5-year Biochemical Failure-free Survival Rate Research Articles

The influence of Gleason score ≤ 6 histology on the outcome of high-risk localized prostate cancer after modern radiotherapy

We aimed to retrospectively review outcomes in patients with high-risk prostate cancer and a Gleason score ≤ 6 following modern radiotherapy. We analyzed the outcomes of 1374 patients who had undergone modern radiotherapy, comprising a high-risk low grade [HRLG] group (Gleason score ≤ 6; n = 94) and a high-risk high grade [HRHG] group (Gleason score ≥ 7, n = 1125). We included 955 patients who received brachytherapy with or without external beam radio-therapy (EBRT) and 264 who received modern EBRT (intensity-modulated radiotherapy [IMRT] or stereotactic body radiotherapy [SBRT]). At a median follow-up of 60 (2–177) months, actuarial 5-year biochemical failure-free survival rates were 97.8 and 91.8% (p = 0.017), respectively. The frequency of clinical failure in the HRLG group was less than that in the HRHG group (0% vs 5.4%, p = 0.012). The HRLG group had a better 5-year distant metastasis-free survival than the HRHG group (100% vs 96.0%, p = 0.035). As the HRLG group exhibited no clinical failure and better outcomes than the HRHG group, the HRLG group might potentially be classified as a lower-risk group.

Assessing radiation dose for postoperative radiotherapy in prostate cancer: Real world data.

BACKGROUNDApproximately 30% of patients with localized prostate cancer (PCa) who undergo radical prostatectomy will develop biochemical recurrence. In these patients, the only potentially curative treatment is postoperative radiotherapy (PORT) with or without hormone therapy. However, the optimal radiotherapy dose is unknown due to the limited data available. AIMTo determine whether the postoperative radiotherapy dose influences biochemical failure-free survival (BFFS) in patients with PCa. METHODSRetrospective analysis of patients who underwent radical prostatectomy for PCa followed by PORT-either adjuvant radiotherapy (ART) or salvage radiotherapy (SRT)-between April 2002 and July 2015. From 2002 to 2010, the prescribed radiation dose to the surgical bed was 66-70 Gy in fractions of 2 Gy; from 2010 until July 2015, the prescribed dose was 70-72 Gy. Patients were grouped into three categories according to the total dose administered: 66-68 Gy, 70 Gy, and 72 Gy. The primary endpoint was BFFS, defined as the post-radiotherapy prostate-specific antigen (PSA) nadir + 0.2 ng/mL. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS; based on conventional imaging tests). Treatment-related genitourinary (GU) and gastrointestinal (GI) toxicity was evaluated according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Finally, we aimed to identify potential prognostic factors. BFFS, OS, CSS, and MFS were calculated with the Kaplan-Meier method and the log-rank test. Univariate and multivariate Cox regression models were performed to explore between-group differences in survival outcome measures.RESULTSA total of 301 consecutive patients were included. Of these, 93 (33.6%) received ART and 186 (66.4%) SRT; 22 patients were excluded due to residual macroscopic disease or local recurrence in the surgical bed. In this subgroup (n = 93), 43 patients (46.2%) were Gleason score (GS) ≤ 6, 44 (47.3%) GS 7, and 6 (6.5%) GS ≥ 8; clinical stage was cT1 in 51 (54.8%), cT2 in 35 (39.3%), and cT3 in one patient (1.1%); PSA was < 10 ng/mL in 58 (63%) patients, 10-20 ng/mL in 28 (30.6%), and ≥ 20 ng/mL in 6 (6.4%) patients. No differences were found in BFFS in this patient subset versus the entire cohort of patients (P = 0.66). At a median follow-up of 113 months (range, 4-233), 5- and 10-year BFFS rates were 78.8% and 73.7%, respectively, with OS rates of 93.3% and 81.4%. The 5-year BFFS rates in three groups were as follows: 69.6% (66-68 Gy), 80.5% (70 Gy) and 82.6% (72 Gy) (P = 0.12):the corresponding 10-year rates were 63.9%, 72.9%, and 82.6% (P = 0.12), respectively. No significant between-group differences were observed in MFS, CSS, or OS. On the univariate analysis, the following variables were significantly associated with BFFS: PSA at diagnosis; clinical stage (cT1 vs cT2); GS at diagnosis; treatment indication (ART vs SRT); pre-RT PSA levels; and RT dose 66 -68 Gy vs. 72 Gy (HR: 2.05; 95%CI: 1.02-4.02, P = 0.04). On the multivariate analysis, the following variables remained significant: biopsy GS (HR: 2.85; 95%CI: 1.83-4.43, P < 0.001); clinical stage (HR: 2.31; 95%CI: 1.47-4.43, P = 0.01); and treatment indication (HR: 4.11; 95%CI: 2.06-8.17, P < 0.001). Acute grade (G) 1 GU toxicity was observed in 11 (20.4%), 17 (19.8%), and 3 (8.3%) patients in each group (66-68 Gy, 70 Gy and 72 Gy), respectively (P = 0.295). Acute G2 toxicity was observed in 2 (3.7%), 4 (4.7%) and 2 (5.6%) patients, respectively (P = 0.949). Acute G1 GI toxicity was observed in 16 (29.6%), 23 (26.7%) and 2 (5.6%) patients in each group, respectively (P = 0.011). Acute G2 GI toxicity was observed in 2 (3.7%), 6 (6.9%) and 1 (2.8%) patients, respectively (P = 0.278). No cases of acute G3 GI toxicity were observed.CONCLUSIONThe findings of this retrospective study suggest that postoperative radiotherapy dose intensification in PCa is not superior to conventional radiotherapy treatment.

