Permanent prostate brachytherapy monotherapy with I-125 for low- and intermediate-risk prostate cancer: Outcomes in 974 patients

Purpose

To report outcomes of patients undergoing low-dose-rate (LDR) brachytherapy and investigate factors associated with biochemical failure and survival.

3-D Conformal HDR Brachytherapy as Monotherapy for Localized Prostate Cancer

PURPOSE: Pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose- rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning. PATIENTS AND METHODS: Between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) < or = 10 ng/ml, Gleason score < or = 7 and clinical stage < or = T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT((R)) was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (D(ref)) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D(90), D(10) urethra, and D(10) rectum. Acute toxicity was evaluated using the CTC (Common Toxicity Criteria) scales. RESULTS: Median D(90) was 106% of D(ref) (range: 93-115%), median D(10) urethra 159% of D(ref) (range: 127-192%), and median D(10) rectum 55% of D(ref) (range: 35-68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred. CONCLUSION: 3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.     

Combination conformal radiotherapy and radioimmunoguided transperineal Pd implantation for patients with intermediate and unfavorable risk prostate adenocarcinoma

PURPOSE: To report outcomes for prostate cancer patients treated with external beam radiation therapy (EBRT) and permanent prostate brachytherapy utilizing radioimmunoguided targeting of biological tumor volumes (BTVs). METHODS AND MATERIALS: Between February 1997 and October 2001, 66 patients with intermediate- to high-risk prostate cancer underwent EBRT and ProstaScint-guided transperineal brachytherapy. Thirty patients received neoadjuvant hormonal manipulation, while 36 patients did not. Median patient age was 66 years (range, 49-78 years). The median follow-up was 41 months (range, 24-78 months). No patients were lost to follow-up. Risk factors (RF) used for risk stratification included PSA >10 ng/ml (35 patients), Stage T2b or greater (22 patients), and Gleason score > or = 7 (55 patients). Results for biochemical disease free survival (bDFS) were reported using the ASTRO consensus definition for biochemical failure, PSA < or = 1.0 ng/mL or PSA< or = 0.5 ng/mL. Survival was estimated by the Kaplan-Meier method. RESULTS: Five-year overall survival was 93.1% and 5-year bDFS by the ASTRO definition was 89.3% with a median follow up of 41 months. Patients with intermediate- (1 RF) and high-risk (2-3 RF) prostate cancer exhibited 5-year ASTRO-defined bDFS of 100% and 81.9%, respectively. There was no significant difference in bDFS between the patients treated with or without hormone therapy (HT). The 5-year ASTRO-defined bDFS was 89.8% for the 30 patients treated with HT and 88.9% for the 36 patients who did not receive HT (p = 0.843). For the patients without HT the median PSA nadir was 0.11 ng/mL. The median time to nadir was 23 months (range, 6-66 months). CONCLUSIONS: With limited follow-up, the results of EBRT plus radioimmunoguided brachytherapy for intermediate- to high-risk prostate cancer appear favorable. The addition of HT did not appear to affect bDFS significantly, but interpretation is confounded by possible selection bias and the limited power of this study.     

Australian prostate-specific antigen outcome and toxicity following radiation therapy for localized prostate cancer

The objective of the present study was to examine prostate-specific antigen relapse free survival (PSA-RFS) and morbidity following 'conventional' radical radiation therapy for prostate cancer in two Australian regional treatment services. Four hundred and eighty men with clinically localized prostate cancer were treated between 1993 and 1997 at Liverpool and Westmead Hospitals using a standardized 4-field, CT-planned radiotherapy technique. Principal endpoints were PSA-RFS (American Society for Therapeutic Radiology and Oncology guidelines definition) and late rectal and urinary morbidity (Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria). The median follow up of patients from the end of RT was 55 months. Prospectively, they were divided into three prognostic categories: (i) high risk T3 or 4 and/or PSA > 20 ng/mL and/or Gleason score 8-10 (40% of cohort); (ii) intermediate risk T1 or 2 and PSA 10-20 ng/mL and/or Gleason score 7 (33% of cohort); and (iii) low risk T1 or 2 and PSA < 10 ng/mL and Gleason score < 6 (27% of cohort). The 5-year actuarial PSA-RFS was 53% for the whole patient group. The 4-year rates were 32, 56 and 75% for high, intermediate and low risk groups, respectively. On multivariate analysis, T-stage, Gleason score, pre-RT-PSA were strong independent predictors of PSA-defined outcome. Late (grade 2) rectal and urinary morbidity occurred at some point in time in the post-RT period in 8.0 and 5.8% of patients, respectively. These results confirm that low Gleason score, low T stage, presenting PSA < 10 ng/mL and nadir < 1 ng/mL remain the strongest predictors of a good outcome. Long-term toxicity was very acceptable. However, further improvement in outcome is desirable, and with the adoption of new technology allowing escalation of radiotherapy doses such an expectation might be achieved.     

