Biochemical Failure-free Rate Research Articles

The prognostic significance of additional localized treatment to primary lesion in patients undergoing hormone therapy for metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis.

We aimed to compare the prognostic values of 'localized treatment to the primary lesion (LT) plus hormone therapy (HT)' versus 'HT alone' in metastatic hormone-sensitive prostate cancer (mHSPC). We conducted a systematic search through the databases of PubMed®, Web of Science®, and Cochrane library® in April 2023 based on the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) statement. A pooled meta-analysis was performed to assess the prognostic differences between LT + HT and HT alone according to randomized and non-randomized controlled studies (RCTs and NRCTs, respectively). The search identified three RCTs and eight NRCTs. In RCTs, LT did not show prognostic benefits regarding biochemical-failure free rate nor overall survival (OS), although in patients with low tumor burdens, the LT + HT group showed better OS (HR: 0.68, 95% CI: 0.54-0.86). In the NRCTs, the LT+HT group showed superior progression-free survival (hazard ratio (HR): 0.42, 95% confidence interval (CI): 0.21-0.87), cancer-specific survival (HR: 0.39, 95% CI: 0.20-0.76), and OS (HR: 0.63, 95% CI: 0.57-0.69) to the HT alone group. In addition, better OS was observed in the LT +HT group regardless of the type of treatment modality for LT; radical prostatectomy (HR: 0.52, 95% CI: 0.39-0.69), radiotherapy (HR: 0.63, 95% CI: 0.56-0.71) in NRCTs. LT to the primary lesion in metastatic hormone-sensitive prostate cancer may provide prognostic benefits and especially in patients with low tumor burden.

Impact of prostate position-based image-guidance in intensity-modulated radiation therapy for localized prostate cancer.

The long-term clinical impact of prostate position-based image-guided radiotherapy (IGRT) for localized prostate cancer remains unclear. We retrospectively compared clinical outcomes following intensity-modulated radiation therapy (IMRT) with cone-beam computed tomography-based prostate position-based IGRT (P-IGRT) or without P-IGRT (non-P-IGRT). From June 2011, we applied P-IGRT in IMRT for intermediate-risk (IR) prostate cancer (PCa) (D'Amico risk classification) (76Gy in 38 fractions, with smaller margins). Clinical outcomes of patients who received P-IGRT between June 2011 and June 2019 were retrospectively compared with those of patients with IR PCa who received IMRT without P-IGRT between October 2002 and May 2011 in our institution (74Gy in 37 fractions). A total of 222 consecutive patients were analyzed: 114 in the P-IGRT cohort and 108 in the non-P-IGRT cohort. The median follow-up period after IMRT was 7.1years for the P-IGRT cohort and 10.8years for the non-P-IGRT cohort. The biochemical failure-free rate was significantly better in the P-IGRT cohort (94.9% for the P-IGRT cohort vs 82.7% for the non-P-IGRT cohort at 10years, p = 0.041). The rate of rectal bleeding which needs intervention including the use of suppositories was significantly lower in the P-IGRT cohort (p < 0.001). The use of P-IGRT with higher doses and smaller margins was correlated with significantly better biochemical control, and a lower incidence of rectal bleeding in IMRT for intermediate-risk prostate cancer. The enhanced accuracy using P-IGRT has the potential to independently improve disease control and reduce late rectal bleeding.

Impact of Long-term Adjuvant Hormonal Therapy in High-dose IMRT for Unfavorable Locally Advanced Prostate Cancer.

