Phoenix Definition Of Biochemical Failure Research Articles

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old-Updated Results.

Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports updated outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. Between April 2006 and December 2022, 6,130 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator. Information was available for 4,143 patients. 3568 (86.12%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 575 (13.88%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 1,035 (24.98%) of these cases. The mean age was 67.4 years old. 48 patients were younger than 50 years old (mean age 46.6). 4,095 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 43.75%, 50.00%, 6.25% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 23.88%, 57.05%, 19.07% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 47.92%, 7 in 47.92%, and 8-10 in 4.16%. 44 younger patients were treated with SBRT alone. 4 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.42%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 29.84%, 7 in 54.14%, and 8-10 in 16.02%. 3522 were treated with SBRT alone. 573 patients also received supplemental external beam radiation (median dose 4500cGY) and 1030 patients (25.15%) received Androgen Deprivation Therapy (ADT) as part of their treatment. At 75 months the 6-year biochemical relapse free survival was 95.83% in younger patients compared to 98.41% in older patients using the Phoenix definition of biochemical failure. The 6-year median post treatment PSA was 0.3 in younger patients and 0.2 in the older patients. There were no significant differences in the risk stratification between the 2 groups. This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With updated 6-year follow up, SBRT remains an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old

Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients.Between April 2006 and December 2020, 3626 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator and followed at an academic institution. 3173 (87.51%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 453 (12.49%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 865 (23.86%) of these cases. The mean age was 67.3 years old. 47 patients were younger than 50 years old (mean age 46.6). 3,579 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 44.68%, 48.94%, 6.38% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 24.76%, 56.83%, 18.41% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 48.94%, 7 in 46.81%, and 8-10 in 4.25%. 44 younger patients were treated with SBRT alone. 3 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.6%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 30.57%, 7 in 54.06%, and 8-10 in 15.37%. 3129 were treated with SBRT alone. 450 patients also received supplemental external beam radiation (median dose 4500cGY) and 860 patients (24.03%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen.At 64.8 months (range 7 months - 177 months) the 5-year biochemical relapse free survival was 98% in younger patients compared to 99% in older patients using the Phoenix definition of biochemical failure. The 5-year median post treatment PSA was 0.15 in the younger patients and 0.20 in the older patients. There were no significant differences in biochemical relapse free survival between the groups.This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With 5-year follow up, SBRT is an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Radiobiological parameters in a tumour control probability model for prostate cancer LDR brachytherapy

To provide recommendations for the selection of radiobiological parameters for prostate cancer treatment planning. Recommendations were based on validation of the previously published values, parameter estimation and a consideration of their sensitivity within a tumour control probability (TCP) model using clinical outcomes data from low-dose-rate (LDR) brachytherapy.The proposed TCP model incorporated radiosensitivity (α) heterogeneity and a non-uniform distribution of clonogens. The clinical outcomes data included 849 prostate cancer patients treated with LDR brachytherapy at four Australian centres between 1995 and 2012. Phoenix definition of biochemical failure was used. Validation of the published values from four selected literature and parameter estimation was performed with a maximum likelihood estimation method. Each parameter was varied to evaluate the change in calculated TCP to quantify the sensitivity of the model to its radiobiological parameters.Using a previously published parameter set and a total clonogen number of 196 000 provided TCP estimates that best described the patient cohort. Fitting of all parameters with a maximum likelihood estimation was not possible. Variations in prostate TCP ranged from 0.004% to 0.67% per 1% change in each parameter. The largest variation was caused by the log-normal distribution parameters for α (mean, , and standard deviation, σα).Based on the results using the clinical cohort data, we recommend a previously published dataset is used for future application of the TCP model with inclusion of a patient-specific, non-uniform clonogen density distribution which could be derived from multiparametric imaging. The reduction in uncertainties in these parameters will improve the confidence in using biological models for clinical radiotherapy planning.