103Pd brachytherapy versus radical prostatectomy in patients with clinically localized prostate cancer: a 12-year experience from a single group practice

PURPOSE: In an effort to shed light on the continuing debate over the best treatment options for patients with localized prostate cancer, we present a retrospective review of patients from a single group community urology practice. METHODS AND MATERIALS: Data from 1707 patients were reviewed. These patients, with T1 or T2 adenocarcinoma of the prostate, were treated from 1992 to 2004 with either brachytherapy or radical retropubic prostatectomy (RRPP); 81% were aged over 65 years. Patients were classified into risk groups based on initial prostate-specific antigen (PSA) and Gleason score. Time to PSA-indicated recurrence was used as the measure of disease control and cure. RESULTS: Time to PSA-indicated recurrence was used as a measure of efficacy. Brachytherapy with 103Pd exclusively and RRPP were found to provide equivalent control (<0.4 ng/mL for prostatectomy and <3 successive rises in PSA as defined by the American Society for Therapeutic Radiology and Oncology [ASTRO]) in low-risk groups (89% seeds vs. 94% RRPP). In intermediate (89% seeds vs. 58% RRPP) and high-risk (88% seeds vs. 43% RRPP) groups, brachytherapy patients had better control rates. The addition of external radiation, with or without luteinizing hormone-releasing hormone therapy, improved biochemical control rates in intermediate and high-risk brachytherapy groups. CONCLUSION: The results failed to show any superiority of prostatectomy over brachytherapy with 103Pd (TheraSeed; Theragenics Corp., Buford, GA) regarding time until relapse as indicated by PSA level increase (>0.4 ng/mL for prostatectomy and >3 successive rises in PSA as defined by ASTRO). We recently reviewed our techniques and improved equipment from 1995 to present and found major gains with both brachytherapy and surgery. Low risk brachytherapy resulted in 99% freedom from PSA failure while surgery showed results of 97%. Brachytherapy and prostatectomy should be offered without bias to all men with stage T1 and T2 organ-confined prostate cancer.     

Four-year outcomes of hypofractionated high-dose-rate prostate brachytherapy and external beam radiotherapy

PurposeHigh-dose-rate (HDR) brachytherapy boost in prostate cancer allows dose escalation and delivery of higher biologically effective dose (BED). We evaluated the outcomes of intensity-modulated radiation therapy (IMRT) and HDR boost in a community setting.Methods and MaterialsBetween July 2003 and April 2008, 148 patients with prostate cancer were treated at Cancer Center of Irvine using two transperineal implants performed 1 week apart (22 Gy delivered in four fractions divided between two insertions and delivered twice daily), followed by IMRT (50.4 Gy). Hormonal therapy was given for 1 year to all patients with Gleason score of 8 or higher.ResultsPatient characteristics are as follows: median age at treatment, 71 years; American Joint Committee on Cancer Group IIB, 53%; Gleason score of 7, 41%; and Gleason score of 8 or higher, 14%. Median followup was 49 months, and median prostate-specific antigen (PSA) nadir was 0.15 ng/mL. The 4-year actuarial biochemical disease-free survival (bDFS) was 96.8/81% by Phoenix/PSA lower than 0.5 ng/mL criteria. According to National Comprehensive Cancer Center Clinical Practice Guidelines–defined recurrence risk groups, 4-year bDFS for low risk was 100/92.9%, intermediate risk was 100/86.7%, and high risk was 94/75.4% by Phoenix/PSA lower than 0.5 ng/mL criteria. No statistically significant difference in bDFS was detected by either failure criteria based on risk group, lymph node risk, or initial PSA. Treatment was well tolerated. Subacute/late genitourinary and gastrointestinal toxicities were limited to 10% and 5%, respectively of all patients.ConclusionsProstate IMRT plus HDR brachytherapy boost was well tolerated with appropriate PSA response and bDFS at 4 years, demonstrated in a community setting. This treatment schema provides a high BED, comparable with hypofractionated prostate regimens previously reported in the literature. Higher BED delivery should be explored in further dose escalation studies.     