The aim of this study was to evaluate the benefit of adding long-term adjuvant hormonal therapy to high-dose intensity-modulated radiation therapy for locally advanced prostate cancer patients with multiple unfavorable risks. All cT3-4N0M0 prostate cancer patients with Gleason score 8-10 and prostate-specific antigen ≥30 ng/ml who received intensity-modulated radiation therapy to the prostate and seminal vesicle alone (78 Gy in 39 fractions) between September 2000 and June 2017 at our institution were analyzed retrospectively. All patients received short-term neoadjuvant hormonal therapy. Before May 2011, salvage hormonal therapy was initiated when prostate-specific antigen levels exceeded 4.0 ng/ml (early salvage hormonal therapy cohort). In June 2011, 2-year adjuvant hormonal therapy was added (adjuvant hormonal therapy cohort). Clinical outcomes were retrospectively compared using the log-rank test. In total, 88 patients (44 in both cohorts) were analyzed. Median follow-up periods were 10.9 and 6.1 years in early salvage hormonal therapy and adjuvant hormonal therapy cohorts, respectively. No significant difference in overall survival rates was observed (p=0.58). Disease controls were significantly better in the adjuvant hormonal therapy cohort: 95.5 versus 73.6% for castration-resistant prostate cancer-free rate (p=0.04), and 73.6 versus 34.1% for biochemical failure-free rate (p<0.001), both at 8 years, respectively. Among locally advanced prostate cancer patients with multiple unfavorable risks, adding long-term adjuvant hormonal therapy to high-dose intensity-modulated radiation therapy resulted in significantly better disease control than short-term hormonal therapy, even when salvaged early after biochemical failure.

A Prospective Study of Magnetic Resonance Imaging-guided Focal Salvage High-dose-Rate Brachytherapy for Radiorecurrent Prostate Cancer: Updated Results of 30 Patients

PurposeLimited prospective data on focal salvage high-dose-rate (HDR) prostate brachytherapy is available. We sought to explore the toxicities, health-related quality of life (HRQoL), and efficacy of focal salvage HDR brachytherapy in a prospective clinical trial. This report presents the updated results of previously published data. Methods and MaterialsPatients with locally recurrent prostate cancer after previous external beam radiation therapy and/or brachytherapy were enrolled. Patients received magnetic resonance imaging (MRI)-guided, ultrasound-based focal HDR brachytherapy delivered over 2 fractions of 13.5 Gy delivered 1 to 2 weeks apart. Androgen deprivation therapy (ADT) was not used. ResultsThirty patients were treated between 2012 and 2019. At a median follow-up time of 39 months, the 3-year biochemical failure-free rate was 61.8% (95% confidence interval, 44.0%-86.6%), and the 3-year ADT/salvage therapy-free rate was 86.0% (95% confidence interval, 74.1%-99.8%). Seventeen patients experienced subsequent biochemical failure, 9 received ADT and/or further local salvage, and no patients died of prostate cancer. Of the 28 patients who had posttreatment MRI, 26 had a local treatment response. No acute grade ≥3 genitourinary/gastrointestinal toxicity was observed. One temporary late grade 3 genitourinary toxicity event occurred, but no late grade ≥3 gastrointestinal toxicity was seen. No significant decline in urinary or bowel HRQoL was observed. ConclusionsFocal salvage HDR brachytherapy has a favorable side effect profile, no significant decline in HRQoL, and the 3-year biochemical control rates are in line with those of other salvage options. Early MRI response at the treated site is common, but does not preclude subsequent biochemical failure.

Radiation Therapy for Recurrent or Residual Pituitary Macroadenoma Invading Extrasellar Structures.

