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.     

Rectal fistulae after salvage high‐intensity focused ultrasound for recurrent prostate cancer after combined brachytherapy and external beam radiotherapy

OBJECTIVE

To report on the high rectal fistula rate associated with salvage high‐intensity focused ultrasound (HIFU) after the failure of combined brachytherapy and external beam radiotherapy (EBRT) for prostate cancer; salvage ablative therapy for prostate cancer is indicated when there is local recurrence after RT, brachytherapy or their combination.

PATIENTS AND METHODS

We retrospectively reviewed all men with prostate cancer treated with HIFU between 1 March 2005 and 31 May 2007, and identified five men treated after the failure of both brachytherapy and EBRT for localized prostate cancer.

RESULTS

Three of the five men had iodine‐seed implantation brachytherapy combined with EBRT as primary treatment, one had high‐dose rate brachytherapy combined with EBRT and one had salvage iodine‐seed brachytherapy for failed EBRT. Three of the five patients developed a recto‐urethral fistula after HIFU.

CONCLUSIONS

The high rate of recto‐urethral fistula formation in this group might reflect an impaired blood supply or HIFU‐associated near‐field heating of the rectal wall. Tissue viability and healing might affect this group regardless of the salvage method. Careful patient selection and avoidance of rectal diagnostic biopsies might minimize the risk. Emerging ablative therapies regarded as less invasive than traditional therapies must be used with caution.     

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 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.     

Salvage permanent perineal radioactive‐seed implantation for treating recurrence of localized prostate adenocarcinoma after external beam radiotherapy

OBJECTIVE

To assess our experience with salvage permanent perineal radioactive‐seed implantation (SPPI) as a possible therapeutic option for recurrent prostate adenocarcinoma, as salvage therapies for recurrences after definitive external beam radiotherapy (EBRT) for localized adenocarcinoma of the prostate are associated with significant morbidity and biochemical failure.

PATIENTS AND METHODS

We retrospectively analysed on patients who had SPPI for localized recurrent prostate adenocarcinoma from 1996 to 2007 after primary treatment with EBRT. Excluded were patients who had other primary treatment or had no follow‐up. Primary outcomes were time to biochemical relapse‐free survival, using the Phoenix definition of a prostate‐specific antigen (PSA) nadir +2 ng/mL, and cancer‐specific survival. Secondary outcomes were the International Prostate Symptom Score (IPSS), the International Index of Erectile Function‐5 score (IIEF‐5), and complications based on Common Terminology Criteria for Adverse Events (version 3).

RESULTS

In all, 37 patients had SPPI during this period; after applying inclusion and exclusion criteria, 24 remained for analysis. At the time of salvage therapy, the median time to the diagnosis of local recurrence was 49 months, the median PSA level was 3.36 ng/mL, the median PSA doubling time was 20 months, and all patients were clinically re‐staged at ≤T2 with negative transrectal ultrasonography and/or magnetic resonance spectroscopy. The original Gleason score was ≤6 in nine patients, 7 in eight and ≥8 in three (not recorded in two). The median follow‐up after SPPI was 30 months; the cancer‐free survival was 96% (one death) and biochemical relapse‐free survival was 88% (three patients). The PSA level was higher than the levels before SPPI at 3 months in all three failures, but lower in all 21 patients considered relapse‐free. Complications included one urethral stricture, one grade 3 rectal haemorrhage and five grade 2 gross haematuria that resolved with conservative management. Insufficient data were available to assess the IPSS or IIEF‐5 scores.

CONCLUSION

With a short‐term follow‐up SPPI appears to provide excellent prostate cancer control with an acceptable rate of complications for patients with local recurrence of prostate cancer after EBRT. An extended follow‐up is necessary to determine the long‐term durability and safety of SPPI.     

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.

     

The feasibility and safety of high-intensity focused ultrasound as salvage therapy for recurrent prostate cancer following external beam radiotherapy

OBJECTIVES

To investigate the use of minimally invasive high‐intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT).

PATIENTS AND METHODS

A review of 31 cases treated using the Sonablate® 500 HIFU device, between 1 February 2005 and 15 May 2007, was carried out. All men had presumed organ‐confined, histologically confirmed recurrent prostate adenocarcinoma following EBRT.

