Salvage radiation for a rising PSA following radical prostatectomy

The purpose of this study was to evaluate the efficacy and complications of postprostatectomy therapeutic irradiation (RT) in patients with known residual disease. Between 1991 and 2003, 170 patients received therapeutic irradiation for a rising PSA following radical prostatectomy. No patients had clinical or radiological evidence of metastatic disease. The median pre-RT PSA level was 1.2 ng/mL (range, 0.2-43 ng/mL). During irradiation, the PSA level was checked weekly (median PSA determinations: 5, range, 2-7). A patient was considered to have a rise/fall of PSA if the level changed by > or = 0.2 ng/mL. There were 149 patients who received photon irradiation (median dose, 6800 cGy) and 21 patients received a combination of photon and neutron irradiation to a median photon dose equivalent of 7800 cGy. A patient was considered to have biochemical failure if his PSA level postnadir was measured at >0.2 ng/mL. Complications were graded according to the RTOG toxicity scale. The median follow-up time was 49 months (range, 1-137 months). Sixty-four patients (38%) had evidence of biochemical failure. The 7 year overall survival was 84%. At 7 years, the actuarial biochemical relapse free survival (bRFS) was 44%. Of the 59 patients with a preradiation PSA <1 ng/mL, the 5 year bRFS was 81%. This compares with 45% for both the PSA 1-4 and PSA >4 ng/mL group (P = 0.00008). The 3-year bRFS rates for patients whose PSA levels increased, decreased, and remained the same during radiation were 20%, 65%, and 76%, respectively (P = 0.0005). Overall survival at 7 years in the decreased PSA group was 88% compared to 67% for those whose PSA level increased (P = 0.43). Thirty-three percent and 19% of the patients experienced Grade 2 genitourinary (GU) and gastrointestinal (GI) complications, respectively. Six percent and 3% of the patients had Grade 3 GU and GI complications, respectively. On univariate and multivariate analysis, the factors significantly associated with a favorable outcome were a declining PSA during RT and a pre-RT PSA <1 ng/mL (P < 0.001). Radiation therapy is an effective treatment modality for select patients with a biochemical recurrence following radical prostatectomy. Patients with a low preradiation PSA level (<1.0 ng/mL) had a significantly better outcome, which supports the early use of therapeutic radiation. The observation that patients with a rising PSA level during treatment do poorly supports the routine practice of monitoring these levels during radiotherapy.     

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.     

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.     

Prostate specific antigen nadir determined using ultra-sensitive prostate specific antigen as a predictor of biochemical progression after radical prostatectomy in Japanese males

OBJECTIVES: We examined whether the prostate specific antigen (PSA) nadir is a good predictor of biochemical failure after radical prostatectomy. METHODS: We retrospectively reviewed clinico-pathological data in 257 patients who underwent radical prostatectomy. Twenty-nine patients of whom PSA nadir did not reach 0.1 ng/mL and three patients in whom second line therapy was started before biochemical failure were excluded, and 225 patients were subject to this study. We evaluated the changes in PSA value at very low (from less than 0.01-0.10 ng/mL) levels using an ultra-sensitive PSA assay after radical prostatectomy. Biochemical failure was defined as three consecutive elevations of PSA to above 0.1 ng/mL. RESULTS: Biochemical failure-free survival was attained by 89.9% of patients at 1 year, 83.0% at 2 years, and 81.0% at 5 years. PSA nadir more than 0.01 ng/mL was strongly associated with biochemical failure after radical prostatectomy (P < 0.0001). Mean time to reach PSA nadir was 3.1 months. Preoperative PSA > 20 ng/mL (P = 0.0013), clinical T stage = T2 (P = 0.0462), Gleason score 8-10 (P = 0.0243) were also independent predictors of biochemical progression. CONCLUSIONS: Prostate specific antigen nadir determined by ultra-sensitive PSA assay is an important parameter that is objective, reliable, and easily measured, and useful for predicting the subgroups of patients both most likely and unlikely to exhibit biochemical progression.     

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.     