Comparison of Biochemical and Toxicity Outcomes From a Contemporaneous Cohort Study of Low-Risk Prostate Cancer Treated With Different Radiation Techniques

Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is an emerging radiation therapy technique that appears to be efficacious, well tolerated and convenient. However, outcomes for patients treated with SBRT are unknown compared to more conventional radiation options for patients with prostate cancer. The purpose of this study is to evaluate and compare late toxicities and biochemical disease-free survival (bDFS) of low risk prostate cancer patients (T1-T2b, PSA 10 ng/mL, and Gleason Sum 6) treated SBRT (35 Gy/5 fractions), standard external beam radiation therapy (STND; median 76 Gy/38 fractions) or low-dose brachytherapy (LDR; iodine-125, 145 Gy). Materials/Methods: Consecutive patients with low risk prostate cancer treated with radiation from 2006-2008 were analyzed. Patients treated with SBRTwere part of a phase 2 prospective clinical trial; patients treated with STND or LDR had data abstracted from paper and electronic medical charts retrospectively. Patients treated with neoadjuvant androgen deprivation therapy were excluded from biochemical analyses. The Phoenix definition (nadir + 2 ng/mL) was used to define biochemical failure. Fisher exact test or Kruskal-Wallis test was applied for comparing treatment groups on covariates. Univariate (UVA) and multivariate analyses (MVA) of Cox proportional hazard model were conducted to identify significant covariates predicting bDFS. Results: A total of 357 low-risk prostate cancer patients were identified (84 SBRT, 81 STND, and 192 LDR). The median follow-up was 57, 62, and 59 months, respectively. At baseline, 85% of patients were T1c, 15% T2a; 100% had GS 6; median PSA 5.9 ng/mL. There were more patients in the STND and LDR cohort who had T2a disease (6% in SBRT, 21% in STND and 16% in LDR, p Z 0.013) and the mean PSA was higher in the STND cohort (6.08 in SBRT, 6.69 in STND, and 6.02 in LDR, pZ 0.017). Patients who received LDR experienced more late hematuria (0% in SBRT, 1.23% in STND and 11.98% in LDR, p < 0.0001); otherwise there were no significant differences in late toxicities observed. Ten patients reached the Phoenix definition of biochemical failure (6 in LDR, 2 in STND, and 2 in SBRT). There were no significant differences in bDFS (97.4% in SBRT vs 96.9% in STND vs 97.2% in LDR at 60 months, p Z 0.94). There were no covariates identified predicting bDFS on UVA or MVA, including treatment type. Conclusions: SBRT, STND and LDR show equivalent effectiveness at our center and both external beam techniques showed less hematuria than LDR. However, SBRT and LDR are more convenient and less costly than STND. Further prospective studies of SBRT are ongoing. Author Disclosure: D. Loblaw: None. P. Sethukavalan: None. P. Cheung: None. G. Morton: None. L. D’Alimonte: None. A. Deabreu: None. A. Mamedov: None. L. Zhang: None. H. Chung: None. R. Nam: None.

Long term results of a prospective dose escalation phase-II trial: Interstitial pulsed-dose-rate brachytherapy as boost for intermediate- and high-risk prostate cancer

