Brachytherapy Monotherapy Research Articles

Quality of life after high-dose rate brachytherapy monotherapy for prostate cancer.

278 Background: There is little information in the literature on health-related quality-of-life (HRQOL) changes due to high-dose-rate (HDR) brachytherapy monotherapy for prostate cancer. Methods: We conducted a prospective study of HRQOL changes due to HDR brachytherapy monotherapy for low risk or favorable intermediate risk prostate cancer. Forty-nine of 84 (58%) patients who were treated between February 2011 and April 2013 completed 50 questions comprising the Expanded Prostate Cancer Index Composite (EPIC) before treatment and 6 and/or 12 months after treatment. Results: Six months after treatment, there was a significant decrease (p<0.05) in EPIC urinary, bowel, and sexual scores, including urinary overall, urinary function, urinary bother, urinary irritative, bowel overall, bowel bother, sexual overall, and sexual bother scores. By one year after treatment, all EPIC scores had increased and were not significantly different from baseline values. Conclusions: HDR brachytherapy monotherapy is well-tolerated in patients with low and favorable intermediate risk prostate cancer. Urinary, bowel, and sexual domain scores returned to close to baseline 12 months after treatment.

Impact of national guidelines on brachytherapy monotherapy practice patterns for prostate cancer

In 1999 and 2000, 2 national guidelines recommended brachytherapy monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high-risk prostate cancer. This study examined rates of BT use before and after publication of these guidelines, as compared with 4 other treatment options. From 1990 to 2011, 8128 men with localized prostate cancer (≤ T3cN0M0) were treated definitively within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry with 1 of 5 primary treatments: BT, external beam radiotherapy (EBRT), EBRT with androgen deprivation therapy, EBRT+BT, or radical prostatectomy. Men were categorized into low-, intermediate-, and high-risk groups based on the guidelines' risk-group definitions. Within each risk group, logistic regression was used to estimate odds ratios (OR) comparing BT with other treatment options between the 1990-1998 and 1999-2011 periods, adjusting for age, disease characteristics, and clinic type. In total, 1117 men received BT alone for low- (n = 658), intermediate- (n = 244), or high-risk disease (n = 215). BT comprised 6.1% of all treatments in 1990-1998 versus 16.6% in 1999-2011 (P < .01). The odds of BT use remained increased after adjusting for potential confounders (OR = 3.06; P < .001) and was seen among low- (OR = 4.52; P < .001), intermediate- (OR = 2.67; P < .001), and even high-risk groups (OR = 2.11; P < .001). National guidelines did not appear to influence practice patterns, as BT monotherapy use increased relative to other treatments from the 1990-1998 to 1999-2011 periods in unfavorable risk groups including men with high-risk prostate cancer.

Mid-term outcome of permanent prostate iodine-125 brachytherapy in Japanese patients

To analyze mid-term oncological outcomes of low-dose rate brachytherapy in Japanese patients. Between 2003 and 2010, 604 consecutive patients with clinically localized prostate cancer were treated with low-dose rate brachytherapy at Jikei University Hospital in Tokyo, Japan. Median follow up was 48 months. Of these patients, 260 (43%) were treated with neoadjuvant therapy, 45 (7.5%) with adjuvant hormonal therapy and 75 (12.4%) with supplemental external beam radiation therapy. Biochemical recurrence was defined as the prostate-specific antigen nadir plus 2 ng/mL. Of the 604 patients, 219 (36.2%) were low risk, 361 (59.8%) were intermediate risk and 24 (4.0%) had high-risk disease. The median biologically effective dose was 174.4 Gy2. At 8 years, biochemical recurrence-free survival, cancer-specific survival, and overall survival were 82.2%, 100% and 95.6%, respectively. Biochemical recurrence-free survival at 8 years was 89.9%, 79.4% and 52.5%, for the low-, intermediate-, and high-risk groups, respectively. Biochemical recurrence-free survival for the high-risk group was significantly lower than the low- and intermediate-risk groups (P < 0.001). Biochemical recurrence-free survival did not differ significantly by biologically effective dose stratification. In multivariate analysis, younger age (P = 0.045), higher prostate-specific antigen (P = 0.004), higher Gleason score (P = 0.006) and higher clinical T stage (P = 0.008) were significant covariates associated with biochemical recurrence. The addition of hormonal therapy or external beam radiation therapy was associated with significantly better outcomes than low-dose rate brachytherapy monotherapy (P = 0.0021 and 0.010). Just four patients experienced G3 genitourinary or gastrointestinal toxicity. Low-dose rate brachytherapy results in excellent mid-term oncological outcomes and acceptable toxicity in Japanese patients. In our experience, biologically effective dose does not represent a significant predictor for biochemical recurrence.

