Abstract Background Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing ...interest as an alternative to radical treatment of low-risk PCa. Objective To update our experience in the largest worldwide prospective AS cohort. Design, setting, and participants Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤6. PSA was measured every 3–6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. Outcome measurements and statistical analysis Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy–free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. Results and limitations In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. Conclusions Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized. Trial registration The current program is registered at the Dutch Trial Register with ID NTR1718 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718 ).
Objective
To report the oncological outcome of salvage high‐intensity focused ultrasound (S‐HIFU) for locally recurrent prostate cancer after external beam radiotherapy (EBRT) from a multicentre ...database.
Patients and Methods
This retrospective study comprises patients from nine centres with local recurrent disease after EBRT treated with S‐HIFU from 1995 to 2009. The biochemical failure‐free survival (bFFS) rate was based on the ‘Phoenix’ definition (PSA nadir + 2 ng/mL). Secondary endpoints included progression to metastasis and cancer‐specific death. Kaplan–Meier analysis was performed examining overall (OS), cancer‐specific (CSS) and metastasis‐free survival (MFS). Adverse events and quality of life status are reported.
Results
In all, 418 patients with a mean (SD) follow‐up of 3.5 (2.5) years were included. The mean (SD) age was 68.6 (5.8) years and the PSA level before S‐HIFU was 6.8 (7.8) ng/mL. The median PSA nadir after S‐HIFU was 0.19 ng/mL. The OS, CSS and MFS rates at 7 years were 72%, 82% and 81%, respectively. At 5 years the bFFS rate was 58%, 51% and 36% for pre‐EBRT low‐, intermediate‐ and high‐risk patients, respectively. The 5‐year bFFS rate was 67%, 42% and 22% for pre‐S‐HIFU PSA level ≤4, 4–10 and ≥10 ng/mL, respectively. Complication rates decreased after the introduction of specific post‐RT parameters: incontinence (grade II or III) from 32% to 19% (P = 0.002); bladder outlet obstruction or stenosis from 30% to 15% (P = 0.003); recto‐urethral fistula decreased from 9% to 0.6% (P < 0.001). Study limitations include being a retrospective analysis from a registry with no control group.
Conclusion
S‐HIFU for locally recurrent prostate cancer after failed EBRT is associated with 7‐year CSS and MFS rates of >80% at a price of significant morbidity. S‐HIFU should be initiated early following EBRT failure
OBJECTIVES
To compare the specificity and sensitivity of different definitions of biochemical failure in patients treated with high‐intensity focused ultrasound (HIFU) for prostate cancer, to ...identify the most accurate predictor of clinical failure after HIFU.
PATIENTS AND METHODS
Consecutively treated patients who underwent HIFU between October 1997 and July 2006 at two centres (Lyon, France; and Regensburg, Germany) were prospectively maintained within a central database and retrospectively reviewed for this study. Clinical failure was defined as a positive prostate biopsy after treatment, radiographic evidence of lymphatic or bony metastatic disease, or salvage treatment for prostate cancer (surgery, radiation, hormonal therapy or second HIFU). The serum prostate‐specific antigen (PSA) values after HIFU were assessed as a biochemical surrogate of a therapeutic success or failure. PSA threshold values, ‘PSA nadir plus’, PSA velocity, PSA doubling time and the American Society or Therapeutic Radiotherapy and Oncology and Phoenix definition of biochemical failure were all considered. The sensitivity, specificity, positive predictive value and negative predictive value of each biochemical definition for predicting clinical failure were determined.
RESULTS
The data from 285 patients (stage ≤ T2, PSA <15 ng/mL, Gleason score ≤7) were analysed. The median (range) follow‐up was 4.7 (2–10.9) years. The median PSA nadir was 0.13 ng/mL, which occurred at a median of 12.9 weeks after HIFU, and the median PSA at the last follow‐up was 0.76 (1.6–2.7) ng/mL. Clinical failure occurred in 71 patients (25%); 24 due to a positive biopsy and 47 through the use of an additional therapy. Biochemical events that best predicted clinical failure were ‘PSA nadir plus’ values of 1.1–1.3 ng/mL, PSA velocities of <0.3 ng/mL/year and PSA doubling times of 1.25–1.75 years.
CONCLUSION
A new definition of biochemical failure that is specific to patients treated with HIFU therapy is established, i.e. the ‘Stuttgart definition’, the ‘PSA nadir plus 1.2 ng/mL’.
Study Type – Prognosis (retrospective cohort)
Level of Evidence 2b
What’s known on the subject? and What does the study add?
The prostate‐specific antigen (PSA) nadir after high‐intensity focused ...ultrasound (HIFU) therapy for clinically localized prostate cancer has been shown to correlate with treatment failure in single centre studies. Purpose was to determine if the PSA nadir after HIFU can be used as a predictor of the biochemical disease‐free survival in a multicentre study.
This multicentre analysis confirms that PSA nadir after HIFU predicts biochemical DFSR in a statistically significant manner.
OBJECTIVE
• To determine if the prostate‐specific antigen (PSA) nadir after high‐intensity focused ultrasound (HIFU) can be used as a predictor of the biochemical disease‐free survival rate (DFSR).
PATIENTS AND METHODS
• Patient data were derived from the multicentre‐based @‐Registry, the largest registry to report outcomes in patients with localized prostate cancer after Ablatherm® HIFU.
• PSA level was measured at 3‐month intervals. Patients were stratified into four PSA nadir groups: group 1, ≤0.2 ng/mL; group 2, 0.21–0.5 ng/mL; group 3, 0.51–1 ng/mL; and group 4, >1 ng/mL.
• Biochemical treatment failure was defined according to the Stuttgart definition (PSA nadir + 1.2 ng/mL) and the Phoenix definition (PSA nadir + 2 ng/mL).