Low and high-dose-rate brachytherapy in combination with external beam radiotherapy for high risk prostate cancer

Background. Prostate cancer (PCa) in the Russian Federation takes the leading place in the prevalence of cancer among the male population.Objective: to investigate the effect of increasing a single focal dose in high-dose-rate brachytherapy (HDR-BT) in combination with external beam radiotherapy on biochemical failure-free survival and local control in patients with high-risk PCa. Materials and methods. The study included 350 men with PCa in the group of high and extremely high risk of progression. All patients included in the study were divided into 4 groups. Groups 1, 2 and 3 included 276 patients who received HDR-BT with a 192Ir source with a single dose per fraction: 10 Gy (n = 83), 12 Gy (n = 46) and 15 Gy (n = 147). Group 4 included 74 patients who received low-dose-rate brachytherapy with 125I sources up to a total focal dose of 110 Gy. At the 2 stage, external beam radiotherapy was a conventional fractionation (single dose of 2 Gy, total - 44-46 Gy).Results. Of 350 patients over a 5-year follow-up period, PCa recurrence was noted in 65 (18.6 %). The 3- and 5-year biochemical failure-free survival rates in the general cohort of patients were 87.4 and 81.4 %. 5-year biochemical failure-free survival was significantly higher in group 3 relative to group 4 and amounted to 89.8 and 74.2 % (p = 0.03). Increasing the dose for HDR-BT from 10 to 12 Gy per fraction significantly reduced the frequency of local relapses from 15.7 % (in group 1) to 2.2 % (in group 2) (p = 0.0001) while maintaining the level of genitourinary and gastrointestinal toxicity. Conclusion. The use of a combination of brachytherapy and external beam radiotherapy in patients with high risk PCa is highly effective in achieving local control of the tumor. The optimal fractionation regime for HDR-BT remains a matter of debate. The use of 15 Gy per fraction for HDR-BT in combination with external beam radiotherapy is the most optimal fractionation regimen in patients with high-risk PCa.

Radiotherapy for elder patients aged ≥80 with clinically localized prostate cancer – Brachytherapy enhanced late GU toxicity especially in elderly

Background and purposeElongation of life expectancy had led to marked increase in number of elderly patients with localized prostate cancer. However, the standard treatment for such patients is not well determined because of a high prevalence of comorbidities and slow growth of prostate cancer. The aim of this study is to examine the feasibility of radiotherapy for elderly patients aged ≥80 years. Materials and methodsWe compared 96 patients aged ≥80 years and 2333 younger patients (aged 60–79 years) using multi-institutional data included cT1-T4N0M0 prostate cancer treated with 902 external beam radiotherapy (EBRT) and 1527 brachytherapy (BT). ResultsThe 5-year biochemical failure-free survival rate was similar between elderly ≥80 years and younger control (91.3% vs. 85.9%, p = 0.6171) (100%, 92.9%, 82.4% and 96.3%, 93.7%, 89% for low, intermediate and high risk group), and for the prostate cancer-specific survival rate (100% and 99.3%, p = 0.6171). The accumulated incidence of late gastrointestinal (GI) at 5 years was also similar between elderly and younger patients (3.5% vs. 2.5%, p = 0.6857). Brachytherapy improved biochemical control rate and reduced GI toxicity compared with EBRT, however, enhanced late genitourinary (GU) toxicity, especially in elderly patients. Elderly received brachytherapy showed highest rate of late GU toxicity grade ≥2 of 22.1% than the younger counterparts of 12.7% at 5 years, whereas younger patients treated with EBRT had 2.4% and elderly EBRT had 2.7% (p < 0.0001). ConclusionElderly patients aged ≥80 years showed equivalent biochemical control, prostate cancer-related survival, and gastrointestinal toxicity profiles to younger patients. Meticulous care should be required for brachytherapy enhanced late GU toxicity, especially in elderly patients aged ≥80 years.