High-dose-rate brachytherapy with or without intensity modulated radiation therapy as salvage treatment for an isolated, gross local recurrence of prostate cancer post-prostatectomy

To evaluate the use of high-dose-rate (HDR) brachytherapy±intensity modulated radiation therapy (IMRT) as salvage therapy for patients with an isolated, gross local recurrence of prostate cancer after radical prostatectomy. Between October 2009 and May 2013, the authors treated six patients with salvage iridium-192 HDR brachytherapy±IMRT for biopsy-proven, recurrent prostate cancer post-prostatectomy. In each patient, a pelvic MRI scan or CT scan demonstrated a nodule (range 1.6, 4.7cm) in the prostate bed. Although prostate-specific antigen values were 0.2-9.5ng/mL at the time of salvage brachytherapy, there was no pelvic adenopathy on CT or MRI scan, and a bone scan was negative in all cases. Five patients were treated with IMRT to 4500-5040cGy in 25-28 fractions to the prostate bed followed by two 950cGy HDR brachytherapy fractions separated by 1-2weeks. A sixth patient underwent HDR brachytherapy monotherapy consisting of 3800cGy in four fractions over 3 days. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median followup was 9 months (range 3, 40 months). All six patients have been free of androgen deprivation therapy and have an undetectable prostate-specific antigen. One patient developed late Grade 2 urinary incontinence. There was no late grade ≥2 gastrointestinal toxicity. HDR brachytherapy±IMRT is a safe and effective salvage therapy option for an isolated, gross local recurrence of prostate cancer after radical prostatectomy and merits further study.

Dosimetric quality and evolution of edema after low-dose-rate brachytherapy for small prostates: Implications for the use of newer isotopes

To characterize prostate swelling and dosimetry in patients with small prostate volumes (PVs) undergoing brachytherapy. We studied 25 patients with PV <25 cc (range, 15.1-24.8) and 65 patients with PV ≥25 cc (range, 25.0-66.2) based on three-dimensional ultrasound contours who underwent brachytherapy monotherapy with intraoperative planning. Postoperative Days 1 and 30 dosimetry was done by CT-MRI fusion. Small PVs had greater Day 1 swelling than large PVs (32.5% increase in volume vs. 23.7%, p= 0.04), but by Day 30, swelling was minimal and not significantly different (p= 0.44). Small PVs had greater seed and needle densities at implant (p < 0.001). Rectal and urethral doses were nearly identical by Day 30 (small PV rectum receiving 100% of the prescription dose [145Gy] [V100]= 0.32 cc; large PV rectum V100= 0.33 cc, p= 0.99; small PV urethra receiving 150% of the prescription dose [145Gy] [V150]=0.20, large PV urethra V150=0.20, p= 0.91). Swelling at Day 1 created some cool implants (rate dose that covers 90% of the prostate volume [D90 <140Gy=12.0% and 9.4% for the small and large PV groups, respectively, p= 0.71), but Day 30 planning target volume coverage was excellent (rate D90 <140Gy=0% for both groups). Although smaller prostates have greater Day 1 swelling, good Day 30 dosimetry can be achieved, making them excellent candidates for (125)I seeds (half-life [t½]=60 days). Smaller prostates may be suboptimal for shorter t½ sources such as (131)Cs (t½=9.7days), in which the majority of the dose may be delivered to an edematous gland, unless the planning is adjusted to anticipate the edema.

Biochemical outcomes for patients with intermediate risk prostate cancer treated with I-125 interstitial brachytherapy monotherapy

Background and purposeRoutine use of I-125 interstitial brachytherapy (BT) alone in intermediate risk (IR) prostate cancer is controversial. It is often combined with external beam radiotherapy (EBRT). The biochemical outcome of a large cohort of only IR disease treated with BT monotherapy is reported. Materials and methodsBetween 2003 and 2007, 615 patients with Memorial Sloan-Kettering Cancer Centre (MSKCC) defined IR disease (one risk factor only-T2b, or Gleason score (GS) 7, or raised initial PSA (iPSA) 10.1–20ng/ml) were treated with BT monotherapy. ASTRO (3 consecutive rises) and Phoenix (nadir plus 2) criteria defined biochemical failure. Potential prognostic factors (pre- and post-implant dosimetric indices, GS 3+4 versus 4+3, androgen deprivation therapy (ADT)) were analysed. ResultsMedian follow-up was 5.0years. Forty-three patients had stage T2b, 180 had raised iPSA, 392 had GS 7 disease. ADT was received by 108 patients. The 5-year biochemical no evidence of disease (bNED) rates are 87.3% (by ASTRO), 88.6% (by Phoenix). Stratification by risk factor (T2b, GS7, raised iPSA) demonstrated raised iPSA to have poorer outcome only by Phoenix criteria (p=0.0002). Other potential prognostic variables were non-significant. ConclusionGood rates of biochemical control can be achieved in the medium term with BT monotherapy in IR disease. Raised iPSA correlated with a poorer outcome.