• Biopsy was performed at 3–6 months post‐HIFU or if a PSA level was recorded that was considered clinically relevant.
RESULTS
• The present study included 804 patients. Biochemical treatment success rates at 5 years according to the Stuttgart definition for the four PSA nadir sub‐groups were as follows: 84, 64, 40 and 30% for groups 1–4, respectively.
• The equivalent 5‐year biochemical success rates using the Phoenix definition were 94, 74, 66 and 47%, respectively.
• Significantly more patients had a negative biopsy in the lowest PSA nadir group than in the other sub‐groups (91.6 vs 73.1%; P < 0.001).
• The present study is limited by its retrospective nature and variations in clinical practice across participating centres.
CONCLUSION
• This multicentre analysis confirms that PSA nadir after HIFU predicts biochemical DFSR in a statistically significant manner.
This study analyzes patient health-related quality of life (QoL) 24-month after prostate cancer (PCa) diagnosis within the PROState cancer monitoring in ITaly from the National Research Council ...(Pros-IT CNR) study.
Pros-IT CNR is an ongoing, longitudinal and observational study, considering a convenience sample of patients enrolled at PCa diagnosis and followed at 6, 12, 24, 36, 48 and 60 months from the diagnosis. Patients were grouped according to the treatment received: nerve sparing radical prostatectomy (NSRP), non-nerve sparing radical prostatectomy (NNSRP), radiotherapy (RT), RT plus androgen deprivation (RT plus ADT) and active surveillance (AS). QoL was measured through the Italian versions of SF-12 and UCLA-PCI questionnaires at diagnosis and at 6-12 and 24-month. The minimal clinically important difference (MCID) was defined as half a standard deviation of the baseline domain.
Overall, 1537 patients were included in the study. The decline in urinary function exceeded the MCID at each timepoint only in the NSRP and NNSRP groups (at 24 months -14.7, P<0.001 and -19.7, P<0.001, respectively). The decline in bowel function exceeded the MCID only in the RT (-9.1, P=0.02) and RT plus ADT groups at 12 months (-10.3, P=0.001); after 24 months, most patients seem to recover their bowel complaints. The decline in sexual function exceeded the MCID at each timepoint in the NNSRP, NSRP and RT plus ADT groups (at 6 months -28.7, P<0.001, -37.8, P<0.001, -20.4, P<0.001, respectively).
Although all the treatments were relatively well-tolerated over the 24 month period following PCa diagnosis, each had a different impact on QoL.
Prostate cancer (PCa) is the second most common neoplasm in male patients. To date, there's no certain indication about the maximum waiting time (WT) acceptable for treatment beginning and the impact ...on oncological and functional outcomes has not been well established.
Data from the National Research Council PCa monitoring multicenter project in Italy (Pros-IT CNR) were prospectively collected and analyzed. WT was defined as the time from the bioptical diagnosis of PCa to the first treatment received. Patients were divided in two groups, using a time frame of 90 days. Quality of life was measured through the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and of the Short-Form Health Survey (SF-12). The occurrence of upgrading, upstaging, presence of lymph node metastasis and positive surgical margins at the final histopathological diagnosis, and PSA at 12 months follow-up were evaluated.
The overall median WT was 93 days. The logistic multivariable model confirmed that age, being resident in Southern regions of Italy and T staging at diagnosis were significantly associated with a WT>90 days. At 6 months from diagnosis the mean SF-12 score for the emotional-psychological component was significantly lower in WT≥90 days group (P=0.0428). Among patients treated with surgical approach, no significant differences in oncological outcomes were found in the two groups.
In our study age, clinical T stage and provenance from Southern regions of Italy are associated with a WT>90 days. WT might have no impact on functional and oncological outcome.
Study Type - Prognosis (retrospective cohort) Level of Evidence2b What's known on the subject? and What does the study add? The prostate-specific antigen (PSA) nadir after high-intensity focused ...ultrasound (HIFU) therapy for clinically localized prostate cancer has been shown to correlate with treatment failure in single centre studies. Purpose was to determine if the PSA nadir after HIFU can be used as a predictor of the biochemical disease-free survival in a multicentre study. This multicentre analysis confirms that PSA nadir after HIFU predicts biochemical DFSR in a statistically significant manner. times To determine if the prostate-specific antigen (PSA) nadir after high-intensity focused ultrasound (HIFU) can be used as a predictor of the biochemical disease-free survival rate (DFSR). times Patient data were derived from the multicentre-based at-Registry, the largest registry to report outcomes in patients with localized prostate cancer after Ablatherm registered HIFU. times PSA level was measured at 3-month intervals. Patients were stratified into four PSA nadir groups: group 1, less than or equal to 0.2ng/mL; group 2, 0.21-0.5ng/mL; group 3, 0.51-1ng/mL; and group 4, >1ng/mL. times Biochemical treatment failure was defined according to the Stuttgart definition (PSA nadir + 1.2ng/mL) and the Phoenix definition (PSA nadir + 2ng/mL). times The present study included 804 patients. Biochemical treatment success rates at 5 years according to the Stuttgart definition for the four PSA nadir sub-groups were as follows: 84, 64, 40 and 30% for groups 1-4, respectively. times The equivalent 5-year biochemical success rates using the Phoenix definition were 94, 74, 66 and 47%, respectively. times Significantly more patients had a negative biopsy in the lowest PSA nadir group than in the other sub-groups (91.6 vs 73.1%; P < 0.001). times The present study is limited by its retrospective nature and variations in clinical practice across participating centres. times This multicentre analysis confirms that PSA nadir after HIFU predicts biochemical DFSR in a statistically significant manner.Original Abstract: times Biopsy was performed at 3-6 months post-HIFU or if a PSA level was recorded that was considered clinically relevant.
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