Single-Institution Results of Primary External-Beam Radiation for the Treatment of T1–T3 Prostate Cancer

PURPOSE: To evaluate survival and toxicity rates after primary external-beam radiation for the treatment of prostate cancer. PATIENTS AND METHODS: Data of 306 patients treated with conformal external beam radiation between 1996 and 2001 were collected. These were evaluated in terms of overall, cause-specific and disease-free survival as well as toxicity. Furthermore, an investigation of possible risk factors was performed. RESULTS: Toxicity rates compared favorably with other series with 5.2% RTOG 1-2 and no RTOG > 2 long-term side effects. Actuarial 5-year overall survival rates with and without biochemical failure were 77% versus 78%, cancer-specific survival was 85.41% versus 100%, and disease-free survival was 71.54%, respectively. Potential risk factors for cancer-related death were biochemical failure, initial serum prostate-specific antigen (PSA) and Gleason score. CONCLUSION: Toxicity rates were found to be surprisingly low compared to other series, which is likely due to low daily dose and consistent MR-based treatment planning. In terms of survival, no significant differences to other trials could be observed. Initial PSA and Gleason score were significant predictors for treatment outcome in terms of survival.     

Efficacy of brachytherapy for prostate cancer in African Americans compared with Caucasians

PURPOSE: To compare the biochemical response to prostate brachytherapy between African Americans and Caucasians in a consecutive series of patients treated at a single institution. METHODS AND MATERIALS: Between July 1995 and October 2001, 173 patients were treated with permanent (125)I seed implantation alone for presumed localized adenocarcinoma of the prostate. Twelve patients were African American and their biochemical response to treatment was compared with the 161 Caucasian patients. The patients were evaluated for biochemical recurrence according to the ASTRO consensus statement and for achieving and maintaining PSA nadirs of < or = 1.0, < or = 0.5, and < or = 0.2. Median pretreatment PSA level was 8 for the African American group and 6 for the Caucasian group. Median Gleason score for each group was 6 and no patients had palpable extraprostatic disease at the time of treatment. RESULTS: None of the African American patients have experienced biochemical recurrence compared with 7.5% of the Caucasian patients (p=0.34). The percentage of African American patients achieving and maintaining a PSA level of < or = 1.0 was 83% compared with 89% for the Caucasian patients (p=0.61). PSA nadir of < or = 0.5 was achieved in 75% of the African American patients and 81% of the Caucasian patients (p=0.52) and 50% of the African American patients experienced PSA levels of < or = 0.2 compared with 59% of the Caucasian patients (p=0.88). CONCLUSION: African American patients with prostate cancer have in general been reported to have worse prognosis compared with Caucasians. This series suggests similar outcome between African American and Caucasian patients treated with brachytherapy for prostate cancer.     

Combined modality treatment with high-dose-rate brachytherapy boost for locally advanced prostate cancer

PURPOSE: This is a retrospective review of our experience using high-dose-rate (HDR) brachytherapy boost for prostate cancer. METHODS AND MATERIALS: During the study period, we recommended external beam radiotherapy (45 Gy) and HDR boost (18 Gy in three fractions) combined with hormonal therapy (HT) for 2 months before and during radiotherapy to patients with at least one of the following risk features: pretreatment prostate-specific antigen>10, Gleason score (GS)>or=7, and clinical T3 disease. Additional HT for 2 years after radiotherapy was recommended for patients with GS>7. To patients whose risk of positive nodes exceeded 15%, we recommended whole pelvic radiotherapy. We administered HDR via single implant, and all fractions were given within 24h. RESULTS: This report is based on our initial 64 patients treated with HDR boost. The median follow-up was 50 months (range 25-68 months). The 4-year estimates of overall and disease-free survival were 98% and 92%, respectively. One patient experienced late grade 4 gastrointestinal toxicity. CONCLUSIONS: HDR brachytherapy is an effective means of delivering conformal prostate radiotherapy, and may be used with whole pelvic radiotherapy and HT.     