This study aimed to evaluate the efficacy of radiation therapy (RT) for recurrent or residual pituitary macroadenoma (PMA) invading extrasellar regions. Patients from 2000 to 2020 who received RT with conventional fractionation for recurrent or residual PMA were included. The patients were divided according to the type of tumor [functioning (fx) or non-fx] and the aim of RT (salvage RT alone, immediate postoperative RT, delayed postoperative RT). Local and biochemical failure-free rates (FFR) were calculated using the Kaplan-Meier method. With a median follow up of 82 months (IQR; 42-132 months), 36 patients treated with conventional RT (total 45-54 Gy in 1.8 or 2 Gy per fraction) for recurrent or residual PMA were analyzed. The 10-year local FFRs after RT for non-fx and fx tumor were 100% and 74.4%, respectively (p=0.047). In the immediate postoperative RT group, the 10-year local FFR was 100%, which was higher than the 90% FFR for salvage RT alone or 80% FFR for the delayed postoperative RT group (overall p=0.043, immediate vs. salvage; p=0.312, immediate vs. delayed; p=0.072). The local FFR was compared according to size of tumor with a cut-off value of 4 cm, and there was no significant difference (10-year local FFR 100% vs. 84.7% for >4 cm vs. <4 cm, p=0.320). The extents of extrasellar region invasion were not predictive of local failure after RT. We found no grade ≥3 acute toxicities or newly developed visual impairments as a late toxicity of RT. Conventional RT is safe and effective for the local control of recurrent or residual PMA. Our data suggest that immediate postoperative RT can be beneficial in recurrent or residual PMA, although further studies to evaluate risk factors of treatment failure in terms of treatment and disease characteristics are required.

Effect of adding androgen deprivation therapy to permanent iodine-125 implantation with or without external beam radiation therapy on the outcomes in patients with intermediate-risk prostate cancer: A propensity score–matched analysis

PurposeThe purpose of the study was to evaluate the effect of adding androgen deprivation therapy (ADT) to brachytherapy with or without external beam radiation therapy on oncological outcomes in prostate cancer. Methods and MaterialsOverall, 1,171 patients with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy with or without ADT between 2003 and 2013 were identified. Propensity score matching was used to counter biases between the ADT and non-ADT groups. The biochemical failure-free rate (bFFR), local recurrence-free rate, and overall survival rate were evaluated using Kaplan–Meier curves, and predictors were identified using Cox proportional hazards regression models. ResultsAfter propensity score matching, 405 patients were included in each group. The median followup duration was 9.1 years; the median ADT duration was 6 months. In the ADT versus non-ADT groups, the 9-year bFFR, local recurrence-free rate, and overall survival rate were 93.4% versus 87.8% (p = 0.016), 96.9% versus 98.1% (p = 0.481), and 88.1% versus 90.4% (p = 0.969), respectively. On multivariate analyses, Gleason score (hazard ratio [HR]: 2.52, 95% confidence interval [CI]: 1.58–4.03) and ADT use (HR: 0.55, 95% CI: 0.34–0.89) were associated with biochemical failure. Supplemental external beam radiation therapy use (HR: 0.38, 95% CI: 0.16–0.91) was associated with lower local recurrence rates. Age (HR: 1.12, 95% CI: 1.08–1.16) and comorbidities (HR: 1.56, 95% CI: 1.04–2.34) were associated with all-cause mortality. ConclusionsA risk-benefit assessment between bFFR improvement and the potential side effects of adding ADT to brachytherapy-based radiotherapy is warranted before incorporating ADT as routine practice.

Intensity-modulated radiation therapy for elderly patients (aged ≥75 years) with localized prostate cancer: Comparison with younger patients (aged

The aim of the present study was to evaluate the efficacy and safety of intensity-modulated radiation therapy (IMRT) for elderly patients with prostate cancer (age ≥75 years) compared with younger patients (<75 years). The numbers of patients enrolled into the elderly and younger groups were 238 and 853, respectively. More than half of the patients in the elderly group were high-risk, and the total risk of the elderly group was higher than that of younger group. The median follow-up periods for the elderly and younger groups were 42 (range, 2-108) and 49 (range, 2-120) months, respectively. All patients were treated with IMRT at a dose of 74-78 Gy with or without androgen-deprivation therapy. The biochemical failure-free rates (BFFRs) at 3-year follow-up for the elderly and younger groups were 93.3 and 95.7%, respectively; there was no significant difference between the 2 groups in regard to the BFFR. The clinical failure-free rates (CFFR) at 3-year follow-up for the elderly and younger groups was 95.8 and 98.5%, respectively; the 2 groups did not differ significantly in regard to the CFFR. The cumulative incidence rates of gastrointestinal toxicity (grade ≥2) and genitourinary toxicity (grade ≥2) at 3-year follow-up were 10.5 and 1.3%, respectively; there was no significant difference between the elderly and younger groups. It was concluded that in prostate cancer patients aged 75 years or older, IMRT has a treatment effect equivalent to that in patients <75 years old; adverse events are also comparable.