Salvage radiotherapy for biochemical recurrence after radical prostatectomy

OBJECTIVE: To evaluate the clinical outcome of salvage radiotherapy (RT) for biochemical recurrence after radical prostatectomy (RP) at our institution. PATIENTS AND METHODS: Between March 1999 and January 2004, 37 patients had salvage RT for prostate-specific antigen (PSA) failure after RP, including eight who had had neoadjuvant hormone therapy. After surgery, PSA was measured with ultrasensitive immunoassays. In all patients RT was delivered to the prostatic bed at a total dose of 60 Gy with a four-field box technique. RESULTS: The median (range) PSA level before salvage RT was 0.146 (0.06-3.216) ng/mL and RT was started at a PSA level of <0.5 ng/mL in 34 of the 37 patients (92%). With a median follow-up of 31.9 (0-69.8), months, 11 patients (30%) had disease progression after RT and the 3- and 5-year progression-free probability was 74% and 54%, respectively. Univariate analysis showed that clinical and pathological tumour stages and PSA level before RT (>0.15 vs < or = 0.15 ng/mL) were significant predictors of disease progression. There were no late adverse events related to RT. CONCLUSION: Salvage RT for biochemical failure after RP at a low PSA level, using ultrasensitive immunoassays for monitoring, is a reasonably effective treatment. A relatively low radiation dose (60 Gy) seems to be effective.     

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.     

The effect of radiotherapy on patients with prostate specific antigen failure after radical prostatectomy

We studied the effect of radiotherapy on patients with re-elevation of prostate specific antigen (PSA) after radical prostatectomy. Radiotherapy was performed on 8 patients with re-elevated PSA after radical prostatectomy without any previous treatment. Pathological stages were B in 2 patients, and C in 6 patients. Patients received three-dimensional dynamic conformal radiotherapy, and irradiation doses ranged from 44 to 70 Gy (median 60). The target area of irradiation included prostatic bed and seminal vesicles. PSA levels before radiotherapy were 0.31-1.9 ng/ml (median 0.40). In 7 patients, PSA levels decreased and no increase has been observed thereafter. In one patient, PSA level increased during radiotherapy; therefore, the treatment was discontinued at 44 Gy. Two patients suffered grade 1 to 2 acute toxicities, and no late toxicity has been observed so far. Radiotherapy is considered one of the effective treatments for re-elevation of PSA after radical prostatectomy.     

Salvage high‐intensity focused ultrasound for biopsy‐confirmed local recurrence of prostate cancer after radical prostatectomy

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To present experience in high‐intensity focused ultrasound (HIFU) used as a salvage therapy for biopsy‐confirmed local recurrence at the vesico‐urethral anastomosis after radical prostatectomy (RP).

PATIENTS AND METHODS

From July 2006, four patients diagnosed with prostate cancer recurrence after RP were treated with HIFU, with or without salvage radiotherapy, using the Sonablate® 500 (Focus Surgery, IN, USA). Biochemical failure was defined as in increase in prostate‐specific antigen (PSA) level of >0.2 ng/mL. No patients received any adjuvant therapy after HIFU therapy before reporting failure.

RESULTS

The mean age and initial PSA level before RP was 74 years and 10.0 ng/mL, respectively. After RP, one patient was stage T2aN0M0, two were stage T3N0M0 and the last had an unknown pathological stage. Three patients received external beam radiotherapy as salvage therapy after RP. The mean PSA level before HIFU, tumour volume at the vesico‐urethral lesion and operative duration were 4.3 ng/mL, 4.6 mL and 27 min, respectively. Adenocarcinomas were confirmed by biopsy of the tumour at the vesico‐urethral anastomotic lesion before HIFU. At 24 months of follow‐up, patients 2 and 4 were classified a biochemically disease‐free. Biopsies at the anastomotic site after HIFU in three patients showed no malignancy, with fibrosis. There were no complications.

CONCLUSION

Salvage HIFU for patients with recurrence after RP is feasible, even though they received salvage radiotherapy before HIFU. More patients and a longer follow‐up are needed to evaluate the safety and oncological adequacy of this new approach.     

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.     

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.     

