Definitions Of Biochemical Failure Research Articles

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.

Locally Recurrent Prostate Cancer After Initial Radiation Therapy: A Comparison of Salvage Radical Prostatectomy Versus Cryotherapy

We compared the treatment outcomes of salvage radical prostatectomy and salvage cryotherapy for patients with locally recurrent prostate cancer after initial radiation therapy. We retrospectively reviewed the medical records of patients who underwent salvage radical prostatectomy at the Mayo Clinic between 1990 and 1999, and those who underwent salvage cryotherapy at M. D. Anderson Cancer Center between 1992 and 1995. Eligibility criteria were prostate specific antigen less than 10 ng/ml, post-radiation therapy biopsy showing Gleason score 8 or less and prior radiation therapy alone without pre-salvage or post-salvage hormonal therapy. We assessed the rates of biochemical disease-free survival, disease specific survival and overall survival in each group. Biochemical failure was assessed using the 2 definitions of 1) prostate specific antigen greater than 0.4 ng/ml and 2) 2 increases above the nadir prostate specific antigen. Mean followup was 7.8 years for the salvage radical prostatectomy group and 5.5 years for the salvage cryotherapy group. Compared to salvage cryotherapy, salvage radical prostatectomy resulted in superior biochemical disease-free survival by both definitions of biochemical failure (prostate specific antigen greater than 0.4 ng/ml, salvage cryotherapy 21% vs salvage radical prostatectomy 61% at 5 years, p <0.001; 2 increases above nadir with salvage cryotherapy 42% vs salvage radical prostatectomy 66% at 5 years, p = 0.002) and in superior overall survival (at 5 years salvage cryotherapy 85% vs salvage radical prostatectomy 95%, p = 0.001). There was no significant difference in disease specific survival (at 5 years salvage cryotherapy 96% vs salvage radical prostatectomy 98%, p = 0.283). After adjusting for post-radiation therapy biopsy Gleason sum and pre-salvage treatment serum prostate specific antigen on multivariate analysis salvage radical prostatectomy remained superior to salvage cryotherapy for the end points of any increase in prostate specific antigen greater than 0.4 ng/ml (HR 0.24, p <0.0001), 2 increases in prostate specific antigen (HR 0.47, p = 0.02) and overall survival (HR 0.21, p = 0.01). Young, healthy patients with recurrent prostate cancer after radiation therapy should consider salvage radical prostatectomy as it offers superior biochemical disease-free survival and may potentially offer the best chance of cure.

Two-years biochemical failure-free survival following high intensity focused ultrasound (HIFU) for localized prostate cancer: Prospective single center study of 196 patients

5117 Background: HIFU is an emerging ablative modality for the treatment of localized prostate cancer with limited reports on oncological outcome. We prospectively analyzed our 2-year results. Methods: 253 consecutive patients (age: 64+8) were treated with a planed single session of HIFU using the Ablatherm integrated imaging model system between January 2006 and June 2008. Patients were followed (median: 12; range 3–24 months) with PSA measurement every 3 months. Patients who received prior radiation or hormonal therapy (n=25) and patient for whom at least 2 consecutive PSA measurements were not available (n = 32) were excluded, leaving a total of 196 patients for analysis. Mean pre-treatment PSA was 6.9+3.3. Biopsy Gleason scores at diagnosis (median 9 cores) were 5, 6, 3+4, 4+3 in 1, 91, 66 and 38 patients, respectively. Biochemical failure (BCF) is reported using the Stephenson (PSA &gt;0.4ng/ml and rising), Horwitz (2 consecutive increases of at least 0.5ng/ml) and Phoenix (nadir+2ng/ml) definitions. Results: 196 patients (age: 64+8) met the inclusion criteria for analysis. 75 had low and 121 had intermediate D'Amico's risk stratification disease. Mean and median absolute PSA nadir levels were 0.28+0.53 and 0.06 ng/ml respectively. It was achieved in median time of 3 months and remained unchanged in 70% of the patients throughout the follow-up. Overall 2 years BCF free rates were 70 % (62–78%), 86 % (81–91%) and 96% (91–99%) according to the Stephenson, Horwitz and Phoenix definitions, respectively; with no significant differences between risk groups. Predictors of BCF were absolute nadir [HR: 3.0 (2.3–3.8)] and pre-treatment PSA [HR: 1.1 (1.0–1.2)]. Conclusions: This is the only study to date that analyzed post HIFU BCF free rates according to post radical prostatectomy definition of BCF. BCF usually occur in the first year and plateau thereafter. Short term results by all BCF definitions are promising with similar results for patients with low and intermediate risk. Pre-HIFU PSA and post-HIFU PSA nadir levels are predictors for BCF. [Table: see text]

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.

