5-year bRFS Rate Research Articles

Clinical factors predicting the outcome of salvage radiotherapy for patients with biochemical recurrence after radical prostatectomy.

It remains unclear which patients with biochemical recurrence after prostatectomy are most suitable for salvage radiotherapy. We evaluated the parameters related to outcomes. We retrospectively evaluated patients who underwent salvage therapy for biochemical recurrence after prostatectomy between 2005 and 2019. This study aimed to evaluate biochemical recurrence-free survival (bRFS) after salvage radiotherapy and elucidate the parameters associated with bRFS. The bRFS rate was calculated using the Kaplan-Meier method, and the parameters associated with bRFS were evaluated using Cox regression analysis. This study included 67 patients treated with salvage radiotherapy with a median age of 67years at salvage radiotherapy. The median follow-up period after salvage radiotherapy was 7.3years. The 5-year bRFS rate following salvage radiotherapy was 47.1%. Univariate analysis showed that PSA doubling time < 6months, positive surgical margin, and pathological Gleason score ≥ 8 were significantly associated with shorter bRFS (p < 0.001, p = 0.036, p = 0.047, respectively). Multivariable analysis showed that a PSA doubling time < 6months and positive surgical margins were significantly associated with shorter bRFS (p = 0.001 and p = 0.018, respectively). No serious adverse events were observed. In our hospital, approximately half of the patients are under long-term control with salvage radiotherapy. A PSA doubling time of < 6months and positive surgical margins were suggested to be associated with poor outcomes of salvage radiotherapy.

CAPRA-S ile radikal prostatektomi sonrası biyokimyasal rekürrens zamanı arasındaki ilişki

Objective: In this study, we aimed to evaluate the relationship between biochemical recurrence time and the “cancer of the prostate risk assessment post-surgery” score (CAPRA-S) after radical prostatectomy (RP). Material and Methods: Retrospective evaluation was made of the records of 328 patients applied with RP for a diagnosis of clinically localized prostate cancer. The patients were separated into groups according to the CAPRA-S score determined according to the preoperative PSA level and pathological characteristics of the RP specimen and the biochemical recurrence time after RP. Results: The mean follow-up period was 76.9±34.5 months. Biochemical recurrence was determined in 23.2% (n:69) of the cases, as early recurrence in 71% (n:49) and late in 29% (n:20). According to the CAPRA-S score, 186 (62.4%) patients were classified as low risk, 66 (22.1%) as moderate risk, and 46 (15%) as high risk. The 3 and 5-year BRFS rates of all the patients were 88.9% and 81.8% respectively. Patients with a low CAPRA-S score were determined to have a statistically significantly higher 3 and 5-year BRFS rate than patients in the moderate and high groups. Early biochemical recurrence after RP was statistically significantly correlated only with lymph node involvement (OR: 2.42, 95% CI: 1.07-5.47, p=0.03). Conclusion: This study showed that the CAPRA-S score, which is effective in predicting the risk of biochemical recurrence after RP, was not effective in predicting the time of biochemical recurrence after RP. Keywords: Biochemical recurrence, CAPRA-S score, prostate cancer, radical prostatectomy

High-dose-rate fractionated brachytherapy monotherapy for localized prostate cancer: a systematic review and meta-analysis.

PurposeHigh-dose-rate (HDR) brachytherapy as primary therapy (monotherapy) is a standard National Comprehensive Cancer Network (NCCN) endorsed treatment option for patients with localized prostate cancer. Thus far, most data are limited to single-institution experiences. Accordingly, we sought to systematically review rates of biochemical recurrence-free survival (bRFS) and toxicity associated with fractionated HDR monotherapy.Material and methodsA systematic review was performed using PubMed and Embase databases for relevant articles published between January 1999 and December 2019, according to preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. Included studies were limited to fractionated HDR monotherapy publications in full manuscript form with at least 5-year median follow-up, at least 80 patients included, and adequate reporting of bRFS and toxicity data. Meta-analyses were performed with random-effect modeling. Extent of heterogeneity between studies was determined using I2 and Cochran’s Q tests.ResultsSeven unique studies were identified, including 2,123 patients. NCCN low-, intermediate-, and high-risk patients comprised 40%, 40%, and 20% of patients, respectively. Median follow-up at the study group level was 74 months (range, 60-131 months). The 5-year bRFS rate was 95% (95% confidence interval [CI]: 93-96%), and after adjusting to control for publication bias, it was 96% (95% CI: 94-99%). Estimated adjusted late grade ≥ 3 genitourinary and gastrointestinal toxicity rates were 2% (95% CI: 1-4%) and 0.3% (95% CI: 0-1.1%), respectively.ConclusionsFractionated HDR monotherapy is associated with high rates of disease control and low rates of toxicity. Future studies are needed to better define the value of this treatment modality relative to other options.