RESULTS

The mean (range) age was 65 (57–80) years with a mean preoperative PSA level of 7.73 (0.20–20) ng/mL. The patients were followed for a mean (range) of 7.4 (3–24) months. Side‐effects included stricture or intervention for necrotic tissue in 11 of the 31 patients (36%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in two (7%). Recto‐urethral fistula occurred in two men, although one was due to patient movement due to inadequate anaesthesia, so the ‘true’ rate is 3%. Half of the patients had PSA levels of <0.2 ng/mL at the last follow‐up. Three patients had metastatic disease whilst another two had only local, histologically confirmed, failure. A further four patients had evidence of biochemical failure only. Overall, 71% had no evidence of disease following salvage HIFU.

CONCLUSIONS

Salvage HIFU is a minimally invasive daycase procedure that can achieve low PSA nadirs and good cancer control in the short term, with comparable morbidity to other forms of salvage treatment. The issue of accurate staging at the time of recurrence is still problematic, as a proportion of these men will harbour microscopic metastases undetected by conventional staging investigations.     

Prostate‐specific antigen relapse‐free survival and side‐effects in 734 patients with up to 10 years of follow‐up with localized prostate cancer treated by permanent 125iodine implants

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

OBJECTIVE

To report our analysis of the oncological outcome, side‐effects and complications after ¹²⁵I‐brachytherapy, based on 10 years of experience, as low dose‐rate (LDR) prostate brachytherapy is an accepted, effective and safe therapy for localized prostate cancer.

PATIENTS AND METHODS

Between April 1999 and December 2006, 734 consecutive patients were treated with clinically localized prostate cancer with a follow‐up of ≥30 months. No patients received external beam radiotherapy and 43% received hormonal therapy before brachytherapy; this therapy was given for 3–4 months. All patients had LDR prostate brachytherapy administered by one radiation oncologist. Biochemical failure was defined according to the ‘Phoenix consensus’.

RESULTS

The median follow‐up for the 734 patients was 55 months; 26 had a clinical relapse and 11 died from prostate cancer; 20 patients died from other illnesses. The 10‐year actuarial biochemical control was 92%, 84% and 65%, respectively (P < 0.001) for the low‐, intermediate‐ and high‐risk groups. Multivariate Cox regression analyses identified Gleason score and prostate‐specific antigen (PSA) level as independent prognostic factors for biochemical failure. The actuarial biochemical control with Gleason score was 88%, 76% and 67% for patients with a Gleason score of ≤6, 7 and >7, respectively (P < 0.001). The biochemical control was 90%, 80% and 42% for patients with a PSA level of ≤10, 10.1–20 and >20 ng/mL, respectively (P < 0.001). No patients reported incontinence after treatment. There was acute urinary retention in 22 (2.9%) patients. Logistic regression showed that the most significant factors correlating with the probability of catheterization were the pretreatment prostate volume and hormonal therapy.

CONCLUSIONS

The excellent long‐term results and low morbidity, and the many advantages of prostate brachytherapy over other treatments, show that brachytherapy is an effective treatment for clinically organ‐confined 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.

     

Salvage radiotherapy after high-intensity focused ultrasound treatment for localized prostate cancer: feasibility, tolerance and efficacy

Background:

The objective of this study is to evaluate the feasibility, tolerance and efficacy of salvage external beam radiotherapy (EBRT) in persistent or recurrent prostate cancer after failed high intensity focused ultrasound (HIFU) therapy.

Methods:

We reviewed data on tolerance and oncologic outcomes for all patients with biopsy-proven locally recurrent or persistent prostate cancer who underwent salvage EBRT in our department between April 2004 and June 2008. Minimum follow-up for inclusion was 2 years. Failure with EBRT was defined as biochemical relapse (Phoenix definition) or introduction of androgen deprivation therapy (ADT). Gastrointestinal and urinary toxicity and urinary stress incontinence were scored at 12 and 24 months (Radiation Therapy Oncology Group and Ingelman Sundberg rating, respectively).