PurposeWe reviewed our seven year single institution experience with pulsed dose rate brachytherapy dose escalation study in patients with intermediate and high risk prostate cancer. Materials and methodsWe treated a total of 130 patients for intermediate and high risk prostate cancer at our institution between 2000 and 2007 using PDR-brachytherapy as a boost after conformal external beam radiation therapy to 50.4Gy. The majority of patients had T2 disease (T1c 6%, T2 75%, T3 19%). Seventy three patients had intermediate-risk and 53 patients had high-risk disease according to the D’Amico classification. The dose of the brachytherapy boost was escalated from 25 to 35Gy – 33pts. received 25Gy (total dose 75Gy), 63pts. 30Gy (total dose 80Gy) and 34pts. 35Gy, (total dose 85Gy) given in one session (dose per pulse was 0.60Gy or 0.70Gy/h, 24h per day, night and day, with a time interval of 1h between two pulses). PSA-recurrence-free survival according to Kaplan–Meier using the Phoenix definition of biochemical failure was calculated and also late toxicities according to Common Toxicity Criteria scale were assessed. ResultsAt the time of analysis with a median follow-up of 60months biochemical control was achieved by 88% of patients – only 16/130 patients (12.3%) developed a biochemical relapse. Biochemical relapse free survival calculated according to Kaplan–Meier for all patients at 5years was 85.6% (83.9% for intermediate-risk patients and 84.2% for high-risk patients) and at 9years’ follow up it was 79.0%. Analysing biochemical relapse free survival separately for different boost dose levels, at 5years it was 97% for the 35Gy boost dose and 82% for the 25 and 30Gy dose levels. The side effects of therapy were negligible: There were 18 cases (15%) of grade 1/2 rectal proctitis, one case (0.8%) of grade 3 proctitis, 18 cases (15%) of grade 1/2 cystitis, and no cases (0%) with dysuria grade 3. No patient had a bulbourethral stricture requiring dilation or new onset incontinence. ConclusionsImage-guided conformal PDR-brachytherapy using up to 35Gy as boost dose after 50Gy of external beam radiation therapy (total dose up to 85Gy) is a very effective treatment option with very low morbidity in patients with intermediate or high risk prostate cancer. Further dose escalation seems possible.

Deriving Prostate Alpha-Beta Ratio Using Carefully Matched Groups, Long Follow-Up and the Phoenix Definition of Biochemical Failure

Prior studies have derived low values of alpha-beta ratio (a/ß) for prostate cancer of approximately 1-2 Gy. These studies used poorly matched groups, differing definitions of biochemical failure, and insufficient follow-up. National Comprehensive Cancer Network low- or low-intermediate risk prostate cancer patients, treated with external beam radiotherapy or permanent prostate brachytherapy, were matched for prostate-specific antigen, Gleason score, T-stage, percentage of positive cores, androgen deprivation therapy, and era, yielding 118 patient pairs. The Phoenix definition of biochemical failure was used. The best-fitting value for a/ß was found for up to 90-month follow-up using maximum likelihood analysis, and the 95% confidence interval using the profile likelihood method. Linear quadratic formalism was applied with the radiobiological parameters of relative biological effectiveness = 1.0, potential doubling time = 45 days, and repair half-time = 1 hour. Bootstrap analysis was performed to estimate uncertainties in outcomes, and hence in a/ß. Sensitivity analysis was performed by varying the values of the radiobiological parameters to extreme values. The value of a/ß best fitting the outcomes data was >30 Gy, with lower 95% confidence limit of 5.2 Gy. This was confirmed on bootstrap analysis. Varying parameters to extreme values still yielded best-fit a/ß of >30 Gy, although the lower 95% confidence interval limit was reduced to 0.6 Gy. Using carefully matched groups, long follow-up, the Phoenix definition of biochemical failure, and well-established statistical methods, the best estimate of a/ß for low and low-tier intermediate-risk prostate cancer is likely to be higher than that of normal tissues, although a low value cannot be excluded.

Evaluating the Phoenix Definition of Biochemical Failure After 125I Prostate Brachytherapy: Can PSA Kinetics Distinguish PSA Failures From PSA Bounces?

To evaluate the prostate-specific antigen (PSA) kinetics of PSA failure (PSAf) and PSA bounce (PSAb) after permanent (125)I prostate brachytherapy (PB). The study included 1,006 consecutive low and "low tier" intermediate-risk patients treated with (125)I PB, with a potential minimum follow-up of 4 years. Patients who met the Phoenix definition of biochemical failure (nadir + 2 ng/mL(-1)) were identified. If the PSA subsequently fell to ≤0.5 ng/mL(-1)without intervention, this was considered a PSAb. All others were scored as true PSAf. Patient, tumor and dosimetric characteristics were compared between groups using the chi-square test and analysis of variance to evaluate factors associated with PSAf or PSAb. Median follow-up was 54 months. Of the 1,006 men, 57 patients triggered the Phoenix definition of PSA failure, 32 (56%) were true PSAf, and 25 PSAb (44%). The median time to trigger nadir + 2 was 20.6 months (range, 6-36) vs. 49 mo (range, 12-83) for PSAb vs. PSAf groups (p < 0.001). The PSAb patients were significantly younger (p < 0.0001), had shorter time to reach the nadir (median 6 vs. 11.5 months, p = 0.001) and had a shorter PSA doubling time (p = 0.05). Men younger than age 70 who trigger nadir +2 PSA failure within 38 months of implant have an 80% likelihood of having PSAb and 20% chance of PSAf. With adequate follow-up, 44% of PSA failures by the Phoenix definition in our cohort were found to be benign PSA bounces. Our study reinforces the need for adequate follow-up when reporting PB PSA outcomes, to ensure accurate estimates of treatment efficacy and to avoid unnecessary secondary interventions.