Influence of transitioning of planning techniques in high-dose-rate brachytherapy monotherapy for clinically localized prostate cancer from two- to three-dimensional planning

PurposeThe purpose of this study was to examine the influence of transitioning treatment planning techniques in high-dose-rate interstitial brachytherapy monotherapy for localized prostate cancer. Methods and MaterialsWe compared 113 patients treated with initial two-dimensional treatment planning (2D: 74% received 54 Gy/nine fractions) to 240 patients treated with three-dimensional planning (3D: 70 CT image-guided 3D [CT-3D]: 84% 45.5 Gy/seven fractions and 170 MRI image-guided [MRI-3D]: 87% received 49 Gy/nine fractions). ResultsThe actuarial 5-year biochemical failure-free survival rates for 2D and 3D planning were 88.4% and 95.1% (p = 0.0285 between 2D and 3D) (89.4% in CT-3D and 97.5% in MRI-3D), respectively; the rates for 2D and 3D planning were not available and 100% in the low-risk group (100% and 100%), 97.7% and 94.5% (p = 0.7626) (85.1% and 100%) in the intermediate-risk group, and 82.5% and 94.4% (p = 0.0507) (93.8% and 94.7%) for the high-risk group. Late gastrointestinal (GI) toxicity Grade 1, Grade 2, and Grade 3 was found in 13%, 4%, and 1% in 2D, whereas 8%, 2%, and 0% in 3D group (p = 0.0699), respectively. 3D decreased GI toxicity Grade 2 ≤ than 2D (19% and 10%, p = 0.0169). Late genitourinary toxicity Grade 1, Grade 2, and Grade 3 was 21%, 12%, and 3% for 2D and 32%, 18%, and 3% for 3D, respectively (p = 0.0217). ConclusionsThe 3D technique has the potential to reduce GI toxicity and improve biochemical control rate compared to 2D planning, whereas 3D resulted in increased mild genitourinary toxicity.

High-dose-rate brachytherapy monotherapy versus low-dose-rate brachytherapy with or without external beam radiotherapy for clinically localized prostate cancer

BackgroundTo compare the outcome of high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy and low-dose-rate brachytherapy (LDR-BT) with or without external beam radiotherapy (EBRT) for localized prostate cancer. Methods and materialsWe compared 352 patients treated with HDR-BT as monotherapy (median follow-up time 84 months, NCCN risk classification; low: intermediate: high = 28:145:179) and 486 patients with LDR-BT with or without EBRT (90 months, 194:254:38). HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. LDR-BT excluded patients with T3b–T4 tumor and initial PSA >50 ng/ml. Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias. ResultsThe actuarial 5-year biochemical failure-free survival rates (bNED) were 92.9% and 95.6% (p = 0.25) in the HDR-BT and LDR-BT groups, respectively, and it was 100% and 97.3% (p = 0.99) in the low-risk, 95.6% and 94.3% (p = 0.19) in the intermediate, 89.6% and 94.9% (p = 0.26) in the high-risk groups, and 93.1% and 94.9% (p = 0.98) in selected high-risk group excluding T3b-4 and initial PSA ≥50. IPTW correction also indicated no difference in bNED between LDR-BT and HDR-BT groups. LDR-BT showed a higher incidence of genitourinary (GU) toxicity grade ≥2 than that of HDR-BT in the acute phase and grade 1 toxicity in late phase. Acute GU toxicity grade ≥1 predicted late GU toxicity grade ≥2. External beam radiotherapy plus LDR-BT elevated GI toxicity than LDR-BT only group. Accumulated incidence of late grade ≥2 GU and GU toxicity was equivalent between HDR-BT and LDR-BT. No grade 4 or 5 toxicities were detected in either modality. ConclusionHDR-BT monotherapy showed an equivalent outcome to that of LDR-BT with or without EBRT for low-, intermediate- and selected high-risk patients. LDR-BT showed equivalent incidence of grade ≥2 late GI and GU toxicities and higher grade ≥2 acute GU toxicity as that of HDR-BT as a monotherapy.

