HIFU session using two definitions of biochemical failure that have the ability to predict longer‐term clinical failure after primary ablative therapies for prostate cancer (Stuttgart definition for HIFU and Horwitz definition for radiation). 4. All patients were treated in a single centre. 5. No patients underwent peri‐HIFU TURP. The present study represents the largest North American prospective cohort of primary HIFU for prostate cancer with mid‐term oncological outcome data.

OBJECTIVE

• ? To assess 4‐year biochemical failure (BCF) rates in patients after high‐intensity focused ultrasonography (HIFU) treatment using the Horwitz and Stuttgart definitions.

PATIENTS AND METHODS

• ? A total of 447 consecutive patients were treated with a single session of HIFU between May 2005 and December 2010.
• ? Follow‐up included prostate‐specific antigen (PSA) measurement every 3 months during the first year and every 6 months thereafter.
• ? Patients who had previously received radiation, androgen deprivation or HIFU therapy, and patients with <2 consecutive PSA measurements were excluded.
• ? BCF was reported using the Stuttgart (PSA nadir + 1.2 ng/mL rising) and the Horwitz (two consecutive increases of at least 0.5 ng/mL) definitions.

RESULTS

• ? In all, 402 patients met the inclusion criteria and the median (range) follow‐up was 24 (6–48) months.
• ? Of these patients, 183 (45.5%) had low and 219 (54.5%) had intermediate D'Amico's risk stratification disease.
• ? Mean and median absolute PSA nadir levels were 0.36 ± 0.69 and 0.1 ng/mL (Q₁:0, Q₃:0.37), respectively and these were achieved in median time of 3 months.
• ? Overall 4‐year mean (range) BCF‐free rates were 68 (61–75)% and 72 (68–77)% according to the Stuttgart and Horwitz definitions at 4 years, respectively.
• ? Mean (range) BCF‐free rates were significantly higher for a PSA nadir ≤0.5 ng/mL and prostate volume ≤30 mL for both definitions at 4‐year follow‐up [Stuttgart: 79 (72–86)% vs. 25 (13–38)%; Horwitz: 82 (77–87)% vs. 33 (21–44)%] and [Stuttgart: 72 (64–79)% vs. 56 (42–69)%; Horwitz: 75 (69–80)% vs. 63 (53–74)%], respectively.
• ? Pre‐treatment PSA and PSA nadir of >0.5 ng/mL were the predictors of BCF using both definitions.

CONCLUSIONS

• ? Primary HIFU appears to result in promising 4‐year BCF‐free rates in individuals with low‐ and intermediate‐risk prostate cancer who achieve PSA nadir <0.5 ng/mL.
• ? A prostate volume <30 mL is associated with PSA nadir levels of <0.5 ng/mL suggesting a potential role for pretreatment volume reduction (medically or surgically) in larger prostates.

     

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.     

High‐intensity focused ultrasound for localized prostate cancer: initial experience with a 2‐year follow‐up

OBJECTIVE

To report on the short‐term functional and oncological results, from one institution, of high‐intensity focused ultrasound (HIFU) for treating localized prostate cancer.

PATIENTS AND METHODS

Over a 3‐year period, 43 patients with localized prostate cancer were scheduled for HIFU in the primary (31) and salvage (12) settings using a second‐generation Ablatherm^TM device (EDAP, Lyon, France). Oncological failure was defined by several criteria, including biochemical failure (assessed using both the Phoenix definition of the nadir + 2 ng/mL) and the current Food and Drug Administration (FDA) trial endpoint of a prostate‐specific antigen (PSA) level of ≥0.5 ng/mL, or starting salvage therapy, or the presence of cancer on biopsy after treatment.

RESULTS

Three patients had their procedures abandoned due to technical limitations/rectal wall thickness. The mean PSA levels in the primary and salvage groups were 9.2 and 5.1 ng/mL, respectively. The mean HIFU treatment time in the primary and salvage groups was 71.1 and 63.3 min, respectively. Using the Phoenix definition of biochemical failure, HIFU treatment failed in 13 patients in the primary group (46%) and five in the salvage group. Using the FDA trial endpoint, HIFU failed in 21 patients in the primary group (75%) and eight in the salvage group. One man died from metastatic prostate cancer 18 months after salvage HIFU. There were two urethral strictures in the primary (7%) and one in the salvage treatment group. There were two prostato‐rectal fistulae in the salvage HIFU group.