Impact of prostate cancer national guidelines on brachytherapy monotherapy practice patterns.

5024 Background: In 1999, the American Brachytherapy Society (ABS) recommended brachytherapy monotherapy (BT) be limited to low-risk prostate cancer, in part because a high-impact 1998 publication suggested that intermediate or high-risk disease had worse outcomes with BT than with external beam radiation (EBRT) or radical prostatectomy (RP). We studied temporal patterns of BT use before and after the 1999 ABS published guidelines as compared with 4 other treatment options. Methods: A retrospective analysis was performed of all men with T1c-T3cN0M0 prostate cancer treated definitively in the United States from 1990 to 2011 in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Logistic regression was used to estimate adjusted odds ratios (AOR) comparing BT use with other treatment groups between the 1990-1998 and 1999-2011 periods, controlling for age, disease characteristics, and clinic site type. Results: 8128 men received BT (n=1117), BT+EBRT (n=313), EBRT alone (n=596), EBRT+androgen deprivation therapy (ADT, n=613), or RP (n=5489) for modified D’Amico low (n=3506), intermediate (n=2938) or high-risk (n=1684) disease. By t-tests, BT patients were younger than either EBRT or EBRT+ADT patients (both p&lt;0.001), older than RP patients (p&lt;0.001), and had lower risk disease than men in any of the four treatment groups (all Cochran-Mantel-Haenszel chi-square p&lt;0.001). BT comprised 6.1% and 16.6% of all treatments in 1990-1998 and 1999-2011, respectively (Pearson p&lt;0.01). The odds of BT use remained increased after adjusting for potential confounders (AOR 4.50, p&lt;0.001). Increased BT use was seen only among low (AOR 5.06, p&lt;0.001) and intermediate-risk patients (AOR 4.59, p&lt;0.001). Among men with low or intermediate-risk disease, BT use increased compared with EBRT (AORLOW 10.00; AORINT 12.66, both p&lt;0.001), EBRT+ADT (AORLOW 2.90, p=0.0037; AORINT 2.15, p=0.0041) and RP (AORLOW 4.76; AORINT5.10, both p&lt;0.001). Conclusions: Despite national guidelines to the contrary, brachytherapy monotherapy for intermediate-risk prostate cancer increased over time relative to other treatments. Further studies are needed to identify factors that contribute to this evidence-practice gap.

Dose-escalated adaptive image-guided radiotherapy versus high-dose-rate brachytherapy monotherapy for low-risk prostate cancer.

145 Background: Both IGRT and HDR are used for definitive treatment of low-risk prostate. No comparative study of these contemporary modalities exists. Methods: Charts for patients with low-risk prostate cancer by NCCN criteria treated 1999-2012 were reviewed. For IGRT, the clinical target volume (CTV) included the prostate and proximal seminal vesicles. A CT-based, off-line adaptive treatment plan was made with a patient-specific confidence-limited planning target volume (cl-PTV) based on the planning plus four additional daily CT scans. Overall survival (OS) was calculated by the Kaplan-Meier method (log-rank test), with Cox regression for uni- and multi-variate analysis. Cumulative incidence (Gray’s test), with competing risks analysis (Fine and Gray) were used for biochemical control (BC) and freedom from local recurrence (FFLR). Results: There were 598 IGRT and 399 HDR patients (see Table), with a median follow-up of 6.1 and 3.6 years, respectively (p&lt;0.001). The median prescribed IGRT dose was 75.6 Gy (range 73.8-79.2). HDR doses were 24 Gy (n=126) or 27 Gy (n=151) in 2 fractions, or 36 Gy (n=3) or 38 Gy (n=335) in 4 fractions. Five- and 10-year BC was 99% and 94% for IGRT and 98% and 95% for HDR (p=0.77); FFLR was 100% and 99% for both (p=0.89); and OS was 95% and 75% for IGRT and 97% and 85% for HDR (p=0.04). On multivariate analysis, predictors (p&lt;0.10) for OS were age (p&lt;0.001) and PNI (p=0.04); for LR, PPC (p=0.01); and for BC, a trend for PSA (p=0.08). Treatment type was not a predictor of OS, BC or FFLR (p&gt;0.5). Conclusions: Both dose- escalated IGRT and HDR monotherapy yield similarly excellent outcomes for low-risk prostate cancer. Our experience supports the continued use of brachytherapy as monotherapy in low-risk prostate cancer. [Table: see text]