Salvage Therapy for Radiorecurrent Prostate Cancer

Locally recurrent prostate cancer after radiation therapy, also known as radiorecurrent prostate cancer, has an unfavorable prognosis. Two-thirds of patients with radiorecurrent prostate cancer have an advanced pathological disease status by the time they undergo salvage therapy. Several salvage therapies for radiorecurrent prostate cancer are available. Salvage radical prostatectomy (SRP) and salvage cryoablation are the most feasible and effective therapies for radiorecurrent prostate cancer. Although SRP is technically more difficult and has a higher complication rate than do other salvage therapies, the procedure provides a long-term survival benefit. Preliminary studies of salvage robot-assisted radical prostatectomy (SRARP) suggest that SRARP may be similar to or at least as effective as SRP. The intermediate oncological efficacy and morbidity of salvage cryoablation are similar to those of SRP. Prognostic factors for successful salvage therapy include serum prostate-specific antigen level ≤10 ng/mL, Gleason score ≤8, and a clinical disease stage T1c or T2. Assessing the comparative oncological efficacy and complications of the available salvage therapies for radiorecurrent prostate cancer requires strict guidelines, including universal patient selection criteria and an intergrade definition of biochemical failure.

Stereotactic Body Radiotherapy for Localized Prostate Cancer: Interim Results of a Prospective Phase II Clinical Trial

The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate cancer. Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed. The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir </=0.4 ng/mL. A PSA decline to progressively lower nadirs up to 3 years after treatment was observed. The early and late toxicity profile and PSA response for prostate SBRT are highly encouraging. Continued accrual and follow-up will be necessary to confirm durable biochemical control rates and low toxicity profiles.

No Effect of Statins on Biochemical Outcomes After Radiotherapy for Localized Prostate Cancer

To examine the effect of concurrent statin use during definitive radiotherapy (RT) on the biochemical outcomes for localized prostate cancer. A total of 968 patients treated with RT had information about medication use available. Of these, 23% had been taking using statins during RT. Progression-free survival (PFS) was determined by a biochemical failure definition of prostate-specific antigen nadir plus 2 ng/mL, clinical failure, start of androgen deprivation therapy, or death. The mean patient age was 68 years. The median radiation dose was 76 Gy. Of the patients, 29% underwent androgen deprivation therapy. The 5-year overall survival rate was 83%. The median PFS time was 7.8 years versus 6.4 years, and the 5-year PFS rate was 70% versus 59% in favor of the statin users (P = 0.03). The analysis by risk group demonstrated no significant statin effect in any of the three risk strata. Stratification by hydrophilic versus hydrophobic statin agents revealed similar results. Multivariate analysis revealed that T stage (P <0.0001), pretreatment prostate-specific antigen level (P <0.0001), and Gleason score (P = 0.0026) were significant predictors of PFS; however, statin use (P = 0.48), androgen deprivation therapy (P = 0.95), pelvic RT (P = 0.96), radiation dose (P = 0.13), age (P = 0.19), and year of treatment (P = 0.07) were not. Statin use did not affect PFS after adjusting for differences in treatment year and multiple prognostic factors. However, T stage, baseline prostate-specific antigen level, and Gleason score were critical determinants of prostate-specific antigen failure. These results did not differ when hydrophilic pravastatin was excluded.

PSA Doubling Time Predicts for the Development of Distant Metastases for Patients Who Fail 3DCRT or IMRT using the Phoenix Definition

PSA doubling time (PSADT) is commonly used as an indication for salvage androgen deprivation therapy (ADT) for PSA failure following RT. Previously, we have shown that PSADT of <12 months is an important predictor for the development of distant metastasis following 3DCRT using the former ASTRO definition of biochemical failure. The Phoenix definition (nadir+2) is a more robust definition of PSA failure following RT. We sought to determine if this definition to determine if this approach is still valid with IMRT in a larger dataset with longer follow-up.