Five-Year Clinical Outcomes Of 51.6Gy (RBE) In 12-Fractionated Carbon-Ion Radiotherapy For Localized Prostate Cancer: Two Prospective Analyses

Although 51.6 Gy (relative biological effect [RBE]) in 12-fractionated over a 3-weeks carbon-ion radiotherapy (CIRT) has been performed from 2010 and is now regarded as standard CIRT treatment, there is no report of clinical outcomes with long term follow-up after CIRT using the dose prescription. The purpose of this study was to reveal the clinical outcome after CIRT of the dose prescription with median follow up duration more than 5 years at our institution. A total of 257 patients with localized prostate cancer who received CIRT of 51.6 Gy (RBE) in 12 fractions in two protocols (9904-4 and 1002) between July 2010 and February 2014 were analyzed. Biochemical relapse free survival (bRFS) defined by the Phoenix definition and the survival rates were calculated. The incidence of acute and late adverse events was evaluated based on the Common Terminology Criteria for Adverse Events ver. 4.0. The numbers of low-, intermediate-, and high-risk group patients was 41(15.9%), 112(43.6%), and 104(40.5%), respectively. The median follow-up period of the surviving patients was 6.0years (range, 1.1-9.5years). The 5-year bRFS rates of the low-, intermediate, high-risk groups were 94.7%,92.1%, and 92.5%, respectively. The disease specific survival of the entire group was 100%. The acute and late gastrointestinal (GI) G2 toxicities were 0 and 2 (0.8%), respectively. The acute and late genitourinary (GU) G2 toxicities were 16 (6.2%) and 3 (1.2%), respectively, including the acute and late G2 hematuria of 1 (0.4%) and 1 (0.4%), respectively. None ≥G3 toxicities were observed. The 12-fractionated CIRT of 51.6Gy (RBE) for localized prostate cancer was good therapeutic and showed low toxicity.

Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer

The aim of this observational study is to investigate whether local consolidative treatment delivered to the primary site and metastatic tumour burden may add survival benefit to de novo oligometastatic prostate cancer (Oligo-PCa) patients. We retrospectively reviewed all Oligo-PCa patients treated with radiotherapy to the primary tumor sites and metastatic tumor burden at our institution between March 2010 and June 2019. All patients having ≤ 5 metastases involving nodes and/or bones, loco-regional and/or extra-pelvic sites, were included. Most of the patients had started androgen deprivation therapy with or without docetaxel as standard of care before radiotherapy. The Kaplan Meier analysis was performed to estimate survival outcomes. The univariate analysis tested possible prognostic factors increasing the rate of biochemical relapse. We analysed 37 Oligo-PCa patients. Twenty-eight (75.7%) had loco-regional metastases, in 9 patients (24.3%) the metastatic tumour burden was extra-pelvic. Nineteen (51.4%) had bone metastases, 21 (56.8%) nodal involvement and 7 (18.9%) both. Twenty (54.1%) had a single metastasis. The median follow-up was 55.5 months. The median overall survival (OS) was 68.8 months, the 2- and 5-year OS rates were 96.9% and 65.4%. The median biochemical relapse free survival (b-RFS) was 58 months and the 2- and 5-year b-RFS rates were 73.3% and 39.3%. The 2- and 5-year local relapse free survival rates were 93.9% and 83.7%. On the univariate analysis post-treatment PSA level ≤ 1 ng/ml was significantly related with the b-RFS (p = 0.004). Curative approach in Oligo-PCa patients involving both the primary tumor and metastatic sites may be feasible and well tolerate. Many patients presented longer survival and PSA at first follow-up was the most important prognostic factor. Further trials are needed to confirm our results and to evaluate if patients with PSA at first follow-up > 1 ng/ml may benefit from further treatments.