Comparison of three moderate fractionated schedules employed in high-dose-rate brachytherapy monotherapy for clinically localized prostate cancer

BackgroundHerein, we report the outcomes of 3 schedules of high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy for localized prostate cancer. Patients and methodsA total of 347 patients were treated with 45.5 Gy/7 fractions (n = 86; 45.5 Gy arm, median follow-up time 131 months), 49 Gy/7 fractions (n = 149; 49 Gy arm, 75.9 months), and 54 Gy/9 fractions (n = 112; 54 Gy arm, 68 months). ResultsThe actuarial 5-year biochemical failure-free survival rates were 86.8%, 94.1%, and 88.5% (p = 0.2023) for the 45.5 Gy, 49 Gy, and 54 Gy arms in the high-risk group; 90.4%, 100%, and 97.4% (p = 0.0818) in the intermediate-risk group; and not available, 100%, and 100% in the low-risk group, respectively. The 5-year distant metastasis-free (and overall) survival rates were 94.4%, 98.2%, and 96.3% (100%, 92.8%, and 99.1%) for the 45.5 Gy, 49 Gy, and 54 Gy arms (p = 0.5454 and p = 0.0028), respectively. At 5 years, accumulated incidence of grade ≥2 gastrointestinal toxicity was 1.2%, 2.7%, and 3.4% for the 45.5 Gy, 49 Gy, and 54 Gy arms (p = 0.5605), respectively. For genitourinary toxicity, the 49 Gy arm showed a higher grade ≥2 toxicity of 20.5% than those observed in the 45.5 Gy (2.4%) and 54 Gy arms (10.1%). No grade 4 or 5 of either type of toxicity was detected. ConclusionsThe 3 schedules showed equivocal outcomes in each risk group, with different toxicity profiles. HDR-BT monotherapy with these schedules is an acceptable treatment option for localized prostate cancer.

High-dose-rate brachytherapy boost for prostate cancer treatment: Different combinations of hypofractionated regimens and clinical outcomes

PurposeTo report the outcomes of our high-dose-rate brachytherapy (HDR-BT) boost experience in localized prostate cancer treated with different combinations of radiation doses and fractionation. Material and methodsBetween 1999 and 2011, 832 patients were treated with different regimens of external beam radiotherapy (EBRT) and HDR-BT. These regimens were converted into three biologically effective dose (BED) groups. The biochemical failure-free survival (BFFS), reported with the phoenix definition and prostate-specific antigen (PSA) >0.2ng/ml at 5-year, genitourinary (GU) and gastrointestinal (GI) toxicities were compared between the groups. ResultsThe 5-, 10-year BFFS for the entire cohort were 94.6% and 92.5%, for overall survival (OS) 96.1% and 80.3% and for prostate cancer-specific survival (PCSS) 99.5% and 97.8%. The percentage of patients with a 5-year PSA level <0.2ng/ml was 68.6%, 78.7% and 86.7% in the BED group of <250, 250–260 and >260Gy (p=0.005) while the 5-year BFFS rates according to phoenix definition were 97.3%, 94.3% and 94.9% for BED group <250, 250–260 and >260Gy (p=0.453). On multivariate logistic regression, patients in the BED>260Gy group were significantly more likely to remain free from 5-year PSA values ≥0.2ng/mL compared with those in the BED<250Gy group (OR: 0.350, p=0.011). Grade≥3 acute GU toxicity was reported in 2 patients (4.7%) for BED>260Gy while grade≥3 late GU toxicity was reported in 6 (1.7%) and 9 (4.9%) patients for 250–260Gy and >260Gy BED groups. ConclusionsThe increase in BED with the hypofractionated regimens correlates with an improvement in biochemical control with of urinary toxicity. This increase in urinary toxicity is small and clinically acceptable.

Correlations of post-implant regional dosimetric parameters at 24 hours and one month, with clinical results of low-dose-rate brachytherapy for localized prostate cancer.