Image-guided stereotactic body radiation therapy for localized prostate cancer

We report the results of a retrospective study of stereotactic body radiation therapy (SBRT) using CyberKnife for localized prostate cancer. The study focused on the safety and feasibility of this treatment modality. Between October 2002 and December 2007, 44 patients suffering from localized adenocarcinoma of the prostate were treated with SBRT using CyberKnife at the Korea Cancer Center Hospital. The patients were divided into 3 groups: a low-risk group (5 patients), an intermediate-risk group (10 patients), and a high-risk group (29 patients). Five patients received 32 Gy in 4 fractions, 28 patients received 34 Gy in 4 fractions, and 11 patients received 36 Gy in 4 fractions. The median age of the patients was 69 years (range, 53-79 years) and the median duration of follow-up 40 months (range, 12-78 months). There were 6 acute and 3 late grade 2 urinary toxicities, and 4 acute and 5 late grade 2 rectal toxicities, but there were no grade 3 or higher treatment-related toxicities. The 5-year cause-specific survival rate and progression-free survival rate were both 100%. At last follow-up, the biochemical failure-free rate of the low-risk, intermediate-risk and high-risk patients was 100%, 100% and 90.8%, respectively. SBRT using CyberKnife for localized prostate cancer is safe and well tolerated. We obtained promising results with 34 Gy in a 4-fraction regimen especially for the high-risk patients.

Treatment outcomes and late toxicities of intensity-modulated radiation therapy for 1091 Japanese patients with localized prostate cancer.

This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer. A total of 1091 patients with localized prostate cancer were recruited between March 2006 and July 2014. The patients were stratified into low- (n=205 [18.8%]), intermediate- (n=450 [41.2%]), high- (n=345 [31.6%]), and very high-risk (n=91 [8.3%]) groups according to the National Comprehensive Cancer Network classification. All patients were irradiated via IMRT at a dose of 74-78Gy with or without androgen-deprivation therapy. The mean follow-up period was 50 months (range, 2-120 months). The biochemical failure-free rate (BFFR), the clinical failure-free rate, and the overall survival rate at the 5-year follow-up for all patients was 91.3%, 96.2%, and 99.1%, respectively. In univariate analysis, the prostate-specific antigen (PSA) levels (≤20 vs. >20ng/ml) were significantly correlated with BFFR. A trend toward higher BFFR was noted in patients with a Gleason score (GS) of ≤7 than in patients with GS ≥8. In multivariate analysis, only PSA (≤20 vs. >20ng/ml) was significantly correlated with BFFR. The cumulative incidence rate of gastrointestinal and genitourinary toxicity (≥grade 2) at the 5-year follow-up was 11.4% and 4.3%, respectively. The findings of this study indicate that IMRT is well tolerated and is associated with both good long-term tumor control and excellent outcomes in patients with localized prostate cancer.

Usefulness of ultra-sensitive prostate-specific antigen following radical prostatectomy.

This study aimed to evaluate the usefulness of ultra-sensitive prostate-specific antigen (PSA) following radical prostatectomy (RP). Between September, 2003 and March, 2009, a total of 311 prostate cancer patients underwent antegrade RP; following the exclusion of 111 patients due to prior hormonal therapy, 200 patients were finally included in this study. The results of the multivariate analysis identified RP Gleason score, extraprostatic extension, lymph node metastasis and PSA nadir as significant predictors of biochemical failure (P=0.0116, 0.0216, 0.0178 and <0.0001, respectively) and PSA nadir <0.008 ng/ml exhibited the highest hazard ratio (HR) [HR=26.34; 95% confidence interval (CI): 7.34-104.69]. After a median follow-up period of 52.2 months, the biochemical failure-free rate in the PSA nadir <0.008 and ≥0.008 ng/ml groups was 94.3 and 58.8%, respectively, with a statistically significant difference according to the log-rank test (P<0.001). In the multivariate analysis, statistically significant differences were observed only in pathological nodel stage within the PSA nadir <0.008 ng/ml group (P=0.0107). For this reason, postoperative follow-up using ultra-sensitive PSA is considered to be of value, since the use of high-sensitivity PSA to confirm a reduction to below postoperative measurement threshold value (PSA nadir <0.008 ng/ml) may avert administering unnecessary additional treatment, regardless of pathological reccurrence factors.