Five-year results of post-prostatectomy patients administered a hydrogel rectal spacer implant in conjunction with dose escalated external beam radiation therapy

This study reports on the 5-year biochemical-relapse free survival (bRFS), and late gastrointestinal (GI) and genitourinary (GU) toxicities of patients who underwent a prostatectomy and received high dose (> 72 Gy) radiation therapy with an absorbable polyethylene glycol (PEG) rectal spacer implant. From January 2010 to October 2013, 21 radical prostatectomy patients received a PEG spacer. GI and GU toxicities were scored using the National Cancer Center Institute Common Terminology Criteria for Adverse Events v4.0 grading scheme. bRFS was tallied and segregated into risk groups according to the National Cancer Comprehensive Network (NCCN) guidelines version 1.2016. Cox regression multivariate analysis was performed to elicit disease risk factors. The mean follow-up time was 59 months (SD 12, range 40–97). Our GI toxicities for acute, 3 months, and after 6 months are as follows: grade 0 (57%, 86%, 86%), grade 1 (43%, 14%, 14%), and grade 2 (0%, 0%, 5%). Our GU toxicities for acute, 3 months, and after 6 months are as follows: grade 0 (43%, 48%, 62%), grade 1 (48%, 43%, 24%), and grade 2 (10%, 5%, 14%). There were no late grade 3 GI/GU toxicities. The 5-year overall bRFS rate was 62.2% (95% CI 42.6–90.9%, SE 12.0%). Multivariate logistic regression analysis revealed positive surgical resection margins to be predictive (p = 0.00037) for decreased biochemical control. Hydrogel rectal spacer implants in patients who previously had a prostatectomy is well tolerated long term with reduced incidence of GI and GU toxicities, and bRFS rates consistent with previous reports in the literature.

Long-term Outcomes of Radiotherapy Regimen of 72 Gy in 30 Fractions for Prostate Cancer.

The long-term efficacy and safety of moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT) in prostate cancer remains uncertain. This study aimed to evaluate MH-IMRT regimen of 72 Gy in 30 fractions in patients with prostate cancer. The outcomes of 412 consecutive prostate cancer patients, who received MH-IMRT between May 2007 and December 2012, were retrospectively reviewed. The median patient age was 70.9 (range=50-84) years. Late gastrointestinal (GI) and genitourinary (GU) toxicity rates were evaluated according to the CTCAE ver. 3.0. The overall survival, biochemical relapse-free survival rate (bRFS), late GI toxicity, and GU toxicity rates were analyzed with the Kaplan-Meier method. The median follow-up was 71.5 (range, 1.4-124.8) months. The 5-year bRFS rate was 93.2%. The 5-year grade ≥2 late GI and GU toxicity rates were 3.3% and 4.5%, respectively. MH-IMRT regimen of 72 Gy in 30 fractions was effective and safe for prostate cancer patients.

Long-term outcome of a moderately hypofractionated, intensity-modulated radiotherapy approach using an endorectal balloon for patients with localized prostate cancer

