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.     

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.     

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.     

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.

     

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 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.     

High-dose rate iridium-192 brachytherapy and external beam radiation therapy for prostate cancer with or without androgen ablation

Aim: To report the results of our feasibility study incorporating iridium‐192 high‐dose‐rate (HDR) afterloading brachytherapy and external beam radiation therapy (EBRT) for the treatment of prostate carcinoma and to assess the role of androgen ablation in conjunction with this treatment option. Methods: From July 2000 to June 2002, 42 patients with clinically localized or locally extensive prostate carcinoma were treated with HDR iridium‐192 brachytherapy and EBRT with or without androgen ablation. The median follow up was 16.5 months. Results: The technique of HDR brachytherapy and EBRT proved to be feasible with acceptable morbidities. Continuous prostate‐specific antigen (PSA) reduction was noted in all patients and no PSA failure was noted during follow up. Within 1 year, the decline of PSA nadir values less than 1 ng/mL was faster in patients with the addition of androgen blockade (P = 0.001). However, within 1 year, PSA nadir values less than 1.0 ng/mL can be achieved in all patients whose initial PSA is less than 20 ng/mL, with or without hormone blockade. Conclusions: The need for hormonal therapy in favorable‐risk brachytherapy patients (PSA < 20 ng/mL) might be less than the need for intermediate‐ or high‐risk patients. The use of hormonal therapy in intermediate‐risk patients (PSA ≥ 20 ng/mL) treated with HDR brachytherapy and pelvic EBRT is appealing, considering the favorable results. High dose rate brachytherapy appears to be an effective treatment for clinically localized and locally extensive prostate cancer, with minimal morbidity.     

Single application of high‐intensity focused ultrasound as a first‐line therapy for clinically localized prostate cancer: 5‐year outcomes

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High‐intensity focused ultrasound (HIFU) therapy has been proposed for the treatment of localized prostate cancer (PCa) for all risk levels of tumour recurrence. The study adds data on the efficacy of a single HIFU application in the treatment of PCa with different risks of recurrence. Durable cancer control was achieved in 81.7% of patients with low‐risk disease, with rates of efficacy declining in intermediate‐ and high‐risk tumours. The data suggest that the principal domain for minimal invasive HIFU should be low‐risk disease.

OBJECTIVE

• ? To report cancer control results after a single application of high‐intensity focused ultrasonography (HIFU) in patients with localized prostate cancer (PCa), stratified by tumour recurrence risk according to D'Amico risk classification.

PATIENTS AND METHODS

• ? In a retrospective single‐centre study, we analysed the outcomes of patients with localized PCa who were treated with curative intent between December 2002 and October 2006 using an Ablatherm HIFU device (EDAP‐TMS, France).
• ? Transurethral resection of the prostate or adenomectomy were performed before HIFU to downsize large prostate glands.
• ? Oncological failure was determined by the occurrence of biochemical relapse, positive biopsy and/or metastasis. Biochemical relapse was defined as a PSA nadir +1.2 ng/mL (Stuttgart definition), or as a rise in PSA level to ≥0.5 ng/mL if PSA doubling time was ≤6 months. Kaplan–Meier analysis was performed for survival estimates.

RESULTS

• ? A total of 191 consecutive patients were included in the study. The median (range) patient age was 69.7 (51–82) years, and 38, 34 and 28% of these patients were in the low‐, intermediate‐ and high‐risk groups, respectively.
• ? The median (range) follow‐up was 52.8 (0.2–79.8) months.
• ? At 5 years, overall and cancer‐specific survival rates were 86.3% and 98.4%, respectively.
• ? Stratified by risk group, negative biopsy rates were 84.2%, 63.6%, and 67.5% (P = 0.032), 5‐year biochemical‐free survival rates were 84.8%, 64.9% and 54.9% (P < 0.01), and 5‐year disease‐free survival rates were 81.7%, 53.2% and 51.2% (P < 0.01), respectively.

CONCLUSION

• ? Single‐session HIFU is recommended as a curative approach in elderly patients with low‐risk PCa. Patients at higher risk of tumour progression should be counselled regarding the likely need for salvage therapy, including repeat HIFU.