Three-dimensional Summation of Rectal Doses During Combined Seed Implant Brachytherapy and External Beam Radiation Therapy for Prostate Cancer

Rectal bleeding is more common after combined I-125 seed implant brachytherapy (BRT) and external beam radiation therapy (EBRT) than after BRT monotherapy. To determine the total rectal dose constraints for this multimodal therapy, the dose matrix of both radiotherapies was summed to plot a dose-volume histogram (DVH) for comparing rectal bleeding.

Comparison of PSA Kinetics Between Hypofractionated Stereotactic Body Radiation Therapy, Conventionally Fractionated External Beam Radiation, and High-dose-rate Brachytherapy

Clinical outcomes in prostate cancer patients have been linked to a lower PSA nadir and a more rapid decline in PSA after treatment (e.g. PSA kinetics). Furthermore, dose escalation with external beam radiation therapy (EBRT) has been associated with improved clinical outcomes. The evidence for a low α/β ratio for prostate cancer, and the desire to shorten treatment, has led to the use of hypofractionated radiation therapy to deliver a higher bioequivalent dose. At UCSF low and low-intermediate risk prostate cancer patients are treated definitively with hypofractionated stereotactic body radiation therapy (SBRT) monotherapy, with a dose and fractionation based on HDR brachytherapy monotherapy. We undertook this retrospective study to compare the biological response (kinetics of PSA decline and PSA nadir) after definitive monotherapy with SBRT compared with EBRT and HDR. We hypothesize that the hypofractionated treatment regimen should result in a more rapid PSA decline than conventionally fractionated EBRT and be equivalent to HDR. One hundred eighty-two patients were retrospectively identified with low and intermediate risk defined as Gleason G3+3 PSA < 20 or G3+4 PSA < 15 treated with definitive external beam monotherapy to the prostate only, with at least 3 serial PSAs and 1 year of follow up. Patients were also excluded if they failed therapy by the ASTRO Phoenix definition. Twenty-seven patients treated with SBRT to the prostate with 38 Gy in 4 daily fractions met the same criteria, as did 13 patients treated with HDR, treated with either 950 cGy x 4 fractions or 1050 cGy x 3 fractions. PSA slope is the change in PSA versus time. Median follow-up for the SBRT, EBRT, and HDR cohorts were 37, 62 and 19 months, respectively. The median PSA nadirs for SBRT, EBRT and HDR were 0.26, 0.66 and 0.20 ng/mL respectively, and the median PSA slopes were -.057, -0.003, and -0.054 ng/mL/month, respectively. The rate of PSA decline was significantly slower with EBRT compared with either SBRT or HDR (p < 0.001). The distributions of PSA nadir values statistically differed between all pairs of treatments, although the time to observed nadir was significantly longer with HDR. The hypofractionated regimen delivered by SBRT resulted in a rapid decline in PSA similar to HDR, but faster than EBRT, reflecting the similarity in dose and fractionation of SBRT and HDR. The short follow up for the HDR cohort, and the long median time to PSA nadir (74 months), does not allow comparison of the HDR nadir. The exclusion of failures and long follow up are reflected in the low PSA nadir for EBRT. SBRT does result in similar kinetics to HDR treatment, and is approaching PSA nadirs of HDR treatments in historical series, illustrating its biological equivalence to HDR.

Dose-escalated Adaptive Image Guided Radiation Therapy Versus High-dose-rate Brachytherapy Monotherapy for Gleason 7 Intermediate-Risk Prostate Cancer: A Matched Pair Analysis

Dose-escalated Adaptive Image Guided Radiation Therapy Versus High-dose-rate Brachytherapy Monotherapy for Gleason 7 Intermediate-Risk Prostate Cancer: A Matched Pair Analysis

Gracilis muscle interposition with primary rectal without urethral repair for moderate sized rectourethral fistula caused by brachytherapy for prostate cancer: a case report