Commentary on High-intensity focused ultrasound for prostate cancer: Comparative definitions of biochemical failure: Blana A, Brown SC, Chaussy C, Conti GN, Eastham JA, Ganzer R, Murat FJ, Pasticier G, Rebillard X, Rewcastle JC, Robertson CN, Thuroff S, Ward JF, Harlaching Hospital, Munich, Germany

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. Consecutively treated patients who underwent HIFU between October 1997 and July 2006 at two centers (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. The data from 285 patients (stage ≤ T2, PSA < 15 ng/mL, Gleason score ≤ 7) were analyzed. 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 1.1–1.3 ng/mL, PSA velocities of <0.3 ng/mL/y, and PSA doubling times of 1.25–1.75 years. 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.”

High‐intensity focused ultrasound for prostate cancer: comparative definitions of biochemical failure

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. 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. The data from 285 patients (stage <or= T2, PSA <15 ng/mL, Gleason score <or=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. 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'.

7026 Deriving prostate alpha-beta ratio using carefully matched groups, long follow-up and the Phoenix definition of biochemical failure

Since appropriate and timetable methods in trauma care have an important impact on patients’ outcome we evaluated the effect of Advanced Trauma Life Support (ATLS) program on medical interns’ performance in simulated trauma patient managementA descriptive and analytical study before and after the training was conducted on 24 randomly selected undergraduate medical interns from Imam Reza Hospital in Mashhad, Iran. On the first day, we assessed interns’ clinical knowledge and their practical skill performance in confronting simulated trauma patients. After 2 days of ATLS training, we performed the same study and evaluated their score again on the fourth day. The two findings, preand post- ATLS periods, were compared through SPSS version 15.0 software. P values less than 0.05 were considered statistically significant.Our findings showed that interns’ ability in all the three tasks improved after the training course. On the fourth day after training, there was a statistically significant increase in interns’ clinical knowledge of ATLS procedures, the sequence of procedures and skill performance in trauma situations (P < 0.001, P = 0.016 and P = 0.01 respectively).ATLS course has an important role in increasing clinical knowledge and practical skill performance of trauma care in medical interns.

2035 Radiobiological modelling of hypofractionated accelerated partial breast irradiation (APBI) with 50 kV x rays from a miniature isotropic source