     

High-intensity focused ultrasound as salvage therapy for patients with recurrent prostate cancer after external beam radiation, brachytherapy or proton therapy

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Salvage HIFU is a promising treatment option for local recurrence after radiation therapy, with morbidity comparable with other forms of salvage treatment. This study showed a long‐term follow up of salvage HIFU in men with recurrence of localized prostate cancer following not only external beam radiation therapy but also brachytherapy or proton therapy.

OBJECTIVE

To investigate the use of high‐intensity focused ultrasound (HIFU) as a salvage therapy in patients with recurrence of localized prostate cancer after external beam radiation (EBRT), brachytherapy, or proton therapy.

PATIENTS AND METHODS

We retrospectively reviewed the charts of all patients who had undergone salvage HIFU for biopsy‐proven prostate cancer after primary radiation therapy. Patient characteristics and oncological outcomes were assessed.

RESULTS

Records of 22 patients with a median (range) follow‐up of 24 (5–80) months were reviewed. Patients were men with presumed organ‐confined disease who had been treated with salvage HIFU following recurrent disease after EBRT (fourteen patients), brachytherapy (five patients: four with high‐dose brachytherapy using In¹⁹²; and one with low‐dose brachytherapy using Au⁹⁸) or proton therapy (three patients). The median (range) age at salvage HIFU was 65 (52–80) years, with a median (range) prostate‐specific antigen (PSA) level before radiation therapy of 14.3 (5.7–118) ng/mL and a median (range) PSA level of 4.0 (1.2–30.1) ng/mL before HIFU. The median (range) period to HIFU after radiation therapy was 36 (4–96) months. The biochemical disease‐free survival (bDFS) rate in all patients at 5 years was 52%. Rates of bDFS in low‐, intermediate‐ and high‐risk groups were 100%, 86%, and 14%, respectively. One of the twelve patients who received post‐HIFU prostate biopsy showed malignancy. Side effects included urethral stricture in four patients, grade I urinary incontinence in four patients, rectourethral fistula and epididymitis in one of each patient.

CONCLUSION

Salvage HIFU is a promising treatment option for local recurrence after radiation therapy, with morbidity comparable with other forms of salvage treatment.     

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.     

Endorectal magnetic resonance imaging and magnetic resonance spectroscopy to monitor the prostate for residual disease or local cancer recurrence after transrectal high-intensity focused ultrasound

OBJECTIVE

To assess the role of magnetic resonance imaging (MRI) for evaluating changes in the prostate after transrectal high‐intensity focused ultrasound (HIFU) for treating prostate cancer, correlating the findings with histology to assess its possible role in predicting the outcome, evaluating residual cancer or local recurrence of disease.

PATIENTS AND METHODS

Ten patients with prostate cancer were assessed with MR and MR spectroscopy (MRS) before and at 1, 4 and 12 months after HIFU, assessing the glandular volume and MRI and MRS data after HIFU. These data were correlated with the prostate‐specific antigen (PSA) levels at each examination (suspicious for residual cancer if >0.5 ng/mL) and with histological findings of prostate biopsy sampling at 6–8 months (random or targeted at suspicious MR areas).

RESULTS

Variations in volume during the follow‐up were not associated with treatment outcome. MRI was suspicious for residual cancer in one patient at 1 month and in another two at 4 months; in all three patients (one with a PSA level of <0.5 ng/mL) targeted biopsies were positive for cancer. MRI was negative in seven patients; in six of these (one with a PSA level of >0.5 ng/mL) random biopsies were negative, and in one the random biopsies were positive for residual cancer. At 4 months there was a statistically significant difference (P = 0.015) between patients responsive to treatment and those with persistent disease, by combining negative MRI with a PSA level of <0.5 ng/mL; MRS data were suitable for analysis only in three patients with partial necrosis.