IntroductionThere is a 0.16% chance of a rectourethral fistula after prostate brachytherapy monotherapy using Palladium-103 or Iodine-125 implants. We present an unusual case report of a rectourethral fistula following brachyradiotherapy monotherapy for prostate adenocarcinoma. It was also associated with unusual management of the fistula.Case presentationA 58-year-old Caucasian man underwent brachyradiotherapy monotherapy as definitive treatment for verified intracapsular prostate adenocarcinoma receiving 56 Iodine-125 implants using a transrectal ultrasound-guided technique. The patient started to complain of severe perineal pain and mild rectal bleeding 15Â months after brachyradiotherapy. A biopsy of mucosa of his anterior rectal wall was performed. A moderate sized rectourethral fistula was confirmed 23Â months after implantation of Iodine-125 seeds. Laparoscopic sigmoidostomy and suprapubic cystostomy were then performed. Long-term cortisone applications in combination with 30 sessions of hyperbaric oxygen therapy, and antibacterial therapies were initiated due to necrotic infection. A gracilis muscle interposition to create a partition between the patient's rectum and urethra in conjunction with primary rectal repair but without urethral repair were performed 6 months later. The 3cm rectal defect was repaired via a 3cm-long horizontal perineal incision. The 1.5cm urethral defect just below the prostate was not repaired. The patient underwent an optic internal urethrotomy 3Â months later for a 1.5cm-long urethral stricture. Several planned preventive urethral buginages were performed to avoid urethral stricture recurrence. At 12Â months postoperatively, there were no signs of a fistula and cancer recurrence. He now has a normal voiding and anal continence.ConclusionSevere rectal pain, bleeding, and local anterior necrotic proctitis are predictors of a rectourethral fistula. Urinary and fecal diversion is the first-step operation. Gracilis muscle interposition in conjunction with primary rectal repair but without urethral reconstruction is one of the reconstructive surgery options for moderate 2cm to 3cm rectourethral fistulas. Internal urethrotomy is a procedure for postoperative urethral strictures of 1.5cm in length.

Endorectal magnetic resonance imaging for predicting pathologic T3 disease in Gleason score 7 prostate cancer: Implications for prostate brachytherapy

To determine the ability of endorectal magnetic resonance imaging (erMRI) and other pretreatment factors to predict the presence and extent of extraprostatic extension (EPE) in men with Gleason score (GS) 7 prostate cancer. We included patients with clinical stage T1c-T2c, GS=7 (3+4 or 4+3), and prostate-specific antigen (PSA) <10ng/mL who underwent pre-prostatectomy erMRI. We compared pathologic EPE findings with pretreatment factors. One hundred seventy-one men were eligible for inclusion. Pretreatment characteristics were: median age=60 years (42-76); median PSA 4.9ng/mL (0.4-9.9); GS 3+4=61%; T1c=51%; T2a=25%; T2b=21%; T2c=3%; ≥50% positive cores=46%; EPE-positive (EPE+) erMRI=28%. Thirty-three percent had pathologic EPE. Increasing T-stage (p<0.0001) and EPE+ erMRI (p<0.0001) were significant predictors of pathologic EPE, whereas GS (4+3 vs. 3+4) (p=0.14), percentage of positive core biopsies (p=0.15), and pretreatment PSA (p=0.41) were not. Median EPE distance was 1.75mm (range, <1-15mm). The rates of EPE >5mm and EPE >3mm were 11% and 15%, respectively. The odds ratios for erMRI detection of any EPE and of EPE >5mm were 3.06 and 3.75, respectively. T-stage and EPE+ erMRI predict pathologic EPE in men with GS 7 prostate cancer. The ability of erMRI to detect EPE increases with increasing EPE distance. These findings may be useful in patient selection for prostate brachytherapy monotherapy.

Preoperative treatment planning with intraoperative optimization can achieve consistent high-quality implants in prostate brachytherapy

Advances in brachytherapy treatment planning systems have allowed the opportunity for brachytherapy to be planned intraoperatively as well as preoperatively. The relative advantages and disadvantages of each approach have been the subject of extensive debate, and some contend that the intraoperative approach is vital to the delivery of optimal therapy. The purpose of this study was to determine whether high-quality permanent prostate implants can be achieved consistently using a preoperative planning approach that allows for, but does not necessitate, intraoperative optimization. To achieve this purpose, we reviewed the records of 100 men with intermediate-risk prostate cancer who had been prospectively treated with brachytherapy monotherapy between 2006 and 2009 at our institution. All patients were treated with iodine-125 stranded seeds; the planned target dose was 145 Gy. Only 8 patients required adjustments to the plan on the basis of intraoperative findings. Consistency and quality were assessed by calculating the correlation coefficient between the planned and implanted amounts of radioactivity and by examining the mean values of the dosimetric parameters obtained on preoperative and 30 days postoperative treatment planning. The amount of radioactivity implanted was essentially identical to that planned (mean planned radioactivity, 41.27 U vs. mean delivered radioactivity, 41.36 U; R2 = 0.99). The mean planned and day 30 prostate V100 values were 99.9% and 98.6%, respectively. The mean planned and day 30 prostate D90 values were 186.3 and 185.1 Gy, respectively. Consistent, high-quality prostate brachytherapy treatment plans can be achieved using a preoperative planning approach, mostly without the need for intraoperative optimization. Good quality assurance measures during simulation, treatment planning, implantation, and postimplant evaluation are paramount for achieving a high level of quality and consistency.