PurposeTo evaluate the correlations of post-implant regional dosimetrics at 24 hours (24 h) and 1 month after implant procedures, with clinical outcomes of low-dose-rate (LDR) brachytherapy for localized prostate cancer.Material and methodsBetween January 2008 and December 2014, 130 consecutive patients treated for localized prostate cancer, receiving definitive iodine-125 (125I) brachytherapy treatment were retrospectively analyzed. All patients underwent post-implant CT imaging for dosimetric analysis at 24 h and 1 month after implantation procedure. Prostate contours were divided into quadrants: anterior-superior (ASQ), posterior-superior (PSQ), anterior-inferior (AIQ), and posterior-inferior (PIQ). Predictive factors and cut-off values of biochemical failure-free survival (BFFS) and toxicities of LDR brachytherapy were analyzed.ResultsThe median follow-up time was 69.5 months. Seven patients (5.4%) had biochemical failure. The 3-year and 5-year BFFS rates were 96.7% and 93.1%, respectively. On multivariate analysis, prostate-specific antigen and Gleason score were significant prognostic factors for biochemical failure. D90 (the minimal dose received by 90% of the volume) of PSQ and PIQ at 24 h, and D90 of PSQ at 1 month were also significant factors. The cut-off values of PSQ D90 were 145 Gy at 24 h and 160 Gy at 1 month. D90 of the whole prostate was not significant at 24 h and at 1 month. D90 of PSQ at 1 month was a significant factor for rectal hemorrhage.ConclusionsPost-implant D90 of PSQ is significantly associated with BFFS for localized prostate cancer not only at 1 month, but also at 24 hours. D90 of PSQ at 1 month is also a significant factor for rectal hemorrhage.

Image-guided high-dose-rate brachytherapy boost to the dominant intraprostatic lesion using multiparametric magnetic resonance imaging including spectroscopy: Results of a prospective study

PurposeTo evaluate the long-term outcomes of image-guided high-dose-rate (HDR) brachytherapy boost to the dominant intraprostatic lesion (DIL) using multiparametric magnetic resonance imaging (MRI), including spectroscopy (MRI/magnetic resonance spectroscopy [MRS]). Methods and MaterialsBetween December 2009 and March 2011, 20 patients with intermediate-risk prostate cancer underwent multiparametric MRI/MRS protocol before treatment. All patients were treated with an external beam radiotherapy dose of 40 Gy, combined with an HDR brachytherapy boost of 15 Gy. Concurrently, the DIL received a boost of 18 Gy. Missing data during followup were handled with multiple imputations. ResultsThe median followup was 62 months (range, 23–71 months). Six patients (31%) were classified as favorable intermediate risk and 13 patients (69%) as unfavorable intermediate risk. One patient experienced a prostate-specific antigen biochemical failure, and the 5-year biochemical failure-free survival rate was of 94.7%. The mean International Prostate Symptom Score rose from 7, with respect to baseline, to 10.42 1 month after treatment, and rapidly decreased to 6.97 after 3 months. Grade 1, 2, and 3 acute genitourinary toxicities were reported in 13 (68%), 3 (16%), and 1 (5%) patients, respectively. Grade 1 and 2 late genitourinary toxicities were reported in 9 (53%) and 3 (18%) patients, respectively. Only grade 1 acute and late gastrointestinal toxicities were reported in 4 (21%) and 3 (18%) patients, respectively. ConclusionsDelivering an HDR brachytherapy boost to the DIL using image-guided multiparametric MRI/MRS is feasible with good outcomes for biochemical control, acute and late toxicities, and dosimetric constraints for critical organs.

Allegheny General Hospital experience with LDR prostate brachytherapy comparing Pd-103 with I-125.