Update of Dutch Multicenter Dose-Escalation Trial of Radiotherapy for Localized Prostate Cancer

To update the analysis of the Dutch dose-escalation trial of radiotherapy for prostate cancer. A total of 669 patients with localized prostate cancer were randomly assigned to receive 68 or 78 Gy. The patients were stratified by age, institution, use of neoadjuvant or adjuvant hormonal therapy, and treatment group. The primary endpoint was freedom from failure (FFF), with failure defined as clinical or biochemical failure. Two definitions of biochemical failure were used: the American Society for Therapeutic Radiology and Oncology definition (three consecutive increases in prostate-specific antigen level) and the Phoenix definition (nadir plus 2 microe secondary endpoints were freedom from clinical failure, overall survival, and genitourinary and gastrointestinal toxicity. After a median follow-up of 70 months, the FFF using the American Society for Therapeutic Radiology and Oncology definition was significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 54% vs. 47%, respectively; p = 0.04). The FFF using the Phoenix definition was also significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 56% vs. 45%, respectively; p = 0.03). However, no differences in freedom from clinical failure or overall survival were observed. The incidence of late Grade 2 or greater genitourinary toxicity was similar in both arms (40% and 41% at 7 years; p = 0.6). However, the cumulative incidence of late Grade 2 or greater gastrointestinal toxicity was increased in the 78-Gy arm compared with the 68-Gy arm (35% vs. 25% at 7 years; p = 0.04). The results of our study have shown a statistically significant improvement in FFF in prostate cancer patients treated with 78 Gy but with a greater rate of late gastrointestinal toxicity.

Editorial Comment on: Post-treatment Prostate Biopsies in the Era of Three-Dimensional Conformal Radiotherapy: What Can They Teach Us?

[9] D’Amico AV, Whittington R, Malkowicz SB, et al. A method for determining a prostate-specific antigen cure after radiation therapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 1995;32:473–7. [10] Vicini FA, Kestin LL, Martinez AA. The importance of adequate follow-up in defining treatment success after external beam irradiation for prostate cancer. Int J Radiat Oncol Biol Phys 1999;45:553–61. [11] Connell PP, Ignacio L, McBride RB, et al. Caution in interpreting biochemical control rates after treatment of prostate cancer: length of follow-up influences results. Urology 1999;54:875–9. [12] Kestin LL, Vicini FA, Martinez AA. Practical application of biochemical failure definitions: what to do and when to do it. Int J Radiat Oncol Biol Phys 2002;53:304–15. [13] Crook JM, Perry GA, Robertson S, et al. Routine prostate biopsies following adiotherapy for prostate cancer: results for 226 patients. Urology 1995;45:624–31. [14] Gaudin PB, Zelefsky MJ, Leibel SA, et al. Histopathologic effects of three-dimensional conformal external beam radiation therapy on benign and malignant prostate tissues. Am J Surg Pathol 1999;23:1021–31. [15] Prestidge BR, Hoak DC, Grimm PD, et al. Posttreatment biopsy results following interstitial brachytherapy in early stage prostate cancer. Int J Radiat Oncol Biol Phys 1997;37:31–9. [16] Crook JM, Bahadur YA, Robertson SJ, et al. Evaluation of radiation effect, tumor differentiation, and prostate specific antigen staining in sequential prostate biopsies after external beam radiotherapy for patients with prostate carcinoma. Cancer 1997;79:81–9.

State-of-the-art: prostate LDR brachytherapy

This article on low dose rate (LDR) prostate brachytherapy reviews long-term results, patient selection and quality of life issues. Mature results from the United States and United Kingdom are reported and issues regarding definitions of biochemical failure are discussed. Latest data comparing brachytherapy with radical prostatectomy or no definitive treatment and also the risk of secondary malignancies after prostate brachytherapy are presented. Urological parameters of patient selection and quality of life issues concerning urinary, sexual and bowel function are reviewed. The position of prostate brachytherapy next to surgery as a first-line treatment modality is demonstrated.

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.