Biochemical outcomes for patients with intermediate-risk, organ-confined prostate cancer treated with I-125 interstitial brachytherapy monotherapy.

192 Background: Treatment with low dose rate brachytherapy (LDR-BT) monotherapy is well established for low risk prostate cancer. The routine use of LDR-BT in intermediate risk (IR) is more controversial and is often combined with additional external beam radiotherapy (EBXRT). We report the biochemical outcome of a large cohort of patients with IR disease treated with LDR-BT monotherapy. Methods: A multi-institutional prospective database identified 615 patients with IR prostate cancer treated with I-125 interstitial BT between 2003–2007. IR was defined using Memorial Sloan-Kettering Cancer Centre (MSKCC) definition of either T2b, or Gleason score (GS) 7 or raised initial PSA (iPSA) 10.1-20ng/ml. Patients receiving additional EBXRT were excluded. Biochemical failure was defined by both ASTRO (3 rises past nadir) and Phoenix criteria (nadir plus 2). Kaplan-Meier methods were used to estimate biochemical no evidence of disease rates (bNED) and univariate analyses used to identify potential prognostic factors. Results: The median age was 64 years (range 49–82). Forty-three patients had stage T2b, 180 had iPSA 10.1-20 and 392 had GS 7 disease. Only 108 received androgen deprivation therapy (ADT) prior to implant. Median follow up was 5.0 years. The 5-year bNED rates (95% confidence interval) by ASTRO are 85.5% (82.0–88.3%) and for Phoenix 83.7% (80.0–86.7%). Use of ADT, GS 3+4 versus 4+3, and dosimetric indices were not significant prognostic variables. When stratified by risk factor (T2b, GS7 or raised iPSA) raised iPSA correlated to poorer outcome only by Phoenix criteria (by Phoenix p=0.001, by ASTRO p=0.311). Conclusions: We have demonstrated good biochemical control for IR patients treated with LDR-BT alone. No additional benefit was seen with the use of ADT. We believe LDR-BT alone is an effective treatment option in selected IR prostate cancer patients with comparable outcome to other treatment modalities such as surgery or EBXRT.

The Number of High-Risk Factors and the Risk of Prostate Cancer–Specific Mortality After Brachytherapy: Implications for Treatment Selection

To determine whether an increasing number of high-risk factors is associated with higher prostate cancer-specific mortality (PCSM) among men treated with brachytherapy (BT)-based treatment, and whether supplemental therapy has an impact on this risk. We analyzed the cases of 2234 men with localized prostate cancer treated between 1991 and 2007 with low-dose rate BT monotherapy (n = 457) or BT with supplemental external-beam radiotherapy (EBRT, n = 229), androgen suppression therapy (AST, n = 424), or both (n = 1124). All men had at least one high-risk factor (prostate-specific antigen >20 ng/mL, biopsy Gleason score 8-10, or clinical stage ≥T2c). Competing-risks multivariable regressions were performed to determine whether the presence of at least two high-risk factors was associated with an increased risk of PCSM, with adjustment for age, comorbidity, and the type of supplemental treatment. The median follow-up time was 4.3 years. The number of men with at least two high-risk factors was highest in the group treated with BT, EBRT, and AST (21%), followed by BT plus EBRT or AST (13%), and BT alone (8%) (p(trend) < 0.001). The adjusted hazard ratio (AHR) for PCSM for those with at least two high-risk factors (as compared with one) was 4.8(95% confidence interval [CI], 2.8-8.0; p < 0.001). The use of both supplemental EBRTand AST was associated with a decreased risk of PCSM (AHR 0.5; 95% CI, 0.2-0.9; p = 0.03) compared with BT alone. When the high-risk factors were analyzed separately, Gleason score 8-10 was most significantly associated with increased PCSM (AHR 6.2; 95% CI, 3.5-11.2; p < 0.001). Men with high-risk prostate adenocarcinoma treated with BT have decreased PCSM if they receive trimodailty therapy that includes EBRT and AST. This benefit is likely most important in men with multiple determinants of high risk.