BackgroundTechnical advances in radiotherapy delivery have simultaneously enabled dose escalation and enhanced bladder and rectal sparing. However, the optimal radiation fractionation regimen for localized prostate cancer is unclear. Laboratory and clinical evidence suggest that hypofractionation may improve the therapeutic ratio of radiotherapy. We report our institutional outcomes using moderately hypofractionated, intensity-modulated radiotherapy (IMRT), and an endorectal balloon, with emphasis on long-term biochemical control and treatment-related adverse events in patients with localized prostate cancer.MethodsBetween January 1997 and April 2004, 596 patients with cT1–T3 prostate cancer underwent IMRT using a moderate hypofractionation regimen (76.70 Gy at 2.19 Gy/fraction) with an endorectal balloon. Using D’Amico classification, 226 (37.9%), 264 (44.3%), and 106 (17.8%) patients had low-, intermediate-, or high-risk disease, respectively. The majority of intermediate- and high-risk patients received androgen deprivation therapy. Biochemical relapse-free survival (bRFS) was evaluated using 2005 Phoenix criteria and estimated using the Kaplan–Meier method.ResultsThe median follow-up was 62 months. Overall 5- and 10-year bRFS rates were 92.7% and 87.7%. For low-, intermediate-, and high-risk patients, the 5-year bRFS rates were 96.9%, 93.3%, and 82.0%, respectively; the 10-year bRFS rates were 91.4%, 89.3%, and 76.2%, respectively. Prostate-specific antigen, Gleason score, and T stage were significant predictors of bRFS (all P < 0.01). The 5-year rates of severe (≥ Grade 3) adverse events were very low: 1.2% for gastrointestinal events and 1.1% for genitourinary events.ConclusionsLong-term outcomes after moderately hypofractionated IMRT are encouraging. Moderate hypofractionation represents a safe, efficacious, alternative regimen in the treatment of localized prostate cancer.

Manual vs. automated implantation of seeds in prostate brachytherapy: Oncologic results from a single-center study

PurposeThe objective of this study was to study survival and tolerance of prostate cancer patients treated with 125I permanent interstitial brachytherapy by automated vs. manual implantation of seeds. Methods and MaterialsBetween 2002 and 2010, 349 selected patients were treated with 125I brachytherapy by the same team: from 2002 to April 2005, 65 patients with linked seeds and then 284 patients treated using Nucletron First System automated implantation. We analyzed biochemical recurrence-free survival (bRFS) rates and toxicities (univariate and multivariate analyses). ResultsTwo hundred seventy-seven (79.4%) and 69 patients (19.8%) with low- and intermediate-risk disease were treated, respectively (median follow-up: 64 months). The 5-year bRFS rate was 93.1% (95% confidence interval 89.3–95.6) for the entire cohort. The 5-year bRFS rates were 93.4% and 91.7% for patients with low- and intermediate-risk disease, respectively (p = 0.42). In univariate and multivariate analyses, there was no statistically significant difference in the 5-year bRFS rate depending on the implantation technique (93.1% vs. 91.8%, respectively, for automated and linked seeds; p = 0.53). In univariate analysis, only D90 prostate (dose delivered to 90% of the prostate) <140 Gy (p = 0.01), lack of prostate-specific antigen bounce (p = 0.008), and nadir prostate-specific antigen >0.11 (p = 0.01) were predictive factors for bRFS. We observed Grade 3 urethritis in 7 patients (2%), urinary incontinence in 2 patients (0.7%), and Grade 4 proctitis in 2 patients (0.7%). ConclusionsIn this large single-center series, brachytherapy for selected localized prostate cancer achieved excellent rates of biochemical control at 5 years (93.1%) with an acceptable toxicity profile, irrespective of the implantation technique used.

Prostate specific antigen five years following stereotactic body radiation therapy (SBRT) for low and intermediate risk prostate cancer: An ablative procedure?

