High-intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: predictors of disease response.

BACKGROUND: Some men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort. MATERIALS AND METHODS: Patients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence. Exclusion criteria included the receipt of prior salvage therapy, presence of metastatic disease, and administration of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary endpoint was recurrence-free survival (RFS), defined as a composite endpoint of PSA progression (Phoenix criteria), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (TRUS biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and receipt of prior hormone therapy). Survival analysis was performed on participants with a minimum of 1-year follow-up. RESULTS: Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04ng/ ml. Median 2-year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 pre-specified predictors, an undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant underwent an intervention for a urethral stricture. No participants developed osteitis pubis or rectourethral fistulae. CONCLUSIONS: Salvage HIFU allows for disease control in selected patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.

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

UNLABELLED: 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 (Q(1):0, Q(3):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.

How to use an article about therapy.

PURPOSE: Most surgical interventions have inherent benefits and associated risks. Before implementing a new therapy we should ascertain the benefits and risks of the therapy and assure ourselves that the resources consumed in the intervention will not be exorbitant. MATERIALS AND METHODS: We suggest a 3-step approach to using an article from the urological literature to guide patient care. We recommend asking whether the study can provide valid results, reviewing the results and considering how the results can be applied to patient care. RESULTS: Key methodological characteristics that have an impact on the validity of a surgical trial include randomization, allocation concealment, stratification, blinding, completeness of followup and intent to treat analysis. To the extent that the quality is poor inferences from this study are weakened. However, if its quality is acceptable, one must determine the range within which the true treatment effect lies (95% CI). One must then consider whether this result can be generalized to a patient and whether the investigators have provided information about all clinically important outcomes. It is then necessary to compare the relative benefits of the intervention with its risks. If one perceives that the benefits outweigh the risks, the intervention may be of use to the patient. CONCLUSIONS: Given the time constraints of busy urological practices and training programs, applying this analysis to every relevant article would be challenging. However, the basics of this process are essentially what we all do hundreds of times each week when treating patients. Making this process explicit with guidelines to assess the strength of the available evidence will serve to improve patient care. It will also allow us to defend therapeutic interventions based on available evidence and not on anecdote.

Measuring the minimum clinically important difference in BPH outcome measures.

PURPOSE: To determine the minimum clinically important difference with respect to the different outcome measures used in benign prostatic hyperplasia (BPH) research. MATERIALS AND METHODS: Forty-two patients diagnosed with symptomatic BPH were prospectively recruited from community urology clinics. Patients were asked at follow-up visits to rate their improvement using a self-administrated questionnaire. The improvement score was then compared to the changes from baseline in each of the outcome measures. RESULTS: Maximum and mean flow-rates did not correlate significantly with the patient's improvement measure. The Boyarsky score correlated best with the patient's grading of overall improvement (R=.507, p<.001). The mean change in Boyarsky symptom score for patients with a small improvement was 3.23 (sd=3.52).

High-Intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: predictors of disease response

ABSTRACT Background Some men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort. Materials and Methods Patients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence. Exclusion criteria included the receipt of prior salvage therapy, presence of metastatic disease, and administration of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary endpoint was recurrence-free survival (RFS), defined as a composite endpoint of PSA progression (Phoenix criteria), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (TRUS biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and receipt of prior hormone therapy). Survival analysis was performed on participants with a minimum of 1-year follow-up. Results Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04ng/ml. Median 2-year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 prespecified predictors, an undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant underwent an intervention for a urethral stricture. No participants developed osteitis pubis or rectourethral fistulae. Conclusions Salvage HIFU allows for disease control in selected patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.

A cost-analysis comparison of laparoscopic radical prostatectomy versus open radical prostatectomy: the McMaster Institute of Urology experience.

INTRODUCTION: The objective of this study was to identify and compare the costs of laparoscopic radical prostatectomy (LRP) and radical retropubic prostatectomy (RRP) at our centre. METHODS: We conducted a retrospective chart review of our first 70 consecutive LRP cases and 70 consecutive RRP cases at St. Joseph's Healthcare in Hamilton, Ontario, Canada. We performed cost analysis, including operating room costs, disposable instruments, blood transfusions, analgesic requirements and length of hospital stay. Overall expenses were then analyzed and compared. RESULTS: Preoperative patient demographics and disease stages were comparable between the LRP and RRP groups. On a per procedure basis, large discrepancies were found in mean disposable instrument costs (LRP = $659.18 vs. RRP = $236.59), operating room costs (LRP = $4278.00 vs. RRP = $3139.00), mean cost of blood transfusions (LRP = $21.00 vs. RRP = $394.34), mean analgesia requirements (LRP = $12.94 vs. RRP = $41.06) and mean hospital stay bed costs (LRP = $3690.00 vs. RRP = $5027.14). Overall, costs for all patients in the LRP and RRP groups, respectively, were $606 307.29 and $618 721.57 with a cost saving of $12 414.28 in favour of the LRP arm. CONCLUSION: At our institution, we found that LRP costs are slightly less than those for RRP. Higher operative time and disposable instrument expenses are offset by the shorter hospital stays, fewer blood transfusions and less analgesic requirements for the LRP group. Further financial advantages for LRP will likely be achieved with additional reduction of operating room time and by minimizing disposables.