CONCLUSION

Our preliminary data support the role of MRI in association with PSA levels as a useful and accurate tool in the follow‐up of patients treated with HIFU for prostate cancer. However, considering the economic issue, it should not be used routinely and should be limited to detecting residual cancer (in patients with a PSA level of >0.5 ng/mL) with the main purpose of improving the detection rate of transrectal ultrasonography (TRUS)‐guided prostate biopsy. MRS data had no additional value over MRI. Further evaluation is needed to compare the use of contrast media and other techniques (e.g. colour Doppler TRUS) in detecting residual or local recurrent cancer.     

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.     

Failing to achieve a nadir prostate-specific antigen after combined androgen blockade: Predictive factors

Objectives:   To determine the optimal cut-off of a nadir prostate-specific antigen (PSA) for prediction of progression within 24 months after combined androgen blockade (CAB) and to analyze predictive factors of failing to achieve the nadir PSA.
Methods:   We retrospectively reviewed the medical records of 343 patients with prostate cancer treated with CAB from 2000 to 2005. We determined the nadir PSA level that predicts progression to hormone refractory prostate cancer (HRPC) at 24 months after CAB. Predictive factors for failing to achieve a determined nadir PSA were analyzed.
Results:   Mean age was 74.0 years. Mean follow up was 42.1 month. Seventy-seven patients experienced progression to HRPC. A nadir PSA of 1.0 ng/mL predicts progression to HRPC at 24 months. Predictive factors for failing to achieve a nadir PSA of 1.0 ng/mL or less include pretreatment PSA, percentage positive biopsy core, Gleason score, serum hemoglobin, stage, and extent of bone metastasis in univariate analysis. Pretreatment PSA (>50 ng/mL) and serum hemoglobin (<12 g/dL) were significant factors to predict failing to achieve a nadir PSA of 1.0 ng/mL or less in logistic regression analysis.
Conclusions:   A nadir PSA of 1.0 ng/mL can predict progression to HRPC after CAB. Pretreatment PSA and serum hemoglobin are significant predictors of failing to achieve a nadir PSA of 1.0 ng/mL or less.     

Predictors of androgen independence in metastatic prostate cancer

OBJECTIVE: To assess the factors that influence the onset of androgen independence (AI, which heralds a dismal outcome) in patients with metastatic prostate carcinoma. PATIENTS AND METHODS: The records of 361 consecutive patients with prostate carcinoma diagnosed and treated in the authors' institution from 1 January 1996 to 31 December 1999 were reviewed retrospectively; 92 with metastatic prostate carcinoma were assessed (median age 71.0 years, range 42-93). Patients were included if they developed metastatic disease from prostate cancer at the time of diagnosis. The nadir for prostate specific antigen (PSA) level was defined as the date of the lowest PSA level after hormonal therapy, and AI was defined as the date of the third consecutive PSA increase above the nadir value by any threshold. RESULTS: The median Gleason sum was 8 and the modal Gleason score 4 + 5. The median (range) pretreatment PSA level was 274.0 (1.3-2179) ng/mL. Of the 92 men, 57 (62%) attained a nadir PSA, including 23 with a nadir of < 2 ng/mL; 32 (35%) progressed to AI within 2 years and 27% reached a nadir PSA but did not develop AI. The mean (sd) time from diagnosis to the nadir PSA was 13.7 (11.8) months, while the mean time from diagnosis to progression to AI was 30.3 (15.6) months. Univariate analysis showed that a nadir PSA level after treatment of >/= 1 ng/mL (P = 0.0128) was an early predictor of progression to AI; a nadir PSA level of >/= 2 ng/mL (P = 0.0216) was a predictor of poor overall survival. CONCLUSION: Failure to attain a nadir PSA of < 1 ng/mL after treatment predicts progression to AI and a nadir PSA of > 2 ng/mL predicts poorer overall survival. The development of skeletal events predicts the onset of AI but occurs late in the disease and is unsuitable as an early prognostic marker.     

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.     

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.     