Toxicity and efficacy of three dose-fractionation regimens of intensity-modulated radiation therapy for localized prostate cancer

Outcomes of three protocols of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. A total of 259 patients treated with 5-field IMRT between 2005 and 2011 were analyzed. First, 74 patients were treated with a daily fraction of 2.0 Gy to a total of 74 Gy (low risk) or 78 Gy (intermediate or high risk). Then, 101 patients were treated with a 2.1-Gy daily fraction to 73.5 or 77.7 Gy. More recently, 84 patients were treated with a 2.2-Gy fraction to 72.6 or 74.8 Gy. The median patient age was 70 years (range, 54–82) and the follow-up period for living patients was 47 months (range, 18–97). Androgen deprivation therapy was given according to patient risk. The overall and biochemical failure-free survival rates were, respectively, 96 and 82% at 6 years in the 2.0-Gy group, 99 and 96% at 4 years in the 2.1-Gy group, and 99 and 96% at 2 years in the 2.2-Gy group. The biochemical failure-free rate for high-risk patients in all groups was 89% at 4 years. Incidences of Grade ≥2 acute genitourinary toxicities were 9.5% in the 2.0-Gy group, 18% in the 2.1-Gy group, and 15% in the 2.2-Gy group (P = 0.29). Cumulative incidences of Grade ≥2 late gastrointestinal toxicity were 13% in the 2.0-Gy group at 6 years, 12% in the 2.1-Gy group at 4 years, and 3.7% in the 2.2-Gy group at 2 years (P = 0.23). So far, this stepwise shortening of treatment periods seems to be successful.

What is optimal timing of post prostatectomy radiotherapy? Is adjuvant radiotherapy equivalent to early salvage radiotherapy? The “RAVES” phase III randomized clinical trial.

TPS4690 Background: Three randomised trials have demonstrated a significant benefit of adjuvant post prostatectomy radiotherapy in patients with positive margins, extra capsular extension or seminal vesicle involvement, and it should be regarded as current standard of care. However, adopting this approach will expose nearly half of such patients to unnecessary radiotherapy and potential treatment morbidity. Salvage radiotherapy, if given early, is recognised to be effective. The RAVES trial is designed to compare these two approaches, and was developed in collaboration with the Trans Tasman Radiation Oncology Group (TROG), Australian and New Zealand Urogenital and Prostate Trials Group (ANZUP) and the Urological Society of Australia and New Zealand (USANZ). It aims to test the hypothesis that active surveillance with early salvage radiotherapy is non-inferior to adjuvant radiotherapy with respect to risk of biochemical failure (defined as PSA level ≥ 0.40 ng/mL and rising). Methods: Patients must have at least one of the following risk factors: positive margins, extracapsular extension or seminal vesicle involvement. They must start radiotherapy within 4 months of radical prostatectomy (RP) and have an undetectable PSA (≤ 0.10 ng/ml) prior to randomisation. Patients receiving androgen deprivation or who have an artificial hip are excluded. Eligible patients are randomised to either: Arm 1: Adjuvant RT (64Gy in 32#) commenced within 4 months of RP, or Arm 2: Active surveillance with 3 monthly PSA tests and commencement of early salvage RT (64Gy in 32#) if PSA rises ≥ 0.20 ng/ml. Stratification is by seminal vesicle invasion, Gleason Score, pre-operative PSA, margin positivity (no/yes) and radiotherapy institution. A sample size of 470 patients is required to detect a 10% non-inferiority margin in the 5-year biochemical failure-free rate between the adjuvant and active surveillance arms. As of 31 Jan 2012, 186 patients have been recruited across 26 centres in Australia and New Zealand. A meta analysis with the MRC RADICALS and GETUG-17 trials will be prospectively designed to detect a survival difference between the two approaches.