Is It Possible to Compare PSA Recurrence-Free Survival After Surgery and Radiotherapy Using Revised ASTRO Criterion—“Nadir + 2”?

The new American Society for Therapeutic Radiology and Oncology/Radiation Therapy Oncology Group consensus definition of biochemical failure after radiotherapy for prostate cancer is defined as a prostate-specific antigen level at or greater than the absolute nadir PSA level plus 2 ng/mL. Because this definition inevitably will be used to compare cancer control rates after radiotherapy to those after surgery, this study examined the effect of this comparison. We reviewed the data from 2570 men who had undergone radical prostatectomy from 1985 to 2004. Biochemical failure was defined as any measurable PSA level of 0.2 ng/mL or greater. We evaluated how the nadir+2 definition affected the failure rate when applied to this series. The actuarial 5, 10, and 15-year biochemical recurrence-free survival probability with failure defined as a PSA level of 0.2 ng/mL or more and a PSA level of 2 ng/mL or more was 88.6%, 81.2%, and 78.1% and 94.6%, 89.4%, and 84.3%, respectively (P <0.0001). The median time to biochemical progression was 2.8 years for the greater than 0.2 ng/mL definition and 7.9 years for the 2 ng/mL or more definition. The nadir+2 definition systematically overestimated the biochemical recurrence-free survival, even after stratifying patients into standard prognostic risk groups, especially in men who developed local recurrence. When applied to a mature series of surgically treated patients with localized prostate cancer, the American Society for Therapeutic Radiology and Oncology "nadir+2" definition resulted in a systematic delay in the determination of biochemical failure. Because patients in this series who experienced a detectable PSA level took more than 5 years to progress to a PSA level of 2 ng/mL or greater, the 5-year biochemical control rates with the definition of 0.2 ng/mL or more should be compared with the 10-year biochemical control rates using the nadir+2 definition.

Radiothérapie conformationnelle à 76 Gy des cancers localisés de la prostate. Modalités thérapeutiques et résultats préliminaires

Purpose To describe therapeutic modalities for localized prostate cancer treated by conformal radiation to 76 Gy with or without androgen ablation. To evaluate the preliminary results in terms of survival, biological control and toxicity. Patients and method Between January 1998 and June 2001, 321 patients with localized prostate cancer were irradiated at institut Curie. Tumors were stratified into the three Memorial Sloan-Kettering Cancer Center prognostic groups (1998) for analysis: favorable risk group (FG) 23%, intermediate risk group (IG) 36.5%, unfavorable risk group (UG) 40.5%. Androgen deprivation, mainly neoadjuvant, less or equal to one year was prescribed to 93.8% of patients (72.6% less or equal to six months). Planning target volume prescription doses were: prostate: 76 Gy, seminal vesicles: 56 to 76 Gy, and pelvic lymph nodes: 44 Gy to 16.8% of patients. Results The five-year actuarial overall survival was 94% (95% IC: 90–97%). The median post-therapeutic follow-up was 36 months (nine to 60 months). The 48-month actuarial rates of biochemical control for the three prognostic groups were statistically different according to both the American Society for Therapeutic Radiology and Oncology consensus (ASTRO 1997) and the Fox Chase Cancer Center definitions of biochemical failure (FCCC 2000) with respectively 87 and 94% for FG, 78 and 84% for IG, 54 and 58% for UG ( P < 10 −6 and P < 10 −8). At time of our analysis, late post-treatment rectal and bladder bleedings were 17,4 and 13,6%, respectively. According to a 1–4 scale adapted from M.D. Anderson Cancer Center criteria: rectal bleedings were grade 1 (9.6%), grade 2 (6.2%) and grade 3 (1.6%). Bladder bleedings were grade 2 (13%) and grade 3 (0.6%). Analysis of rectal bleeding risk factors showed significant correlations with pelvic lymph nodes irradiation for grade 2 and 3, ( P = 0.02), and for all grades, a correlation with smaller rectal wall volumes ( P = 0.03), and greater percentages of rectal wall irradiated to higher doses: 65, 70, 72 and 75 Gy ( P = 0.02, P = 0.01, P = 0.0007 and P = 0.003, respectively). Conclusions These results are comparable to those previously reported with the same follow-up. Impact of dose escalation with short androgen deprivation on local control, survival and complications needs longer follow-up and further analysis.