Analysis of Competing Risk Parameters in Irradiated Prostate Cancer Patients

PURPOSE: Retrospective competing risk analysis of prognostic factors in definitive-irradiated prostate cancer patients. PATIENTS AND METHODS: Data of 652 patients were analyzed according to three age subgroups (< 65, 65 < or = 75, > 75 years; Table 1). Pre-RT PSA values (median 13.4 ng/ml) were available for 340 patients. Adjuvant hormone therapy (n = 261) consisted either of orchiectomy (n = 151) or LHRH agonist with/without antiandrogen therapy or, in the early years, diethylstilbestrol. Neoadjuvant hormone therapy (n = 31) using LHRH agonists was given 6 months before and during radiotherapy. RESULTS: Biochemical failure was observed in 69/340 patients, 5 years after biochemical failure, 64.9% of them also had failed clinically. The cumulative incidence of local failure (LF) and distant metastases (DM) was 9.4% and 37.2%, respectively; LF and DM at the same time were seen in 18.2%. On multivariate analysis (Tables 2 and 3), advanced stage (relative risk [RR] 4.54), pre-RT PSA > 20 ng/ml (RR 2.79) and poorly differentiated tumors (RR 2.96) were significant predictors of biochemical failure. Advanced stage increased the risk of LF (RR 2.18), DM (RR 3.66), and prostate cancer death (PCD; RR 4.30). Hormone therapy decreased the risk of biochemical failure (RR 0.67), DM (RR 0.59), and PCD (RR 0.60) without reaching statistical significance. Median follow-up was 7.6 years. CONCLUSION: Risk of biochemical failure was predicted by pre-RT PSA, stage, and grade; in patients with biochemical failure, the cumulative incidence of death from intercurrent diseases and PCD was 25.0% and 29.2% after 5 years, respectively. The risk of DM and PCD was predicted by stage and grade. Higher age (> 75 years) decreased the relative risk of LF, DM, and PCD significantly.     

Long-term outcomes of prostate cancer patients with Gleason pattern 5 treated with combined brachytherapy and external beam radiotherapy

PurposeRecent reports have suggested relatively poor prognosis for prostate cancer patients with Gleason pattern 5 treated with dose-escalated external beam radiotherapy (XRT) and androgen deprivation therapy (ADT). We present the largest series of men with high-risk, Gleason pattern 5 prostate cancer treated with permanent interstitial brachytherapy and XRT.Methods and MaterialsBetween April 1995 and December 2008, 329 consecutive patients with National Comprehensive Cancer Network high-risk disease were treated with permanent interstitial brachytherapy. Most received XRT and ADT. Median followup was 7.2 years. The cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters.ResultsAt 10 years, biochemical progression-free survival, cause-specific survival (CSS), and overall survival for the group of high-risk patients as a whole was 91.1%, 95.5%, and 72.5%, respectively. There was no difference in biochemical progression-free survival between men with and without Gleason pattern 5 (89.7% vs. 91.8%; p = 0.56). However, men with Gleason pattern 5 had lower prostate cancer CSS (90.3% vs. 98.1%; p = 0.011). There was no difference in overall survival comparing men with and without Gleason pattern 5 disease (67.7% vs. 75.4%; p = 0.14).ConclusionsMen with high-risk, Gleason pattern 5 histology treated with brachytherapy and XRT have excellent long-term outcomes, which compare favorably to dose-escalated XRT/ADT series without brachytherapy. Nonetheless, Gleason pattern 5 results in lower CSS than high-risk disease without Gleason pattern 5.     

Gleason score 7 prostate cancer treated with interstitial brachytherapy with or without supplemental external beam radiation and androgen deprivation therapy: Is the primary pattern on needle biopsy prognostic?