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 and localized prostate cancer: efficacy results from the European multicentric study

PURPOSE: To describe the safety and efficacy of high-intensity focused ultrasound (HIFU) for the treatment of prostate cancer as assessed in a Phase II/III prospective multicentric clinical trial. PATIENTS AND METHODS: Patients (N = 402) presenting with localized (stage T(1-2)N(0-x)M(0)) prostate cancer between 1995 and 1999 at six European sites who were not candidates for radical prostatectomy were treated with HIFU under general or spinal anesthesia. Their mean age was 69.3 +/- 7.1 (SD) years, the mean prostate volume 28.0 +/- 13.8 cc, and the mean serum prostate specific antigen (PSA) concentration 10.9 +/- 8.7 ng/mL. Nearly all (92.2%) of the patients had one to four positive biopsy samples at baseline. The Gleason scores were 2 to 4 for 13.2% of the patients, 5 to 7 for 77.5%, and 8 to 10 for 9.3%. During the follow-up, random sextant biopsies and serum PSA measurements were performed. Any positive sample in biopsies performed after the last treatment session resulted in a "HIFU failure" classification. RESULTS: The patients received a mean of 1.4 HIFU sessions. The mean follow-up duration was 407 days (quartile 1 135 days, median 321 days, quartile 3 598 days). The negative biopsy rate observed in the T1-2 primary-care population was 87.2%. These results were also stratified according to the usual disease-related risk classification, and as much as a 92.1% negative biopsy rate was observed in low-risk patients. Nadir PSA results correlated with prostate size and the clinical procedure. CONCLUSION: These short-term results obtained on a large cohort confirm that HIFU is an option to be considered for the primary treatment of localized prostate cancer.     

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.     

Neoadjuvant Hormonal Therapy Improves the Outcomes of Patients Undergoing Radioactive Seed Implantation for Localized Prostate Cancer

Neoadjuvant hormonal therapy (NHT) has been extensively studied in patients undergoing radical prostatectomy and external-beam irradiation for prostate cancer. While there are a few reports in the literature on its use in men undergoing brachytherapy, little information exists about its beneficial effects in such patients. In this report, we describe the effects of NHT on prostate volume (PV) prior to seed implantation and on the prostate specific antigen (PSA) and postimplant biopsy outcomes of patients who presented with high-risk features. Hormone therapy (leuprolide and flutamide 750 mg/day) was given to 145 patients for 3 months prior to and for 3 months after permanent iodine-125 (160 Gy) or palladium-103 (115 Gy) seed implantation. Of these, 28 (19%) received NHT because of a preimplant PV >50 cc, and 117 patients received NHT because they had a PSA >10 ng/mL, Gleason score >/=7, or clinical stage >/=T(2b). All patients underwent implantation using the real-time intraoperative method, and no patients received external-beam irradiation. Of the 145 patients treated, 67 (46%) had a PSA >10 ng/mL (range 1.9-57 ng/mL; mean 12.2 ng/mL), 50 (35%) had Gleason score >/=7, and 80 (55%) had stage >/=T(2b) disease. Prostate volume was measured in 106 patients prior to NHT and 3 months later immediately prior to the seed implant. The mean PV was 50.4 cc (range 17-150 cc), whereas the mean PV after NHT was 31 cc (range 11.7-73.7 cc). The mean PV reduction was 35% (range 2%-62%). Volume reduction was compared in those patients who presented with a PV <40 cc (N = 51) and those with a PV >/=40 cc (N = 56). The mean reduction for the smaller glands was 29% (range 2%-54%) compared with 41% (range 7%-62%) for the larger glands (P < 0.05). Patients were followed for a minimum of 1 year (range 1.0-6.4; mean 2.2 years). The 4-year actuarial rate of freedom from PSA failure (PSA >1.0 ng/mL with two consecutive elevations) was 85%. There was no difference in rates of freedom from PSA failure for those with initial Gleason 2-4 (96%), 5-6 (78%), 7 (80%), or 8-9 (83%; P = 0.5). Control rates were 85% for patients with PSA 20 ng/mL (P = 0.8). There was a trend to decreased control rates with higher-stage disease (98% for T(1)-T(2a) v 68% for T(2c)), but these differences were likewise not significant (P = 0.12). The control rates for the 28 low-risk patients with enlarged prostate glands were compared with those of the 117 with high-risk features and were not different (100% v 82%; P = 0.1). There were 62 patients who agreed to eight-core prostate biopsies 2 years after implantation, and 60 (97%) were negative for tumor. This trial shows that NHT can reduce PV an average of 35% prior to seed implantation with the greatest reduction found in patients with larger prostates (41%). Hormonal therapy also appears to improve biochemical (PSA) control and local control (prostate biopsy) in patients with high-risk disease, yielding results similar to those in men with low-risk prostate cancer.     