Results:

The mean age of the patients was 68.8 years (range: 60–79). Mean prostate-specific antigen (PSA) before EBRT was 5.57 ng/mL (range: 2.5–14.8). Median follow-up was 36.5 ± 10.9 months (range: 24–54). No patient received adjunctive ADT. The EBRT course was well-tolerated and completed by all patients. The mean PSA nadir was 0.62 ng/mL (range: 0.03–2.4) and occurred after a median of 22 months (range: 12–36). One patient experienced biochemical failure and was prescribed ADT 30 months after EBRT. The disease-free survival rate was 83.3% at 36.5 months. There was no major EBRT-related toxicity at 12 or 24 months.

Conclusions:

Our early clinical results confirm the feasibility and good tolerance of salvage radiotherapy after HIFU failure. Oncological outcomes were promising. A prospective study with longer follow-up is needed to identify factors predictive of success for salvage EBRT therapy after HIFU failure.     

Salvage robotic‐assisted radical prostatectomy: initial results and early report of outcomes

OBJECTIVE

To evaluate the initial results of salvage robotic‐assisted radical prostatectomy (SRARP) after recurrence following primary radiotherapy (RT) for localized prostate cancer.

PATIENTS AND METHODS

Between December 2002 and January 2008, 11 patients had SRARP with pelvic lymph node dissection by one surgeon from one institution. Six patients had brachytherapy, three had external beam RT (EBRT), one intensity‐modulated RT, and one received brachytherapy with an EBRT boost. All patients had prostate cancer on biopsy after RT, with negative computed tomography and bone scan. The mean (range) follow‐up was 20.5 (1–77) months.

RESULTS

The mean interval from RT to SRARP was 53.2 months; the mean preoperative prostate‐specific antigen (PSA) level was 5.2 ng/mL, the operative duration 183 min and the estimated blood loss 113 mL. One patient had prolonged lymphatic drainage, one had an anastomotic leak, and one had an anastomotic stricture requiring direct vision internal urethrotomy at 3 months. The mean duration of catheterization was 10.4 days and the hospital stay 1.4 days. Three patients had a biochemical recurrence, at 1, 2 and 43 months. In one of two patients with node‐positive carcinoma of the prostate the PSA level failed to reach a nadir of zero after surgery. In patients with a minimum follow‐up of 2 months, eight of 10 are continent (defined as zero to one pad per day) and two have erections adequate for intercourse with the use of phosphodiesterase‐5 inhibitors.

CONCLUSION

SRARP after RT‐resistant disease recurrence is feasible with minimal perioperative morbidity. Early functional outcomes appear to be at least equivalent with historical salvage RP series. Robotic extended pelvic lymph node dissection is safe and can improve the accuracy of surgical staging. A longer follow‐up is necessary to better assess the functional and oncological outcomes.     

Primary whole‐gland ablation for localized prostate cancer with high‐intensity focused ultrasound: The important predictors of biochemical recurrence

Objectives

To identify predictive factors of biochemical recurrence for patients undergoing high‐intensity focused ultrasound treatment for localized prostate cancer.

Methods

We retrospectively identified patients receiving whole‐gland prostate ablation with high‐intensity focused ultrasound for localized prostate cancer from 2009 to 2015. All the patients received pre‐high‐intensity focused ultrasound radical transurethral resection of the prostate. We included perioperative parameters as follows: age, preoperative prostate volume, stage of operation, initial prostate‐specific antigen, T stage, postoperative prostate‐specific antigen nadir, Gleason score, time to prostate‐specific antigen nadir and the presence of prostate‐specific antigen biochemical recurrence. Multivariable Cox regression and Kaplan–Meier analysis were used for investigating predictors of recurrence, and receiver operating characteristic analysis was used for the cut‐off values of prostate‐specific antigen nadir.

Results

Among 182 patients, 26.9% had prostate‐specific antigen biochemical recurrence after high‐intensity focused ultrasound during the median follow‐up period of 32.21 months. Gleason score ≥7 (Gleason score 7, hazard ratio 2.877, P = 0.027), stage ≥T2b (T2b, hazard ratio 3.16, P = 0.027) and prostate‐specific antigen nadir (hazard ratio 1.11, P < 0.001) were statistically significant, whereas there was no significance in prostate volume and initial prostate‐specific antigen. We posit that a cut‐off level of prostate‐specific antigen nadir 0.43 ng/mL might be considered as an independent predictive factor for prostate‐specific antigen biochemical recurrence in high‐intensity focused ultrasound patients in multivariate analysis (P < 0.001, hazard ratio 7.39, 95% confidence interval 3.56–15.37), and created a new nadir‐related prediction model for biochemical recurrence prediction.