Combined Permanent Implant and External-Beam Radiation Therapy for Prostate Cancer

A number of series have been published examining the utility of combining low-dose rate permanent interstitial implants with external-beam radiation (CMT). However, the data show conflicting results. Comparisons of these studies are confounded by the lack of similar biochemical failure definitions, inequities in risk groups between compared arms, variable implant quality, and differences in implant margins and techniques. Despite these limitations, the literature does suggest that CMT may help spare patients the need for androgen deprivation, overcome adverse pathologic factors, and correct for poor implant quality. We present the recent innovation and potential benefits of using implant dose-adjusted intensity-modulated radiation therapy.

Single Center Experience with Third-Generation Cryosurgery for Management of Organ-Confined Prostate Cancer: Critical Evaluation of Short-Term Outcomes, Complications, and Patient Quality of Life

Technical refinements such as improved ultrasonographic localization and the routine use of urethral warmers and small-gauge needle delivery systems have renewed interest in cryosurgical treatment as a minimally invasive option for selected patients with localized prostate cancer. Only three reports of quality of life (QoL) in prostate cryoablation exist, and none report on patients treated with third-generation cryoablative technology. We critically examine our initial series of consecutive patients at a single institution undergoing primary third-generation cryosurgical treatment of localized prostate cancer with respect to treatment outcome, morbidity profile, and QoL parameters. To our knowledge, this is the first QoL report on third-generation cryoablation of the prostate. We retrospectively review the records of 89 consecutive patients with median followup of 11 months (1-32) who have undergone third-generation cryosurgical ablation of the prostate as primary treatment for localized prostate cancer with intention to cure. Patients were risk stratified according to preprocedural parameters of prostate-specific antigen (PSA), clinical stage, and Gleason score. PSA trends were recorded and treatment effectiveness was observed using different definitions of biochemical failure. Charts were reviewed for postprocedure complications. Quality of life was measured prospectively using the University of California, Los Angeles, Prostate Cancer Index as well as American Urological Association symptom scores. We compare a percent of baseline score (%BS) for various domains between our series of patients treated with primary cryoablation with a series of patients undergoing brachytherapy for localized prostate cancer. Treatment success was defined by achievement of a PSA nadir of < or =0.1 ng/mL and by biochemical disease-free survival (BDFS) assessed with both a PSA threshold of < or =0.4 ng/dL over time and the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of three consecutive rises in PSA. According to risk stratification, 86%, 81.5%, and 78% of low-, intermediate-, and high-risk patients, respectively, achieved a PSA nadir of < or =0.1 ng/mL. Overall, at 12 months follow-up, 94% of patients achieved BDFS using ASTRO criteria while 70% achieved BDFS using a PSA threshold of < or =0.4 ng/mL. With risk stratification, 74%, 70%, and 60% of low-, intermediate-, and high-risk patients, respectively, achieved BDFS defined by PSA threshold of < or =0.4 ng/mL. Complications were rare. The response rate for Health Related Quality of Life (HRQoL) questionnaires was 71% for cryoablation patients and 51% for brachytherapy patients. At 12 months follow-up, patients undergoing cryoablation on average achieved urinary and bowel domain scores comparable to baseline, but sexual domains remained well below baseline. When compared with a brachytherapy series with better baseline sexual function (P = 0.04) and urinary function (P = 0.03), cryotherapy patients experienced more negative impact on sexual function steadily for up to 12 months (P = 0.02). Urinary function was similar between the groups until 18 months, at which time cryoablation patients fared better (P = 0.01); this was sustained up to 24 months (P = 0.04). Treatment success with cryosurgery varies with definition; however, our results are comparable to other series with regard to short-term cancer control. Complication rates in this series of third-generation cryosurgical patients are low. QoL characteristics of third-generation cryoablation are similar to those described in second-generation cryoablation series. Compared with brachytherapy, cryotherapy results in less irritative and obstructive voiding symptoms in the early post-treatment period and may improve urinary function up to 24 months after treatment. In a small group of older patients with baseline erectile dysfunction undergoing cryoablation, sexual function returns to 20% of its baseline value with up to 12 months follow-up.

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.