Inverse Relationship Between Biochemical Outcome and Acute Toxicity After Image-Guided Radiotherapy for Prostate Cancer

Prostate cancer patients exhibit variability in normal tissue reactions and biochemical failure. With the use of image-guided radiotherapy (IGRT), there is a greater likelihood that the differences in normal tissue and tumor response are due to biological rather than physical factors. We tested the hypothesis that prospectively scored acute toxicity is associated with biochemical failure-free rate (BFFR) in prostate cancer patients treated with IGRT. We retrospectively analyzed BFFR in 362 patients with localized prostate cancer treated with IGRT. We compared BFFR with prospectively collected Radiation Therapy Oncology Group (RTOG) maximum acute gastrointestinal (GI) and genitourinary (GU) toxicity scores. Median follow-up for all patients was 58.3 months after total radiotherapy doses of 75.6-79.8 Gy. Patients reporting RTOG acute GU or GI toxicity scores of ≥ 2 were considered "sensitive" (n = 141, 39%) and patients reporting scores <2 were considered "nonsensitive" (n = 221, 61%). When calculating biochemical failure (BF) using the American Society for Therapeutic Radiology and Oncology definition at 5 years, 76% (CI 70-82%) of the "nonsensitive" patients were failure free, compared with only 53% (CI 43-62%) of the "sensitive" patients (log-rank test, p < 0.0001). This difference was also observed using the Phoenix definition; "nonsensitive" 5-year BFFR was 81% (CI 74-86%) vs. "sensitive" BFFR was 68% (CI 58-76%; log-rank test p = 0.0012). The difference in BF between cohorts remained significant when controlled for radiation dose (75.6 vs. 79.8 Gy), prognostic stratification (T category, prostate-specific antigen, and Gleason score), and prostate volume. This study unexpectedly shows that prostate cancer patients who develop ≥ Grade 2 RTOG acute toxicity during radiotherapy are less likely to remain BFF at 5 years. These results deserve further study and, if validated in other large IGRT cohorts, additional models would be required to study interaction between normal tissue and tumor biology in prostate cancer patients.

Image-Guided Stereotactic Body Radiation Therapy for Localized Prostate Cancer

We report the results of a retrospective study of stereotactic body radiation therapy (SBRT) using CyberKnife for localized prostate cancer. The study focused on the safety and feasibility of this treatment modality. Between October 2002 and December 2007, 44 patients suffering from localized adenocarcinoma of the prostate were treated with SBRT using CyberKnife at the Korea Cancer Center Hospital. The patients were divided into 3 groups: a low-risk group (5 patients), an intermediate-risk group (10 patients), and a high-risk group (29 patients). Five patients received 32 Gy in 4 fractions, 28 patients received 34 Gy in 4 fractions, and 11 patients received 36 Gy in 4 fractions. The median age of the patients was 69 years (range, 53-79 years) and the median duration of follow-up 40 months (range, 12-78 months). There were 6 acute and 3 late grade 2 urinary toxicities, and 4 acute and 5 late grade 2 rectal toxicities, but there were no grade 3 or higher treatment-related toxicities. The 5-year cause-specific survival rate and progression-free survival rate were both 100%. At last follow-up, the biochemical failure-free rate of the low-risk, intermediate-risk and high-risk patients was 100%, 100% and 90.8%, respectively. SBRT using CyberKnife for localized prostate cancer is safe and well tolerated. We obtained promising results with 34 Gy in a 4-fraction regimen especially for the high-risk patients.