Clinical analysis of permanent 125I prostate brachytherapy monotherapy for early prostate cancer ( report of 18 cases)

Objective To evaluate the clinical efficacy of permanent 125I prostate brachytherapy monotherapy in patients with early prostate cancer. Methods A total of 18 patients with prostate cancer was diagnosed by prostate biopsy,with Gleason score 5 - 6,average PSA 5.09 ng/ml (range,0.38 -8.73 ),and clinical stage T1c - T2a.All patients underwent 3-dimensional conformal brachytherapy with transperineal ultrasound-guide 125I seeds prostate implantation. Results None of the patients had any adverse events during the operation processes.The operation time was from 37 to 52 minutes and postoperative hospitalization time was from 3 to 4 days.The mean number of implanted 125I seeds was 54.All patients were followed up for 3 to 57 months with a mean of 15 months,while one patient was lost during followingup.The survival rate of PSA progression free was 100％ (17/17).The PSA was under 0.2 ng/ml for a long time in the 7 cases who had been followed-up for more than 18 months.The PSA did not show any rising trend in all 17 cases.No severe complications occurred in all cases. Conclusions Brachytherapy monotherapy with 125I seeds implantation is safe and effective for patients with early prostate cancer. Key words: Prostatic neoplasms; Carcinoma; 125I brachytherapy

Acute and Chronic Toxicity Profiles Associated with Three High-Dose-Rate Interstitial Brachytherapy Monotherapy Fractionation Schedules for Localized Prostate Cancer

To compare the acute and chronic toxicity profiles associated with three high-dose-rate interstitial brachytherapy (HDR) monotherapy fractionation schedules: 38 Gy in 4 fractions (38/4), 24 Gy in 2 fractions (24/2), and 27 Gy in 2 fractions (27/2). 482 patients with low-risk (69%) or intermediate-risk (31%) prostate cancer were treated with Ir-192 following ultrasound-guided, percutaneous implantation of afterloading catheters. Gland volumes and pre-treatment AUA scores were similar among groups. 317 patients received 38/4 (interfraction period: 6 h or 18 h); 72 received 24/2 (interfraction period: 6 h or 14 d); 93 received 27/2 (interfraction period: 6 h or 14 d). Chi-square, t-test, ROC, and univariate analyses were conducted to compare patient characteristics, clinical outcomes, and maximal acute (<6 m following treatment) and chronic (>6 m following treatment) toxicities. Patients were treated in an HIC approved sequential dose schedule protocol with the same eligibility criteria. Clinical outcomes were similar among groups, with 3-y actuarial rates of 91% (biochemical failure-free survival), 99% (overall survival), and 100% (cause-specific survival). Acute gastrointestinal (GI) toxicities (diarrhea, bleeding, proctitis, and pain/tenesmus) were similar among groups; no grade 3 or higher toxicities were reported. Patients receiving 38/4 experienced the highest rate of acute grade 1/2 dysuria (27%), urinary retention (22%), and incontinence (6%) (p = 0.04, 0.04, 0.01). Other acute genitourinary (GU) toxicity rates were similar among all patients, including grade 3 urinary frequency/urgency (2%) and grade 3 urinary retention (<1%). Patients receiving 38/4, 25/2, and 27/2 experienced dissimilar rates of chronic grade 1/2 diarrhea (3%, 11%, 7%; p = 0.02) and rectal bleeding (7%, 4%, 0%; p = 0.02). No grade 3 or higher chronic GI toxicity was reported in any group. Chronic GU toxicity was similar among groups, with <1% of all patients experiencing grade 3 dysuria, frequency/urgency, retention, incontinence, or hematuria. Nine patients (2%) developed a urethral stricture requiring surgical dilation. Patients receiving pre-treatment hormone therapy (HT) experienced higher acute GI and GU toxicities (20% and 70%) than patients not receiving HT (10% and 53%)(p = 0.03 and 0.02). Gland volume did not predict acute or chronic toxicity. The toxicity and preliminary clinical outcomes associated with 38/4, 24/2, and 27/2 are comparable. These data suggest that accelerated, hypofractionated HDR constitutes a well tolerated, convenient, and effective treatment modality. Additional follow-up to characterize long-term outcomes is warranted.