Short-term outcome after high-intensity focused ultrasound in the treatment of patients with high-risk prostate cancer

OBJECTIVE: To assess the short-term outcome in patients with high-risk prostate cancer treated by transrectal high-intensity focused ultrasound (HIFU). PATIENTS AND METHODS: From April 2003 to November 2004, 30 patients with high-risk prostate cancer were enrolled in this prospective study; all had transurethral resection of the prostate before transrectal HIFU treatment, using the Ablatherm device (EDAP, Lyon, France) during the same session, associated with hormonal therapy with luteinizing hormone-releasing hormone analogues. After the procedure, all the patients were evaluated every 3 months by physical examination, prostate-specific antigen (PSA) assay and a continence questionnaire. The follow-up schedule also included a transperineal prostate biopsy 6 months after the treatment. All the patients had a minimum follow-up of 12 months. RESULTS: The HIFU treatment took a median (interquartile range, IQR) of 140 (100-160) min. No complications were reported during treatment. The mean (IQR) hospitalization was 2.2 (1-4) days, and the suprapubic drainage tube was removed after 12 (7-18) days. The complications after treatment were: urinary tract infections in five patients (16%), stenosis of the intraprostatic and membranous urethra in three (10%), and secondary infravesical obstruction in four (13%). At 12 months after the procedure, 28 patients (93%) were continent. Seven of the 30 men (23%) had a positive prostate biopsy. At the 1-year follow-up only three of the 30 patients with high-risk prostate cancer had a PSA level of >0.3 ng/mL. CONCLUSIONS: HIFU is a modern, minimally invasive therapy for prostate cancer, often used in selected patients with localized disease. The present results show that HIFU was also feasible in patients with high-risk prostate cancer. The low complication rates and favourable functional outcome support the planning of further larger studies in such patients. The oncological efficacy of HIFU should be assessed in further studies with a longer follow-up.     

Active surveillance; a reasonable management alternative for patients with prostate cancer: the Miami experience

OBJECTIVE

To examine the outcome of patients diagnosed with ‘low‐risk’ prostate cancer managed by active surveillance (AS).

PATIENTS AND METHODS

In all, 157 men with localized prostate cancer were followed on AS. The inclusion criteria for AS included: Gleason score of ≤ 6, a serum prostate‐specific antigen (PSA) level of ≤15 ng/mL, stage ≤ T2, low‐volume disease and >12 months of follow‐up. The follow‐up was rigorous, with PSA tests and a digital rectal examination every 3 months for 2 years, and a repeat biopsy 6–12 months after the initial diagnosis and yearly when indicated. Continuance of AS was based on the PSA doubling time, re‐biopsy score, Gleason score, tumour volume, stage progression and patient preference.

RESULTS

In all 99 patients met the inclusion criteria; their mean age at diagnosis was 66 years, their mean PSA level 5.77 ng/mL and the mean follow‐up 45.3 months. On initial repeat biopsy, 63% had no cancer and 34% had a Gleason sum of ≤ 6. Eight patients were treated (three with hormones; five with curative intent); two had radical prostatectomy (one had pT2c pNO Gleason 7 disease); three had radiotherapy. The probability is that 85% would remain treatment‐free at 5 years; no patient died from prostate cancer. The PSA doubling time and clinical stage at diagnosis were predictive of progression.

CONCLUSION

Patients who are followed on AS must be selected using narrowly defined inclusion criteria and closely followed with a standard regimen of PSA testing, digital rectal examination and repeat biopsy.     

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.     

前列腺癌近距离治疗的效果和不良反应分析

目的探讨局限性前列腺癌患者接受近距离治疗的疗效及不良反应。方法2001～2010年接受近距离治疗的局限性前列腺癌患者67例。随访术后PSA变化及不良反应发生情况，并分析影响治疗效果的相关因素。结果64例（95．5％）获得平均33．9（4～112）个月的随访。术前PSA平均为20．04ng／mL，术后最低PSA值平均为1．15ng／mL，40例（62．5％）患者最低PSA值〈1ng／mL，26例（40．6％）患者最低PSA值〈0．5ng／mL，达最低PSA值时间平均为术后11（1～26）个月。术后常见短期不良反应有：发热4例，血尿8例，便血3例。长期不良反应有：尿路刺激症状19例，便血7例，血尿2例，尿失禁2例，尿潴留1例。结论近距离治疗是局限性前列腺癌的有效治疗方法，疗效肯定，并发症发生率低，严重不良反应少见。