274 Background: To report a retrospective review of a single institution’s experience treating patients with localized adenocarcinoma of the prostate with low-dose rate brachytherapy (LDR-BT) comparing clinical outcomes at 5 years of patients treated with Pd-103 vs. I-125. Methods: 332 hormone-naïve patients with localized adenocarcinoma of the prostate were treated with LDR-BT without androgen deprivation therapy (ADT) between 1998-2008 at Allegheny General Hospital. 300 patients had more than 12 months of follow-up and were included in the statistical analysis. 40 patients (13%) were treated with Pd-103 and 260 (87%) were treated with I-125. The decision to treat with Pd-103 was based on physician preference and pretreatment urinary AUA score. Both treatment groups (Pd-103 vs. I-125) were otherwise stratified similarly with regards to median patient age (65 vs. 65), NCCN low-risk category (87.5% vs. 89.9%), Gleason score 6 (92.5% vs. 88.1%), Clinical T1c (85% vs. 79.9%), pretreatment median PSA (5.9 vs. 5.6), and pretreatment mean AUA score (8 vs. 6.5). All pathology was reviewed by a single genitourinary pathologist. All prostate seed implants were performed by a single radiation oncologist. Results: Median follow-up was 67 months for Pd-103 patients and 80 months for I-125 patients. Mean D90 for the Pd-103 group was 140.7 Gy versus 170.9 Gy in the I-125 group. There was one biochemical failure in the Pd-103 group and 21 biochemical failures in the I-125 group. 5-year biochemical failure free-survival rates were 95.7% for the Pd-103 group and 90.1% for the I-125 group (p=0.13). Conclusions: Prior studies have shown no difference in outcomes between patients treated with Pd-103 and I-125 for early stage prostate cancer. Therefore the choice of isotope in LDR-BT is based on urologist and/or radiation oncologist preference and patient clinical presentation (AUA score). Our institution’s experience indicates a trend towards increased rates of biochemical failure in a homogenous group of patients treated with I-125 compared to Pd-103. Due to the retrospective nature of our study as well as the limited number of patients, this requires validation in a prospective trial.

Combined brachytherapy and external beam radiotherapy without adjuvant androgen deprivation therapy for high-risk prostate cancer

BackgroundTo report the outcomes of patients treated with combined iodine-125 (I-125) brachytherapy and external beam radiotherapy (EBRT) for high-risk prostate cancer.MethodsBetween 2003 and 2009, I-125 permanent prostate brachytherapy plus EBRT was performed for 206 patients with high-risk prostate cancer. High-risk patients had prostate-specific antigen ≥ 20 ng/mL, and/or Gleason score ≥ 8, and/or Stage ≥ T3. One hundred and one patients (49.0%) received neoadjuvant androgen deprivation therapy (ADT) but none were given adjuvant ADT. Biochemical failure-free survival (BFFS) was determined using the Phoenix definition.ResultsThe 5-year actuarial BFFS rate was 84.8%. The 5-year cause-specific survival and overall survival rates were 98.7% and 97.6%, respectively. There were 8 deaths (3.9%), of which 2 were due to prostate cancer. On multivariate analysis, positive biopsy core rates and the number of high-risk factors were independent predictors of BFFS. The 5-year BFFS rates for patients in the positive biopsy core rate <50% and ≥50% groups were 89.3% and 78.2%, respectively (p = 0.03). The 5-year BFFS rate for patients with the any single high-risk factor was 86.1%, compared with 73.6% for those with any 2 or all 3 high-risk factors (p = 0.03). Neoadjuvant ADT did not impact the 5-year BFFS.ConclusionsAt a median follow-up of 60 months, high-risk prostate cancer patients undergoing combined I-125 brachytherapy and EBRT without adjuvant ADT have a high probability of achieving 5-year BFFS.

Comparison of Preplanning and Intraoperative Planning for I-125 Prostate Brachytherapy

To compare two widely used permanent prostate brachytherapy techniques, preplanning and intraoperative planning, based on postimplant dosimetry, toxicity and biochemical outcomes. Between 2003 and 2006, 665 men with localized prostate cancer were treated with permanent interstitial implantation. The first 227 consecutive men were treated with the preplanning technique, followed by 438 men treated with the intraoperative technique. Late toxicity was scored by the Common Terminology Criteria for Adverse Events v.4.0. Biochemical failure was defined as a prostate-specific antigen increase of more than 2 ng/ml above the nadir value excluding a benign bounce. Univariate and multivariate analyses were performed to identify the variables associated with biochemical failure-free survival. Postimplant target coverage was similar in the two groups, with a small difference in risk organ doses. Mean V100 was 96.3 vs. 96.7% (P = 0.205), D90 was 119.6 vs. 119.4% (P = 0.884), urethral D10 was 157.5 vs. 146.1% (P = 0.010), rectal V100 was 0.57 vs. 0.43 cc (P = 0.002) in the preplanning and intraoperative planning groups, respectively. Acute and late Grade 3 genitourinary and gastrointestinal toxicities were <1% for both methods. The 5-year biochemical failure-free survival rate was 95.4% for the preplanning and 94.0% for the intraoperative planning group (P = 0.776). Multivariate analysis revealed Gleason score, biopsy positive rate and V100 to be predictors of biochemical failure-free survival, while the planning technique was not significant. This large-scale analysis of high-quality implants revealed similar postimplant dosimetry, toxicity profiles and biochemical failure-free survival for the preplanning and intraoperative planning methods.