Impact of Hormonal Therapy on Intermediate Risk Prostate Cancer Treated With Combination Brachytherapy and External Beam Irradiation

We assessed the impact of androgen suppressive therapy on biochemical failure in patients with intermediate risk prostate cancer treated with brachytherapy and external beam irradiation. From 1994 to 2006, 432 patients with intermediate risk prostate cancer as defined by the National Comprehensive Cancer Network were treated with low dose rate brachytherapy and external beam irradiation with or without 9 months of androgen suppressive therapy. Gleason score was 7 in 76% of cases and prostate specific antigen was 1.4 to 20 ng/ml (median 7.6). Of the patients 350 received androgen suppressive therapy and 82 did not. The biologically effective dose was 142 to 280 Gy2 (median 206). Followup was 23 to 155 months (median 56). The overall 8-year biochemical failure-free rate using the Phoenix definition in patients with vs without androgen suppressive therapy was 92% vs 92% (p = 0.4). The therapy had no significant impact on the biochemical failure-free rate in patients with Gleason score 7 (92% vs 90.5%, p = 0.55), prostate specific antigen 10 to 20 ng/ml (92% vs 100%, p = 0.32), T2b-T2c disease (89.5% vs 97%, p = 0.27) and more than 1 intermediate risk feature (90% vs 100%, p = 0.2). We addressed the relative importance of radiation dose vs hormonal therapy for intermediate risk prostate cancer. With high biologically effective dose combination treatment androgen suppressive therapy did not have a significant impact on the 8-year biochemical failure-free rate. We question its routine use in this setting.

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]

Lack of radiation dose response for patients with low-risk clinically localized prostate cancer: a retrospective analysis

Purpose: The need for dose escalation for patients with low-risk clinically localized prostate cancer remains controversial. In this study, we report our pooled institutional experience of low-risk patients treated with a range of “standard” radiation doses to assess outcome in regard to biochemical failure and to determine whether a dose-response relationship exists within this conventional dose range. Methods and Materials: Patients with low-risk clinically localized prostate cancer (T1 or T2a, Gleason grade ≤6, and prostate-specific antigen ≤10 ng/mL) treated at Joint Center for Radiation Therapy-affiliated institutions between October 1989 and September 1997 were retrospectively analyzed for freedom from biochemical failure. The dose was prescribed volumetrically with 95% normalization to between 5760 and 6900 cGy (6100 and 7300 cGy ICRU reference point dose). Patients were stratified into 3 groups with relatively equal numbers of patients (<6660, 6660, and >6660 cGy). To ensure that any differences in biochemical failure between patients at the lower and higher ends of the dose range used were not masked by analysis of the entire cohort, patients receiving ≤6500 cGy or ≥6800 cGy were subsequently analyzed separately. Biochemical failure was defined per the ASTRO consensus definition. The log-rank test was used to assess for differences in follow-up and time to biochemical failure. A Kaplan-Meier plot of time to biochemical failure for the initial 3 subgroups was generated. Results: A total of 264 patients were identified. Sixteen patients whose dose was not recorded in the database were excluded from analysis. The median follow-up was 35 months. No significant differences were found in baseline prostate-specific antigen, Gleason grade, or clinical stage among the groups. The overall actuarial rate of 5-year freedom from biochemical failure was 80.2%. By dose level, the 5-year biochemical failure-free rate was 79.2%, 78.4%, and 84.5% for <6660 cGy, 6660 cGy, and >6660 cGy, respectively. These differences were not significant. Subsequently, 45 patients receiving ≤6500 cGy were compared with 23 patients receiving ≥6800 cGy. The difference between these groups was not significant. The 5-year freedom from biochemical failure rate for the patients receiving ≤6500 cGy was 89.9%. Conclusion: Within a range of doses considered standard for treatment of low-risk clinically localized prostate cancer during an 8-year period, no improvement in biochemical freedom from failure was noted with the higher doses. The overall 5-year rate of freedom from biochemical failure is consistent with that reported by others with standard and escalated external beam doses used in this low-risk population. A prospective randomized study is necessary to define the optimal dose in this patient population.