PurposeTo evaluate the effect of primary Gleason pattern on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) in Gleason 7 prostate cancer patients treated with low-dose-rate (LDR) interstitial brachytherapy with or without supplemental external beam radiation therapy and androgen deprivation therapy.Methods and MaterialsWe retrospectively reviewed the medical records of 932 consecutive patients with biopsy-confirmed Gleason 7 prostate cancer who received LDR interstitial brachytherapy as a component of their definitive treatment regimen. Treatment outcomes were compared between patients with primary Gleason pattern 3 and 4.ResultsWith a median followup of 7.4 years, the 10- and 14-year bPFS, CSS, and OS for the entire Gleason 7 study group were 95.7/95.7%, 98.6/98.6% and 77.2/64.3%, respectively. When biochemical control was evaluated as a function of primary Gleason pattern, the primary pattern 3 had a statistically higher 10- and 14-year bPFS (97.8/97.8% vs. 93.1/93.1%, p = 0.006). The Gleason pattern 3 patients also trended toward a higher 10- and 14-year CSS (99.3/99.3% vs. 96.9/96.9%, p = 0.058). OS was not statistically different between the two Gleason 7 cohorts.ConclusionsGleason 7 prostate cancer patients treated with LDR interstitial brachytherapy have an excellent long-term outcome. There was a small but statistically significant advantage in bPFS and a trend toward improved CSS in patients with a primary Gleason pattern of 3.     

Preliminary toxicity and prostate-specific antigen response of a Phase I/II trial of neoadjuvant hormonal therapy, 103Pd brachytherapy, and three-dimensional conformal external beam irradiation in the treatment of locally advanced prostate cancer

PURPOSE: Standard therapies for locally advanced prostate cancer have resulted in suboptimal disease control rates. A Phase I/II trial was designed for patients with positive seminal vesicle biopsies, prostate-specific antigen (PSA) >15 ng/ml, Gleason score > or =8 or clinical classification T2c-T3 to improve local control and to test the tolerance of the prostate to high-dose radiation by using neoadjuvant hormonal therapy, 103Pd brachytherapy, and conformal three-dimensional external beam radiation therapy (EBRT). This article outlines treatment-related morbidity and PSA response to this regimen and analyzes the effect of escalating doses of brachytherapy. METHODS AND MATERIALS: Forth-three patients with T1c-T3 prostate cancer were enrolled in a Phase I/II trial from March 1994 through September 1997. Follow-up ranged from 12 to 64 months (median, 32 months). Pretreatment PSA ranged from 2.1 to 202 ng/ml (median, 16 ng/ml). Seventy-seven percent (33 of 43) of patients had high-grade tumors (score > or =7). Seventy-four percent (32 of 43) had stage > or =T2c. A total of 21 (49%) patients had positive seminal vesicle biopsies. Treatment consisted of hormonal therapy for 3 months with leuprolide and flutamide followed by a 103Pd implant and, 2 months later, 59.4 Gy of three-dimensional EBRT. Hormonal therapy was continued for 9 months. The planned 103Pd dose was escalated from 57 Gy (13 patients) to 77 Gy (13 patients) to 86 Gy (17 patients). RESULTS: The actuarial freedom from PSA failure (PSA>0.5 ng/ml) at 4 years was 74%. There were no significant differences found when analyzing patients by presenting PSA or seminal vesicle status. There was a trend toward improved outcome with higher doses delivered to the prostate via the implant. Patients receiving doses > or =65 Gy (31 patients) had a freedom from PSA failure rate at 4 years of 89.5%, compared with 52.5% for those receiving doses <65 Gy (10 patients; p=0.08). The last PSA values for those patients free from PSA failure were < or =0.1 ng/ml in 25 (69%), >0.1-0.2 ng/ml in 5 (14%), and >0.2-0.5 ng/ml in 6 (17%). The actuarial freedom from developing Grade 2 proctitis was 75% at 4 years. There was a trend toward increased proctitis with increasing prostate implant doses. Patients with doses < or =70 Gy (n=12) had a 92% freedom from Grade 2 proctitis compared with 67.5% for those with doses delivered to 90% of the gland from a dose-volume histogram of >70 Gy (n=29) (p=0.15). There were no cases of Grade 3 or 4 proctitis. The 3-year actuarial preservation of sexual potency rate was 43%. CONCLUSIONS: The preliminary results from this regimen show an improvement in PSA control for this group of locally advanced prostate cancer patients over more standard therapies. To maximize control while minimizing toxicity, doses of 65-70 Gy of 103Pd should be used when 59.4 Gy of three-dimensional EBRT is delivered. Longer follow-up will be needed to further substantiate these findings.     