1479 CLINICALLY SIGNIFICANT URETHRAL STRICTURE AND/OR SUBCLINICAL URETHRAL STRICTURE AFTER HIGH-INTENSITY FOCUSED ULTRASOUND PARADOXICALLY CORRELATES WITH DISEASE-FREE SURVIVAL IN LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized VII1 Apr 20121479 CLINICALLY SIGNIFICANT URETHRAL STRICTURE AND/OR SUBCLINICAL URETHRAL STRICTURE AFTER HIGH-INTENSITY FOCUSED ULTRASOUND PARADOXICALLY CORRELATES WITH DISEASE-FREE SURVIVAL IN LOCALIZED PROSTATE CANCER Teruo Inamoto, Kazumasa Komura, Peter Black, Yoji Katsuoka, Toshikazu Watsuji, and Haruhito Azuma Teruo InamotoTeruo Inamoto Takatsuki, Japan More articles by this author , Kazumasa KomuraKazumasa Komura Takatsuki, Japan More articles by this author , Peter BlackPeter Black Vancouver, Canada More articles by this author , Yoji KatsuokaYoji Katsuoka Takatsuki, Japan More articles by this author , Toshikazu WatsujiToshikazu Watsuji Takatsuki, Japan More articles by this author , and Haruhito AzumaHaruhito Azuma Takatsuki, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2000AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies have reported the frequency of urethral stricture (US) after high-intensity focused ultrasound (HIFU), but the association between development of US and disease-free survival has never been studied. The aim of this study is to demonstrate a correlation between the occurrence of post-therapy US and disease free survival after HIFU for localized prostate cancer. METHODS The inclusion criteria for treatment were clinical stage T1-T2N0M0 prostate cancer. Between 2004 and 2008, 153 consecutive patients undergoing HIFU at our institution were enrolled into a database. We analyzed the data of 144 patents who underwent HIFU as the primary therapy, excluding the data of 9 patients who were treated for salvage. Treatment failure was defined according to the Phoenix criteria, and the disease-free survival rate (DFSR) was evaluated using this definition. Patients were divided into two subgroups according to whether or not they developed a urethral stricture (US) or a subclinical urethral stricture (SCUS) during follow-up. In the present study, clinically insignificant bladder outlet obstruction requiring transient catheterization, which did not need any further intervention, was defined as subclinical urethral stricture (SCUS). RESULTS The median follow-up time was 47 months (range 2-70). US/SCUS occurred in 58 (40.3%) patients, of whom 30 (20.8%) were SCUS, 27 (18.8%) grade 1-3 US and 1 (0.7%) grade 4 US. The median time to development of US/SCUS was 3 months (range 1-8). There was a significant association with development of US/SCUS and decreased PSA nadir level (p < 0.001). The 5-year biochemical failure-free survival rate (BFSR) was 67.8% and demonstrated a statistically significant difference between patients who did (76.7%) and did not (55.8%) develop US/SCUS (p = 0.004). The risk of biochemical failure was increased approximately 3-fold in patients without development of US/SCUS compared to patients with development of US/SCUS (HR: 3.003, 95% CI: 1.371 - 6.575, p = 0.006). On Cox regression analysis, development of US/SCUS was found to be an independent predictor of DFSR, along with clinical stage and PSA nadir level. CONCLUSIONS This present study has demonstrated the significance of US/SCUS, the most common complication of HIFU, as a prognostic factor for treatment outcome in patients undergoing HIFU for localized prostate cancer. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e599-e600 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Teruo Inamoto Takatsuki, Japan More articles by this author Kazumasa Komura Takatsuki, Japan More articles by this author Peter Black Vancouver, Canada More articles by this author Yoji Katsuoka Takatsuki, Japan More articles by this author Toshikazu Watsuji Takatsuki, Japan More articles by this author Haruhito Azuma Takatsuki, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as ≥T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: ≥T3, prostate-specific antigen level >20 ng/mL, GS ≥8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.