We reviewed our seven year single institution experience with pulsed dose rate brachytherapy dose escalation study in patients with intermediate and high risk prostate cancer.We treated a total of 130 patients for intermediate and high risk prostate cancer at our institution between 2000 and 2007 using PDR-brachytherapy as a boost after conformal external beam radiation therapy to 50.4 Gy. The majority of patients had T2 disease (T1c 6%, T2 75%, T3 19%). Seventy three patients had intermediate-risk and 53 patients had high-risk disease according to the D’Amico classification. The dose of the brachytherapy boost was escalated from 25 to 35 Gy – 33 pts. received 25 Gy (total dose 75 Gy), 63 pts. 30 Gy (total dose 80 Gy) and 34 pts. 35 Gy, (total dose 85 Gy) given in one session (dose per pulse was 0.60 Gy or 0.70 Gy/h, 24 h per day, night and day, with a time interval of 1 h between two pulses). PSA-recurrence-free survival according to Kaplan–Meier using the Phoenix definition of biochemical failure was calculated and also late toxicities according to Common Toxicity Criteria scale were assessed.At the time of analysis with a median follow-up of 60 months biochemical control was achieved by 88% of patients – only 16/130 patients (12.3%) developed a biochemical relapse. Biochemical relapse free survival calculated according to Kaplan–Meier for all patients at 5 years was 85.6% (83.9% for intermediate-risk patients and 84.2% for high-risk patients) and at 9 years’ follow up it was 79.0%. Analysing biochemical relapse free survival separately for different boost dose levels, at 5 years it was 97% for the 35 Gy boost dose and 82% for the 25 and 30 Gy dose levels. The side effects of therapy were negligible: There were 18 cases (15%) of grade 1/2 rectal proctitis, one case (0.8%) of grade 3 proctitis, 18 cases (15%) of grade 1/2 cystitis, and no cases (0%) with dysuria grade 3. No patient had a bulbourethral stricture requiring dilation or new onset incontinence.Image-guided conformal PDR-brachytherapy using up to 35 Gy as boost dose after 50 Gy of external beam radiation therapy (total dose up to 85 Gy) is a very effective treatment option with very low morbidity in patients with intermediate or high risk prostate cancer. Further dose escalation seems possible.

High‐intensity focused ultrasound for localized prostate cancer: initial experience with a 2‐year follow‐up

To report on the short-term functional and oncological results, from one institution, of high-intensity focused ultrasound (HIFU) for treating localized prostate cancer. 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 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 > or = 0.5 ng/mL, or starting salvage therapy, or the presence of cancer on biopsy after treatment. 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. 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 brachytherapy for localized prostate adenocarcinoma post abdominoperineal resection of the rectum and pelvic irradiation: Technique and experience

Purpose Treatment options are limited for patients with localized prostate cancer and a prior history of abdominoperineal resection (APR) and pelvic irradiation. We have previously reported on the successful utility of high-dose-rate (HDR) brachytherapy salvage for prostate cancer failing definitive external beam radiation therapy (EBRT). In this report, we describe our technique and early experience with definitive HDR brachytherapy in patients post APR and pelvic EBRT. Patients and Methods Six men with newly diagnosed localized prostate cancer had a prior history of APR and pelvic EBRT. Sixteen to 18 HDR catheters were placed transperineally under transperineal ultrasound–guidance. The critical first two catheters were placed freehand posterior to the inferior rami on both sides of the bulbar urethra under cystoscopic visualization. A template was used for subsequent catheter placement. Using CT-based planning, 5 men received 36 Gy in six fractions as monotherapy. One patient initially treated with EBRT to 30 Gy, received 24 Gy in four fractions. Results Median age was 67.5 (56–74) years. At a median followup of 26 (14–60) months, all patients are alive and with no evidence of disease per the Phoenix definition of biochemical failure, with a median prostate-specific antigen nadir of 0.19 ng/mL. Three men have reported grade 2 late genitourinary toxicity. There has been no report of grade 3–5 toxicity. Conclusion Transperineal ultrasound–guided HDR brachytherapy using the above technique should be considered as definitive therapy for patients with localized prostate cancer and a prior history of APR and pelvic EBRT.

Asians with Localized Prostate Cancer Treated with 3-Dimensional Conformal Radiation Therapy and Adjuvant Hormonal Therapy: Comparing Phoenix and American Society of Therapeutic Radiology and Oncology (ASTRO) Definitions in an Asian Population

Conformal radiotherapy with adjuvant androgen suppression is used in our center to treat localized prostate cancer. We compare Phoenix as an alternative to American Society of Therapeutic Radiology and Oncology (ASTRO) for defining biochemical failure. Our primary aim was to assess the Phoenix and ASTRO definitions of biochemical failure in a population of mainly Asian men with early localized prostate cancer treated with conformal radiotherapy with and without androgen ablation. We retrospectively analyzed 141 patients who were treated for T1/T2 cancer of the prostate in our center from January 1997 to June 2002 with a mean duration of follow-up of 62 months. Outcomes were analyzed by using both Phoenix and ASTRO definitions of biochemical failure as well as clinical failure. The Phoenix definition of biochemical failure was superior as measured by sensitivity, specificity, positive and negative predictive values, accuracy, and a greater concordance with clinical outcome as measured by Kappa analysis. The ASTRO definition helped to standardize reporting of biochemical failures post-radiotherapy but inadequacies have been identified especially when adjuvant hormone therapy has been given. The Phoenix definition has been noted to be a more accurate and precise description of biochemical failure in international series, and we find this to be true in our Asian population as well.