Radiotherapy of prostate cancer

Radiotherapy is used for all stages of prostate cancer from early localised disease to locally advanced as well as metastatic stages. The method of radiotherapy used is dependent on the stage of the disease and is guided by the application of prognostic factors or disease groupings such as the NCCN classification [1,2]. In general, localised disease can be treated by either brachytherapy or external beam radiotherapy (EBRT), with EBRT being used for more advanced disease stages. Historically. in men with locally advanced prostate cancer, either expectant therapy or androgen deprivation therapy (ADT) alone have been used to manage or treat these cases. However recent randomised trials that compared the addition of radiotherapy to ADT versus ADT alone have reported an overall survival advantage for combination therapy [3,4]. More recently, the combination of both brachytherapy and EBRT or high-dose rate brachytherapy monotherapy are being used to treat intermediate to advanced stages. For metastatic disease, both EBRT and isotope therapy have been used successfully to ameliorate and control symptomatic disease. Over the past decades, there have been substantial technological developments in radical radiotherapy with shaping of the treatment beams for conformal radiotherapy (CRT) and the ability to vary dose intensities within treatment fields for intensity-modulated radiotherapy (IMRT) [5]. In addition, multi-modality imaging, particularly with magnetic resonance imaging (MRI), functional MR such as spectroscopy and positron emission tomography (PET) has aided target volume delineation to ensure adequate coverage of disease and an opportunity to retarget biological radioresistant disease [6]. The use of CRT has been shown in a randomised trial to significantly reduce the incidence of clinically relevant rectal proctitis and bleeding (RTOG Grade 2) for the CFRT arm compared with conventional radiotherapy (5% vs. 15% respectively, P = 0.01) without any loss of PSA control [7] and established CFRT as the minimum standard for radical therapy. Subsequently, both CRT and IMRT have allowed the dose to be increased whilst respecting dose tolerances of the adjacent organ-at-risk (OAR), especially the rectum being the major dose-limiting structure. A dose–response relationship has been demonstrated by several randomised trials. The results of these dose escalation studies for non-metastatic prostate cancer using mainly CRT are listed in Table 1 [8–14]. More recently a meta-analysis [15] confirmed that an increase in radiotherapy dose from 70Gy to 80Gy results in an increase in biochemical prostate specific antigen (bPSA) control rates by approximately 19% in patients with intermediate to high-risk prostate cancer [15]. Despite optimising CFRT techniques [16–18], the degree of dose escalation is limited as CRT is unable to spare the rectum if it lies within the concavity of the planning target volume [19]. This physical limitation will technically limit the degree of dose escalation possible with CRT. This is clearly demonstrated by the toxicity noted in the dose escalation trials outlined in Table 1, with the incidence of late GI toxicity (RTOG grade 2) being doubled by dose escalation to 74−78Gy. Whilst most of these randomised trials have used CRT, the Massachusetts General Hospital (MGH) study used protons to deliver the escalated dose [11]. Although proton therapy may potentially provide a technically improved dose distribution through manipulation of the Bragg peak dose deposition, the toxicity reported in the escalation arm was similar to that of other studies. It was expected that the ability to vary the dose fluence over treatment fields using IMRT can substantially improve dose conformity and OAR avoidance. In the large prospective non-randomised series from the Memorial Sloan Kettering Cancer Centre, both acute and late toxicities were substantially reduced, even when escalating dose to 81Gy and 86.4Gy with late 3-year actuarial Grade 2 GI toxicity for this series of 772 cases being calculated at 4% [20]. A recent update with 10-year outcomes reported that the 10year likelihood of developing grade 2 and 3 late GI toxicity was 2% and 1% respectively [21].

The clinical impact of pathological review on selection the treatment modality for localized prostate cancer in candidates for brachytherapy monotherapy

To evaluate the impact of pathological review by pathologist with genitourinary expertise (PGU) on treatment modality of localized prostate cancer, we analyzed Gleason grade (GG) migration and the final treatment decision in a cohort of patients designated for permanent prostate brachytherapy (PPB). From February 2005 to July 2010, a total of 247 patients with localized prostate cancer diagnosed by local community hospitals were referred to our hospital for PPB monotheray. All pathologic slides of prostate biopsies were reviewed by a single PGU. Patients ultimately selected their treatment modality from our recommendations based on the review. Indication for PPB monotherapy was the NCCN classification of patients as good or intermediate risk. In addition, patient with Primary GG 4 was regarded as unadapted case. Six cases were reinterpreted as no cancer (2.4%). GG change occurred in 94 cases (38.1%) of which 77 (81.9%) were upgraded and 17 (18.1%) downgraded. Of the total 247 patients, 86 (34.8%) changed therapies and 30 (12.1%) did so based on the pathologic slide review. Pathological review of biopsy specimens is mandatory for the determination of treatment modality especially in candidates for monotherapy of permanent prostate brachytherapy.