Impact of Common Iliac Nodal Treatment on Radiation Outcomes in Localized Prostate Cancer

The Radiation Therapy Oncology Group 9413 trial has shown an improvement in progression-free survival (PFS) with external beam radiotherapy that included the pelvic nodes. In clinical practice, two pelvic field size designs are in use. We examined the effect of differences in the level of pelvic nodal coverage using three-dimensional conformal radiotherapy on biochemical failure-free survival (BFFS) and PFS in early-stage prostate cancer. The patients were identified retrospectively who had undergone whole pelvis (WP) or minipelvis (MP) three-dimensional conformal radiotherapy. Biochemical failure was defined as the nadir prostate-specific antigen (PSA) level plus 2 ng/mL. Of the 669 patients identified, 384 had undergone MP (57%) and 285 WP (42%) treatment, with a median PSA follow-up of 56 months. Of the 669 patients, 11%, 35%, and 54% were at low, intermediate, and high risk, respectively. The median dose was 75 Gy for the MP and 71 Gy for the WP groups. Of the MP and WP groups, 52% and 36% underwent hormonal therapy. The median BFFS and 5-year BFFS rate was 128 months and 73% for the MP group and 96 months and 58% for the WP group. The median PFS and 5-year PFS rate was 128 months and 72% for the MP group and 83 months and 56% for the WP group. Multivariate analysis revealed no difference between MP and WP treatment. However T stage, pretreatment PSA level, and Gleason score were significant predictors of BFFS and PFS. We observed no difference in outcomes between patients undergoing WP versus MP using three-dimensional conformal radiotherapy. Therefore, the exclusion of the common iliac lymph nodes in the treatment of patients with high-risk prostate cancer might be acceptable.

Prostate-Specific Antigen Control with Low-Dose Adjuvant Radiotherapy for High-Risk Prostate Cancer

To analyze the prostate-specific antigen (PSA) outcome after low-dose adjuvant RT at a single institution, because the role and optimal dose of external beam radiotherapy (RT) after radical prostatectomy for prostate cancer remain controversial. We retrospectively identified 65 men who had received low-dose adjuvant RT (median 50 Gy) for microscopically positive margins with an undetectable postoperative PSA from 1990 to 2004. Biochemical failure-free survival was the primary endpoint. Biochemical failure was defined as two consecutive PSA increases to greater than 0.2 ng/mL. At a median follow-up of 5 years, 2 men had developed distant metastasis, 2 had local recurrence, and 2 had died (neither attributable to prostate cancer). Biochemical failure had occurred in 7 men (11%). The 5 and 8-year rate of biochemical failure-free survival was 87%. A greater Gleason score (P = 0.04) and seminal vesicle invasion (P = 0.04) predicted significantly for increased biochemical failure on univariate analysis. No single factor was significant on multivariate analysis. Men with a Gleason score of 7 or less had a 5-year biochemical failure-free survival rate of more than 90%. In contrast, those with a Gleason score of 8 or more had a 50% risk of biochemical failure at 5 years. Acute bowel or bladder toxicity (all grade 2 or less) developed in 25%. Two men developed chronic urethral stricture requiring dilation, and 34 (51%) developed surgery-related toxicity that persisted throughout and after RT. Low-dose RT is well tolerated and can potentially provide PSA control in men with Gleason score 7 or less disease with positive surgical margins after radical prostatectomy.

Role of external beam radiotherapy with low-dose-rate brachytherapy in treatment of prostate cancer

Objectives To report a single-institution experience and analysis of the role of supplemental external beam radiotherapy (EBRT) with brachytherapy. EBRT is often used in addition to low-dose-rate brachytherapy in the treatment of prostate cancer, particularly for disease with adverse features. Methods A cohort of 189 consecutive patients, who had undergone low-dose-rate brachytherapy at our institution and who had demographic, disease, and treatment information and a minimum of 2 years of follow-up available, constituted the study group. This cohort was divided into two major groups according to the use of supplemental EBRT. Using two successive prostate-specific antigen rises greater than 1 ng/mL as the definition of failure, biochemical failure-free survival curves were constructed for the EBRT and no-EBRT groups and compared using the log-rank test. Additionally, a multivariate analysis of all major disease and treatment factors was performed using the Cox proportional hazards model. Results Despite the greater proportion of adverse disease factors in the EBRT group, the 5-year biochemical failure-free survival rate in the EBRT versus no-EBRT groups was 80% versus 59%, respectively ( P <0.01). On multivariate analysis, the only factor reaching significance in predicting biochemical control was the use of EBRT ( P = 0.043). Conclusions In our study, the addition of EBRT conferred a significant biochemical control advantage when added to low-dose-rate brachytherapy. Because our study was not designed to permit detailed subset analyses, more work is needed to determine the precise brachytherapy population that will benefit from this use of supplemental EBRT.