123 Background: Our previous work on early PSA kinetics following prostate SBRT showed that an initial rapid and then slow PSA decline may result in very low PSA nadirs. This retrospective study sought to evaluate the PSA nadir 5 years following SBRT for low and intermediate risk prostate cancer (PCa). Methods: 65 low and 80 intermediate risk PCa patients were treated definitively with SBRT at Georgetown University Hospital between January 2008 and October 2011. All patients were treated to 35-37.5 Gy in 5 fractions delivered via the CyberKnife Radiosurgical System. Patients who received androgen deprivation therapy were excluded from this study. Pre- and post-treatment PSA and total testosterone levels were obtained during routine follow up visits. Biochemical relapse was defined as a PSA rise &gt; 2 ng/mL above the nadir and analyzed using the Kaplan Meier method. The PSA nadir was defined as the lowest PSA value prior to biochemical relapse or as the lowest value recorded during follow up. Prostate ablation was defined as a PSA nadir &lt; 0.2 ng/mL. Univariate logistic regression analysis was used to evaluate relevant variables on the likelihood of achieving a PSA nadir &lt; 0.2 ng/mL. Results: The median age at the start of SBRT was 72 years. These patients had a median prostate volume of 36 cc with a median 25% of total cores involved. At a median follow up of 5.8 years, 84% and 37% of patients achieved a PSA nadir ≤ 0.5 ng/mL and &lt; 0.2 ng/mL, respectively. Five low and 8 intermediate risk patients experienced a biochemical relapse; those who did not experience a biochemical relapse, achieved a median PSA nadir of 0.2 ng/mL. There was no difference between the 5-year bRFS rate for low (96.6%) and intermediate risk (97.4%) patients and the median time to PSA nadir was 36 months. Initial PSA (p = 0.024) and a lower testosterone at the time of the PSA nadir (p = 0.049) were found to be significant predictors of achieving a PSA nadir &lt; 0.2 ng/mL. Conclusions: SBRT for low and intermediate risk PCa is a convenient treatment option with low PSA nadirs and a high rate of early bRFS. Less than 40% of patients achieved an ablative PSA nadir. Thus, the role of further dose escalation is an area of active investigation.

Outcomes for prostate glands >60 cc treated with low-dose-rate brachytherapy

PurposeWe sought to analyze whether outcomes of biochemical relapse–free survival (bRFS), late genitourinary (GU), and late gastrointestinal toxicity are different for prostate cancer patients with small (≤60 cc) vs. large (>60 cc) prostates following low dose-rate brachytherapy. Methods and MaterialsThe bRFS outcomes for 2076 low- or intermediate-risk prostate cancer patients from 1996 to 2012 were determined from a review of a prospectively maintained database. All patients were treated with 125I monotherapy without androgen deprivation therapy. Biochemical failure was defined per the Phoenix definition. Patient-related factors and dosimetric values were examined in Cox regression analyses for bRFS and late toxicity. Late toxicity was scored according to a modified Common Terminology Criteria for Adverse Events version 4.0 scale. ResultsThe median followup for all patients was 55 months. The 5-year bRFS rates for all patients, prostates >60 cc, and prostates ≤60 cc were 93.4% (95% confidence interval [CI]: 92.1%, 94.7%), 96.7% (95% CI: 94.4%, 98.9%), and 92.9% (95% CI: 91.4%, 94.3%), respectively. On multivariable analysis, prostate size >60 cc was significantly associated with improved bRFS (p = 0.01), as were initial prostate-specific antigen and biopsy Gleason score (p < 0.0001 and p = 0.0002, respectively). Patients with prostates >60 cc had significantly higher rates of Grade 3–4 late GU toxicity at 5 years than patients with smaller prostates; 7.2% (95% CI: 4.0%, 10.4%) and 3.2% (95% CI: 2.3%, 4.1%), respectively (p = 0.0007). The overall late gastrointestinal toxicity rate for all patients was 0.7% at 5 years with no significant difference between the two groups. ConclusionsImplantation of large prostates >60 cc results in favorable bRFS outcomes and is associated with increased but acceptable rates of Grade 3 and higher late GU toxicities.

Adjuvant radiotherapy after prostatectomy for prostate cancer in Japan: a multi-institutional survey study of the JROSG.

In Japan, the use of adjuvant radiotherapy after prostatectomy for prostate cancer has not increased compared with the use of salvage radiotherapy. We retrospectively evaluated the outcome of adjuvant radiotherapy together with prognostic factors of outcome in Japan. Between 2005 and 2007, a total of 87 patients were referred for adjuvant radiotherapy in 23 institutions [median age: 64 years (54–77 years), median initial prostate-specific antigen: 11.0 ng/ml (2.9–284 ng/ml), Gleason score (GS): 6, 7, 8, 9, 10 = 13.8, 35.6, 23.0, 27.6, 0%, respectively]. Rates of positive marginal status, seminal vesicle invasion (SVI) and extra-prostatic extension (EPE) were 74%, 26% and 64%, respectively. Median post-operative PSA nadir: 0.167 ng/ml (0–2.51 ng/ml). Median time from surgery to radiotherapy was 3 months (1–6 months). A total dose of ≥60 Gy and <65 Gy was administered to 69% of patients. The median follow-up time was 62 months. The 3- and 5-year biochemical relapse-free survival (bRFS) rates for all patients were 66.5% and 57.1%, respectively. The GS and marginal status (P = 0.019), GS and SVI (P = 0.001), marginal status and EPE (P = 0.017), type of hormonal therapy and total dose (P = 0.026) were significantly related. The 5-year bRFS rate was significantly higher in SVI-negative patients than SVI-positive patients (P = 0.001), and significantly higher in patients with post-operative PSA nadir ≤0.2 than in patients with post-operative PSA nadir >0.2 (P = 0.02), and tended to be more favorable after radiotherapy ≤3 months from surgery than >3 months from surgery (P = 0.069). Multivariate analysis identified SVI and post-operative PSA nadir as independent prognostic factors for bRFS (P = 0.001 and 0.018, respectively).