Conclusions

Postoperative prostate‐specific antigen nadir of 0.43 ng/mL can be considered an important predictive factor for biochemical recurrence in primary whole‐prostate gland high‐intensity focused ultrasound treatment, and the nadir‐related prediction model might provide a reference for early salvage treatment. Furthermore, Gleason score ≥7, stage ≥T2b might be associated with unfavorable outcomes, although prostate volume and higher initial prostate‐specific antigen appear not to be associated with biochemical recurrence for the high‐intensity focused ultrasound treatment.

     

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.     

Current salvage methods for recurrent prostate cancer after failure of primary radiotherapy

We reviewed the current salvage methods for patients with local recurrent prostate cancer after primary radiotherapy (RT), using a search of relevant Medline/PubMed articles published from 1982 to 2008, with the following search terms: ‘radiorecurrent prostate cancer, local salvage treatment, salvage radical prostatectomy (RP), salvage cryoablation, salvage brachytherapy, salvage high‐intensity focused ultrasound (HIFU)’, and permutations of the above. Only articles written in English were included. The objectives of this review were to analyse the eligibility criteria for careful selection of appropriate patients and to evaluate the oncological results and complications for each method. There are four whole‐gland re‐treatment options (salvage RP, salvage cryoablation, salvage brachytherapy, salvage HIFU) for RT failure, although others might be in development or investigations. Salvage RP has the longest follow‐up with acceptable oncological results, but it is a challenging technique with a high complication rate. Salvage cryoablation is a feasible option, especially using third‐generation technology, whereby the average biochemical disease‐free survival rate is 50–70% and there are fewer occurrences of severe complications such as recto‐urethral fistula. Salvage brachytherapy, with short‐term cancer control, is comparable to other salvage methods but depends on cumulative dosage limitation to target tissues. HIFU is a relatively recent option in the salvage setting. Both salvage brachytherapy and HIFU require more detailed studies with intermediate and long‐term follow‐up. As these are not prospective, randomized studies and the definitions of biochemical failure varied, there are limited comparisons among these different salvage methods, including efficacy. In the focal therapy salvage setting, the increased use of thermoablative methods for eligible patients might contribute to reducing complications and maintaining quality of life. The problem to effectively salvage patients with locally recurrent disease after RT is the lack of diagnostic examinations with sufficient sensitivity and specificity to detect local recurrence at an early curable stage. Therefore, a more strict definition of biochemical failure, improved imaging techniques, and accurate specimen mapping are needed as diagnostic tools. Furthermore, universal selection criteria and an integrated definition of biochemical failure for all salvage methods are required to determine which provides the best oncological efficacy and least comorbidity.     

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   

Pathological results and rates of treatment failure in high‐risk prostate cancer patients after radical prostatectomy

Study Type – Therapy (outcomes research) Level of Evidence 2b What’s known on the subject? and What does the study add? In the current literature, cT3 stage, biopsy Gleason > 8, PSA > 20 ng/ml, and D’Amico high‐risk category are frequently used definitions of high‐risk prostate cancer. Patients with clinically localized high‐risk prostate cancer do not have a uniformly poor prognosis after surgery. The rates of favourable pathological characteristics and biochemical‐recurrence free survival vary depending on the definition used for high‐risk prostate cancer.

OBJECTIVE

? To investigate the pathological characteristics and the rates of biochemical recurrence (BCR) ‐free survival after radical prostatectomy (RP) in men with high‐risk prostate cancer.

METHODS

? Of 4760 patients treated with RP for prostate cancer at three institutions, 293 patients (6.2%) had clinical stage T3, 269 (5.7%) had a biopsy Gleason sum ≥ 8, 370 (7.8%) had preoperative PSA ≥ 20 ng/mL and 887 (18.6%) were considered high‐risk according to the D’Amico classification (clinical stage ≥ T2c or prostate‐specific antigen (PSA) ≥ 20 ng/mL or biopsy Gleason sum ≥ 8). ? Actuarial BCR‐free survival probabilities after RP and the rate of favourable pathology (organ‐confined cancer, negative surgical margin and Gleason ≤ 7) were assessed.