Distant and local recurrence in patients with biochemical failure after prostate brachytherapy

PURPOSE: To analyze the patterns of failure after the brachytherapy management of localized prostate cancer. METHODS AND MATERIALS: From 1990 to 2008, 2869 patients underwent prostate brachytherapy and 213 experienced a prostate-specific antigen (PSA) failure by the Phoenix definition. Of these 213 patients, 33.5% were low, 18.5% intermediate, and 58% high risk. RESULTS: Of the 119 patients biopsied, 36 (30%) had a least one positive posttreatment biopsy. In univariate and multivariate analyses, PSA doubling time was the most predictive of a positive biopsy. Patients with doubling times < or =3, >3-6, > or =6-10, and >10 months had positive biopsy rates of 9%, 18%, 36%, and 42%, respectively (p=0.01). The actuarial rate of remaining free from distant metastases at 10 years was 73%. Patients with PSA doubling times of < or =3, >3-6, >6-10, and >10 months had freedom from distant metastases rates of 0%, 74%, 78%, and 94.5% at 10 years, respectively (p<0.0001). In multivariate analysis, PSA doubling time and time to PSA failure were the most significant predictors of developing distant metastases. CONCLUSIONS: About one third of patients harbor a component of local failure and one fourth demonstrate clinical metastases. PSA doubling time can be used to help predict the source of a rising PSA.     

Diagnostic and prognostic value of serum prostate specific antigen in prostate carcinoma

The upper normal limit of serum prostate specific antigen (PSA) of 4 ng/ml is positively evaluated since it discriminates a large percentage of patients having prostate cancer. The PSA limit of 2.5 ng/ml may be used accordingly for patients younger than 50 years of age. The PSA range of 3.3-4 ng/ml may indicate a percentage of patients positive for prostate carcinoma. The PSA above 10 ng/ml indicates that patients have prostate carcinoma by more than 50 %, which is more than double as compared to patients having PSA limits between 4.1-10 ng/ml. It is important to repeat doubtful PSA tests after 3-4 months. If within a year an increase in PSA of more than 2 ng/ml is detected, a high risk of death from prostate cancer is expected. The time for doubling PSA values within a year is described as "velocity index". As for free PSA, this test is not often applied in many nuclear medicine centers. According to the Mayo Clinic, USA, instructions, when total PSA is 2-3.9 ng/ml and free PSA above 18% of these values, the possibility of prostate cancer is less than 10%. On the contrary, for the above total PSA values, if free PSA is less than 10% of these values, the possibility of prostate cancer increases to more than 30%. It is suggested that PSA values be expressed per g of prostate tissue in order to relate to prostate volume. However, one should have in mind that prostate carcinomas have less PSA per g than hyperthophic glands and their volume is usually larger. There are cases where treatment of prostate hypertrophy with finasteride or treatment of prostate cancer with anticancer drugs, may induce a false low PSA. More information about the practical importance of PSA values is expected after 2 or 3 years when a study by the National Cancer Institute of USA on 74,000 men will be completed.     

Medium-term oncological and functional outcomes of hemi-gland brachytherapy using iodine-125 seeds for intermediate-risk unilateral prostate cancer

PURPOSETo examine medium-term outcomes of hemi-gland low-dose-rate brachytherapy as a primary treatment for intermediate-risk prostate cancer.METHODSWe recruited intermediate-risk unilateral prostate cancer patients for a prospective trial of hemi-gland brachytherapy. Twenty-four patients underwent hemi-gland iodine-125 seed implantation with a prescribed dose of 160 Gy. Serum prostate-specific antigen (PSA) was measured regularly and follow-up biopsy was scheduled after 2–3 years of treatment. When clinically needed afterward, for-cause biopsy was performed to confirm pathology. Treatment failure (TF)-free survival, which was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality, was assessed, as was biochemical failure (BF)-free survival. Urinary and sexual functions were also evaluated.RESULTSMedian follow-up duration was 61 months. Twenty-two patients (92%) exhibited a declining trend or decreased value of PSA for 12 months or longer after the treatment. Follow-up biopsy in the initial triennium and for-cause biopsy in the subsequent triennium were performed in 16 and four patients, respectively, and cancer was found from the treated lobe in one patient (4% of the cohort) and significant cancer was found from untreated lobes in four patients (17%) in total. Secondary treatments were performed in six patients successfully. Five-year freedom from BF, TF, and metastasis was 71%, 90%, and 100%, respectively. The International Prostate Symptom Score significantly deteriorated at 3 months and reversed itself afterward. The International Index of Erectile Function 5 had no significant decrease.CONCLUSIONSHemi-gland low-dose-rate brachytherapy provides favorable medium-term oncological outcomes with genito-urinary functional preservation for men with intermediate-risk unilateral prostate cancer.     