Ultrasensitive Assay of Prostate-Specific Antigen for Early Detection of Residual Cancer after Radical Prostatectomy

Objectives : Perhaps the greatest value of PSA determination in the treatment of prostate cancer is in determining persistent disease after a radical prostatectomy. We investigated the ability of an ultrasensitive PSA assay to detect residual prostate cancer in men at risk for recurrence after a radical prostatectomy.
Methods : Using the Immulite third-generation PSA assay (detection limit, less than 0.003 ng/mL), and the standard IMx PSA assay, we determined PSA levels in 205 serum samples serially obtained from 34 men after a radical prostatectomy. The average days from surgery to serum sampling was 430 (range, 63 to 1 296). Patients were classified as having nonaggressive or aggressive cancers, based on clinicopathologic findings. A biochemical relapse was arbitrarily defined.
Results : All 1 7 patients with nonaggressive cancers had PSA values of less than 0.02 ng/mL throughout the sampling period. Two of these patients (12%) had 2 or more consecutive PSA increases and were considered as a biochemical relapse. In contrast, 14 (82%) of 1 7 patients with aggressive cancers fit criteria of a biochemical relapse. All of the relapses were identified within 2 years after surgery. The IMx assay detected only 7 biochemical relapses during the same sampling period.
Conclusions : Using the Immulite PSA assay, relapse detection times may be shortened allowing for most serological recurrences to be detected within 2 years after a radical prostatectomy. Patients with aggressive cancers may require frequent postoperative PSA determinations with a highly sensitive PSA assay which would allow early intervention when treatments for relapse are effective.     

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.     

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.     

Radiotherapy after radical prostatectomy: treatment outcomes and failure patterns

Objectives. To define the optimal role for radiotherapy (RT) after radical prostatectomy (RP) and to characterize specific patterns of PSA failure in this setting.Methods. The records of 105 patients who underwent RT after RP (69 received therapeutic RT because of an elevated prostate-specific antigen [PSA] level, 36 received immediate adjuvant RT) were reviewed. The median follow-up was 35 months after RT and 57 months after RP. Radiation success was defined as achievement and maintenance of a PSA less than 0.2 ng/mL. Preoperative, pathologic, and postoperative characteristics were examined for their ability to predict success after RT. Patterns of PSA recurrence after RT were also examined by determining the PSA nadir, PSA velocity, and timing of androgen-deprivation therapy.Results. Of 105 patients, 47 experienced biochemical failure. Actuarial 3 and 5-year progression-free survival estimates for all patients were 55% and 43%, respectively. Significant favorable predictors of response to RT by multivariate analysis were preoperative PSA less than 20 ng/mL and the use of adjuvant RT. However, patients who received therapeutic RT with a pre-RT PSA less than 1.0 ng/mL demonstrated progression-free outcome equivalent to those who received adjuvant RT. Two distinct patterns of PSA failure were observed on the basis of PSA nadir after RT. Patients whose PSA failed to reach a nadir less than 0.2 ng/mL after RT had progression with a high PSA velocity (1.5 ng/mL/yr). Patients whose PSA reached a nadir less than 0.2 ng/mL but who subsequently had treatment failure progressed later with a lower PSA velocity (0.36 ng/mL/yr).Conclusions. RT is effective in select patients after RP. Given the low PSA velocity consistent with persistent local disease in nearly 50% of patients in whom RT failed, more effective local therapy is needed after RP in high-risk patients.