RESULTS

? Median follow up was 2.4 years and 1179 (24.8%) patients had follow up beyond 5 years. ? The rate of favourable pathology increased in the following order: clinical stage T3 (13.7%), biopsy Gleason ≥ 8 (16.4%), the D’Amico high‐risk group (21.4%) and PSA ≥ 20 ng/mL (21.6%). ? The 5‐year BCR‐free survival probabilities were 35.4% for Gleason ≥ 8, 39.8% for PSA ≥ 20 ng/mL, 47.4% for D’Amico high‐risk group and 51.6% for clinical stage T3. ? Patients with only one risk factor had the most favourable 5‐year BCR‐free survival (50.3%), relative to patients with two or more risk factors (27.5%)

CONCLUSIONS

? Men with clinically localized high‐risk prostate cancer do not have a uniformly poor prognosis after RP. ? The rate of favourable pathology and of BCR‐free survival may vary substantially, depending on the definition used. ? RP should be considered a valid treatment modality for high‐risk prostate cancer patients, as many can be surgically down‐staged.     

The Role of Cryosurgery of the Prostate for Nonsurgical Candidates

Introduction:

Technological advancements have reduced the morbidity associated with cryosurgery, leading to an increased interest in this modality for the treatment of organ-confined prostate cancer. In this study, we critically examine the current role of cryoablation of the prostate to better understand how to counsel patients regarding this treatment option.

Methods:

A database was compiled over a 3-year period (2008–2011) of 30 patients who underwent cryoablation for organ-confined prostate cancer. Indications for cryosurgery included primary treatment, focal treatment (institutional review board–approved prospective study), and salvage cryotherapy for radiation failure. The primary outcomes were biochemical response via prostate-specific antigen (PSA) measurement and morbidity associated with cryoablation. Cryotherapy failure was defined as an increasing postcryotherapy PSA level ≥ 2 ng/mL above the post-treatment nadir, a positive prostate biopsy, or radiographic evidence of metastatic disease.

Results:

Of the 30 patients who underwent cryoablation from 2008 to 2011, 26 patients had complete follow-up data for analysis. Of these patients, 17 (65.38%) had total gland cryotherapy, 5 (19.23%) had salvage cryotherapy for radiation failure, and 4 (15.38%) had focal cryotherapy. The mean patient age was 68 years (54–89); median preoperative PSA was 5.5 ng/mL (1.7–15.9); median prostate volume was 35 mL (15–54); mean Gleason score was 7; and the median PSA at study conclusion was 0.7 (0.02–3.4) ng/mL. Of the 17 patients who had total prostate cryotherapy, 11 (64.7%) had significant factors precluding primary treatment by a surgical and/or radiation approach, including neurological disorders (2), morbid obesity (1), rectal cancer treated with radiation (1), kidney/pancreas transplant (2), ileoanal pouch secondary to inflammatory bowel disease (IBD) (1), renal failure (1), and age (3).There were no intra- or postoperative complications. After a median follow-up of 18 months (1–40), none of the patients with multiple comorbidities had biochemical failures. Two patients from the salvage group experienced treatment failure requiring androgen deprivation therapy.

Conclusions:

This critical analysis of a single-surgeon experience at a large academic prostate cancer program revealed that the contemporary role of cryosurgery is, in select patients with comorbidities, preventing surgical and/or radiation therapy. Additionally, cryosurgery has a role in treating radiation failures. Further studies are necessary to investigate focal cryotherapy as an option for primary treatment, but our preliminary results are promising, without any biochemical failures in our focal therapy cohort.     

Oncological impact of neoadjuvant hormonal therapy on permanent iodine‐125 seed brachytherapy in patients with low‐ and intermediate‐risk prostate cancer

Objectives

To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy.

Methods

Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography‐guided permanent iodine‐125 seed brachytherapy. We retrospectively analyzed low‐ or intermediate‐risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence‐free survival, progression‐free survival, cancer‐specific survival and overall survival.

Results

A total of 484 patients with low‐risk (259 patients) or intermediate‐risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5‐year actuarial biochemical recurrence‐free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence‐free survival outcomes in low‐ (P = 0.8949) or intermediate‐risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate‐specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence‐free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression‐free survival, cancer‐specific survival or overall survival.

Conclusions

In patients with low‐ or intermediate‐risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.