CONCLUSIONS

HIFU is proposed to be a minimally invasive low‐morbidity ablative treatment for localized prostate cancer, and with good efficacy. The present limited series is unable to support these claims. There were significant rates of complications and oncological failure in both the primary and salvage setting. As a result we have suspended our programme pending further evidence of its safety and efficacy.     

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study

We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, 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 prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.     

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.     

Usefulness of ultrasensitive prostate-specific antigen assay for early detection of biochemical failure after radical prostatectomy

BACKGROUND: In order to assess whether the prostate-specific antigen (PSA) nadir obtained with an ultrasensitive PSA assay can be used as a prognostic indicator for patients undergoing radical prostatectomy, we investigated it retrospectively. METHODS: Between October 1997 and July 2003, 46 patients underwent radical prostatectomy for prostate cancer at our institution. None of them received preoperative treatment. Levels of PSA were measured with an ultrasensitive PSA assay every 1-3 months after prostatectomy. Biochemical recurrence was defined as a PSA level of 0.2 ng/mL or higher. RESULTS: There was a significant difference in PSA nadir between the biochemical recurrence group and the no recurrence group (P < 0.001). The receiver operating characteristics (ROC) curve gave an optimal cut-off value for PSA nadir of 0.01 ng/mL, demonstrating a significant difference in biochemical recurrence after radical prostatectomy. No patient with a PSA nadir level <0.01 ng/mL showed biochemical failure, while 15 out of 22 patients with PSA nadir levels >or=0.01 ng/mL showed biochemical failure. CONCLUSION: The PSA nadir level obtained using an ultrasensitive PSA assay is an excellent predictor of biochemical recurrence after radical prostatectomy. Early detection of recurrence offers the possibility of early salvage therapy.     

Usefulness of the nadir value of serum prostate-specific antigen measured by an ultrasensitive assay as a predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer

INTRODUCTION: The objective of this study was to determine whether the nadir value of serum prostate-specific antigen (PSA) measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: This study included 127 patients who underwent radical prostatectomy for clinically localized prostate cancer without neoadjuvant hormonal therapy and were pathologically diagnosed as negative for lymph node metastasis. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and the findings were analyzed with respect to several clinicopathological factors. In this series, biochemical recurrence was defined as PSA persistently >0.2 ng/ml. RESULTS: Based on the nadir PSA value, we divided 127 patients into three groups as follows: group A (n=99):or=0.05 ng/ml. The nadir PSA value was significantly associated with preoperative PSA value, but not other conventional clinicopathological prognostic parameters. During the observation period (median 31 months, range 6-75 months), biochemical recurrence occurred in 16 patients, that is, 1 in group A (6.3%), 4 in group B (25.0%), and 11 in group C (91.7%). Multivariate analysis using the Cox proportional hazards regression model indicated that the nadir PSA value was an independent predictor for biochemical recurrence after radical prostatectomy. CONCLUSION: These findings suggest that the nadir serum PSA value measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer, and that careful follow-up should be considered in cases demonstrating a nadir PSA value>0.01 ng/ml because of the significantly higher probability of biochemical recurrence in such cases.     

The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection

To decrease side effects observed after high-intensity focused ultrasound (HIFU) treatment for localized prostate cancer and to re-establish normal micturition in a patient population that often presents with concomitant prostate enlargement, the impact of a combined transurethral resection of the prostate (TURP) and HIFU has been evaluated. TURP and HIFU treatments were performed under the same spinal anesthesia. For the HIFU treatments, the Ablatherm device (EDAP SA, Lyon, France) was used. Selection criteria for HIFU treatment were localized prostate cancer, no previous treatment for prostate cancer, and prostate-specific antigen (PSA) ≤ 15 ng/mL at diagnosis. All patients meeting these criteria were considered for treatment and analysis. PSA nadir and stability, histology, International Prostate Specific Score (IPSS) and IPSS-quality of life, and morbidity were assessed during follow-up; 271 patients were selected: 96 in the HIFU group and 175 in the TURP plus HIFU group. A statistically significant impact was observed on catheter time (40.0 days versus 7.0 in median), incontinence (15.4% versus 6.9%), urinary infection (47.9% versus 11.4%), and the evolution of the post-treatment IPSS (8.91 versus 3.37 in average) in favor of the TURP plus HIFU group. No significant changes were observed regarding efficacy during short-term follow-up when considering a 25% retreatment rate in the HIFU group versus a 4% retreatment rate in the TURP plus HIFU group. The combination of a TURP and HIFU treatment reduces the treatment-related morbidity significantly. The patient management after a combined TURP and HIFU treatment is comparable with the management after a single TURP.     

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.