Stereotactic body radiotherapy for localized prostate cancer: Pooled analysis from a multi-institutional consortium of prospective phase II trials

PurposeThe effectiveness of stereotactic body radiotherapy (SBRT) for localized prostate cancer is tested. Methods and materialsA total of 1100 patients with clinically localized prostate cancer were enrolled in separate prospective phase 2 clinical trials of SBRT from 8 institutions during 2003–11 and pooled for analysis. SBRT using the CyberKnife delivered a median dose of 36.25Gy in 4–5 fractions. Patients were low-risk (58%), intermediate-risk (30%) and high-risk (11%). A short-course of androgen deprivation therapy (ADT) was given to 14%. PSA relapse defined as a rise >2ng/ml above nadir was analyzed with the Kaplan Meier method. ResultsWith a median follow-up of 36months there were 49 patients with PSA failure (4.5%), 9 of whom were subsequently determined to be benign PSA bounces. The 5-year biochemical relapse free survival (bRFS) rate was 93% for all patients; 95%, 83% and 78% for GS ⩽6, 7 and ⩾8, respectively (p=0.001), and 95%, 84% and 81% for low-, intermediate- and high-risk patients, respectively (p<0.001). No differences were observed with ADT (p=0.71) or as a function of total dose (p=0.17). A PSA bounce of >0.2ng/ml was noted among 16% of patients. For 135 patients possessing a minimum of 5years follow-up, the 5-year bRFS rate for low- and intermediate-risk patients was 99% and 93%, respectively. ConclusionPSA relapse-free survival rates after SBRT compare favorably with other definitive treatments for low and intermediate risk patients. The current evidence supports consideration of SBRT among the therapeutic options for these patients.

Long-term efficacy of stereotactic body radiotherapy for localized prostate cancer: A multi-institutional pooled analysis.

9 Background: The purpose of this study is to report biochemical relapse-free survival (bRFS) rates for a group of localized prostate cancer patients from a pooled multi-institutional dataset with at least 5 years follow-up after stereotactic body radiotherapy (SBRT). Methods: The outcome data from 1101 patients treated with SBRT between 2003 and 2011 were pooled from 8 institutions. A subset of 135 cases had a minimum 5 years follow-up. All 135 cases had clinical stage T1 or T2A disease. The distribution by Gleason score (GS) was &lt;6 in 80% and 7 in 20%. The median pretreatment PSA (iPSA) level was 5.1 ng/ml (range: 0.1-27.8). The distribution by risk was 77% low, 21% intermediate, and 2% high risk. The median dose was 36.25 Gy (35-40 Gy range) delivered either with 4 or 5 fractions. The prescribed dose groups were as follows: 35 Gy in 42%, 36.25 Gy in 47%, and &gt;38 Gy in 11%. Androgen deprivation therapy was given to 21% of patients. Biochemical relapse, defined as a rise &gt; 2 ng/ml above nadir, was determined in a total of 4 failures. Results: The median follow-up for all 135 cases was 60 months (range 60 to 72). For all patients, the bRFS rate at 5 years was 97%. The 5-year actuarial bRFS rates for GS &lt; 6, and Gleason score 7 were 98%, and 92%, respectively (p=0.15). The 5-year actuarial bRFS rates for low versus intermediate/high-risk patients were 99% and 93%, respectively (p=0.11). The 5-year actuarial bRFS rates for patients receiving 35 Gy versus &gt;36.25 Gy were 93% and 100%. No difference in bRFS was observed with the use of androgen deprivation (p=0.78). Multivariate analysis showed only GS to be an independent predictor of relapse (p=0.03); iPSA (p=0.10) and radiation dose (0.97) were not. Conclusions: In a relatively large cohort of localized prostate cancer patients treated with SBRT, long follow-up period (&gt;5 years), excellent efficacy was demonstrated with 97% of patients being free from relapse. For low and intermediate risk cases, these results compare favorably with other modalities with similar follow-up periods. Although a trend for worse outcome was seen with total radiation doses of 35 Gy, this was not confirmed on multivariate analysis.