External radiotherapy and permanent prostate brachytherapy in patients with localized prostate cancer

We examined the difference in prostate-specific antigen (PSA)-freedom from recurrence (FFR) in patients with localized prostate cancer treated with permanent prostate brachytherapy (PPB) alone or external radiotherapy combined with PPB (RT-PPB). A total of 1476 patients with prostate cancer (T1/T2) were treated with PPB by following the American Brachytherapy Society criteria. Patient self-selection and preference allowed for an overlap of treatment methodologies and risk factors. Monotherapy consisted of 125I or 103Pd. RT-PPB consisted of RT followed by PPB. PSA-FFR was based on a published modification of the American Society for Therapeutic Radiology and Oncology definition. Cox regression analysis was performed to assess the role of Gleason sum, pretreatment PSA value, clinical stage, RT-PPB, the addition of hormones, and the minimum dose covering 90% of the prostate volume (D90 dose). Monotherapy was used for 1016 patients (79%), and RT-PPB was used for 281 patients (21%), with an overall 6-year PSA-FFR of 83.2% (median follow-up of 34.7 months; range, 6-91 months). Multivariate Cox regression analysis to predict PSA-FFR identified the following highly significant variables: pretreatment PSA value, Gleason sum, and the addition of hormones. When the D90% (D90 dose relative to the prescribed dose) was included as a variable, Cox regression identified only the following significant variables: D90%, pretreatment PSA, and Gleason sum. Cox regression failed to identify an improvement in PSA-FFR with RT-PPB or the addition of hormones. Although these conclusions question the role for RT-PPB, only a comparative trial will be able to answer this question definitively.     

Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer

PURPOSE: To analyze the long-term effect of local dose escalation using conformal hypofractionated high-dose-rate brachytherapy (HDR-BT) boost and pelvic external-beam radiation therapy (EBRT) in hormone-na?ve men with localized prostate cancer. PATIENTS AND METHODS: A total of 579 men were consecutively treated with pelvic EBRT and dose escalating HDR-BT since 1986 in two prospective trials: 378 patients at William Beaumont Hospital (1991-2002), and 201 patients at Kiel University (1986-1999). BT optimization was done modulating both, the dwell times and spatial source positions. A short course of neoadjuvant/concurrent androgen deprivation therapy was given to 222 patients. Hormone-na?ve patients only (n = 324) with a follow-up > or = 18 months were analyzed. All patients had at least one poor prognostic factor (stage > or = T2b, Gleason Score > or = 7, pretreatment prostate-specific antigen [PSA] > or = 10 ng/ml): any one factor 122 patients, any two factors 122 patients, and three factors 80 patients. This cohort was stratified by equivalent dose (ED): dose level 1, < or = 94 Gy, n = 58, and dose level 2, > 94 Gy, n = 266, assuming an alpha/beta ratio of 1.2. The ASTRO definition for biochemical failure was used. RESULTS: Mean follow-up was 5.3 years (1.5-13.9 years). For all 324 patients, the 5-year biochemical control (BC) rate was 79%. Cancer-specific survival was 98%, and overall survival 90%. Similar analysis by institution demonstrated no difference in outcomes. For the entire cohort of hormone-na?ve men, dose escalation to > 94 Gy resulted in a better 5-year BC of 59% versus 85% (p < 0.001). Discriminating by risk group a striking dose escalation effect was seen in the groups with two or three poor prognostic factors (p = 0.022 and < 0.001, respectively). In the group with only one poor prognostic factor, no statistical difference could be detected questioning the need for ED > 94 Gy. CONCLUSION: The results demonstrate that conformal HDR-BT is a successful method for delivering very high radiation dose to the prostate. The ability to escalate dose to ED > 94 Gy was reflected in improved long-term outcomes in terms of BC, significantly for those patients with two or three poor prognostic factors reaching BC rates of 85%.