First Analysis of the Long-Term Results with Transrectal HIFU in Patients with Localised Prostate Cancer

ObjectiveTo evaluate the long-term efficacy of high-intensity focused ultrasound (HIFU) therapy for patients with localised prostate cancer. Material and methodsPatients included in this multicentre analysis had T1–T2 NxM0 prostate cancer, a PSA<15ng/ml, and a Gleason score (GS) ≤ 7, and were treated with prototypes or first-generation Ablatherm™ HIFU devices between October 1997 and August 2001. The Phoenix definition of biochemical failure was used (PSA nadir+2). Treatment failure was defined as: biochemical failure or positive biopsy. ResultsA total of 140 patients with a mean (SD) age 69.1 yr (6.6) were included. Mean (SD) follow-up was 6.4 yr (1.1). Control prostate biopsies were negative in 86.4% of patients. Median PSA nadir of 0.16ng/ml (range, 0.0–9.1) was achieved at a mean (SD) of 4.9 mo (5.2). A PSA nadir ≤ 0.5ng/ml was recorded in 68.4% of patients. The actuarial biochemical failure–free survival rates (SR) at 5 and 7 yr were 77% and 69%, respectively. The actuarial disease–free SR at 5 and 7 yr were 66% and 59%, respectively. ConclusionsThis study demonstrates the effective long-term cancer control achieved with HIFU in patients with low- or intermediate-risk localised prostate cancer.

The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer

The American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (BF) incorporates backdating, resulting in an artificial flattening of Kaplan-Meier curves and overly favorable estimates when follow-up is short. The nadir + 2 ng/mL (Nadir + 2; Phoenix) definition reduces these artifacts. The objective of the current study was to compare ASTRO and Phoenix BF estimates as determinants of distant metastasis (DM), cause-specific mortality (CSM), and overall mortality (OM). A total of 1831 patients with T1-4N0M0 prostate cancer were treated with external beam radiotherapy (RT) using conventional or three-dimensional conformal methods to at least 60 grays (Gy). The median follow-up was 71 months and the median RT dose was 72 Gy (range, 60-79 Gy). Cox regression models incorporating BF as a time-dependent covariate were used for both univariate and multivariate analyses. Other covariates included in the analyses were T classification, Gleason score, neoadjuvant/adjuvant androgen deprivation, age, RT dose, and pretreatment prostate-specific antigen. BF was observed in 389 men (21%) using the Phoenix definition and 460 men (25%) using the ASTRO definition. DM was observed in 84 patients (5%), 48 patients (3%) patients died of prostate cancer, and 404 patients (22%) died of any cause. The Phoenix definition of BF was found to be a significant predictor of DM, CSM, and OM, after controlling for other significant covariates. The ASTRO definition was found to be associated with CSM and DM, but not OM. The Phoenix definition of BF is a more robust determinant of patient outcome compared with the ASTRO definition. The correlation with mortality, including OM, and the independence of this correlation from the use of neoadjuvant/adjuvant androgen deprivation, supports the use of Nadir + 2 in prostate cancer clinical trials of RT with or without androgen deprivation.

The Phoenix Definition of Biochemical Failure Correlates With Clinical Failure for Men Treated With Adjuvant and Salvage Post-Prostatectomy Radiation: Results of the Multi-institutional Pooled Analysis

The Phoenix Definition of Biochemical Failure Correlates With Clinical Failure for Men Treated With Adjuvant and Salvage Post-Prostatectomy Radiation: Results of the Multi-institutional Pooled Analysis