Stereotactic Body Radiation Therapy for Intermediate-risk Organ-confined Prostate Cancer: Interim Toxicity and Quality of Life Outcomes From a Multi-institutional Study

observed in 16% of the patients at a median of 36 months (range 6-60 months). The median bounce magnitude was 0.505 ng/mL (range 0.2-5.29 ng/mL). For the 335 cases with a minimum of 4 years of follow-up (median 53 months), the 5-year bRFS rates for low-risk and intermediaterisk cases were 97% and 89%, respectively. Conclusions: With a large cohort of patients treated with stereotactic body radiation therapy, with a reasonably long follow-up period, excellent efficacy was demonstrated at 5 years. For high-risk cases, the results are preliminary, given the small number of cases treated. However, for low and intermediate risk cases, these results compare favorably with other modalities. These results support a low alpha beta ratio for prostate cancer. Author Disclosure: A. Katz: F. Honoraria; Accuray. D. Freeman: F. Honoraria; Accuray. J. Aronovitz: None. D. Fuller: None. G. Bolzicco: None. R. Meier: None. S. Collins: G. Consultant; Accuray. J. Wang: None. M. Steinberg: None. C. King: None.

High-Dose-Rate Brachytherapy Combined With External Beam Radiotherapy for Localized Prostate Cancer: Clinical Predictive Factor for Biochemical Relapse-Free Survival

Purpose: The aim of this study is to determine what kind of clinical factors were predictive for biochemical relapse-free survival (bRFS) of prostate cancer (CaP) patients treated with high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT).Materials and Methods: Between July 1999 and September 2007, 15, 51 and 41 patients considered as low-risk group (stage < or = T2a, PSA < or = 10 ng/mL, and Gleason score (GS) < or = 6), intermediate-risk group (stage = T2b, 10 < PSA < or = 20 ng/mL, or GS = 7), and high-risk group (stage > or = T2c, PSA >20 ng/mL, or Gleason score > or = 8), respectively, were treated with HDR-BT followed by EBRT at Kochi Medical School Hospital in Japan. Patient age ranged from 55 to 81 years (median 71). Forty-two patients had received neoadjuvant hormonal therapy, which was stopped at the beginning of radiotherapy in all cases. Patients were treated with EBRT to 39–45 Gy in 13–25 fractions, and HDR-BT to 18 Gy in 2–3 fractions for prostate. Adjuvant hormonal therapy was not performed until biochemical failure or clinical recurrence became apparent. PSA failure was defined as the Phoenix definition of nadir + 2ng/mL. The bRFS rates were estimated using the Kaplan-Meier method. The median followup was 60 months (range, 36 – 134 months). Cox proportional hazards regression analysis was used for univariate and multivariate analyses examining these factors in relation to bRFS: clinical T stage, initial PSA level, GS and use of neoadjuvant hormonal therapy. A two-side p value of <0.05 was considered statistically-significant.Results: The 5-year bRFS rate in low-, intermediate- and high-risk group were 100%, 97.9%, and 83.7%, respectively. The 5-year bRFS rate in high-risk group was statistically inferior to that in intermediate-risk group (p = 0.0206). On univariate and multivariate analyses, clinical T state remained an independent predictor of bRES. None of initial PSA level, GS, or use of neoadjuvant hormonal therapy was not predictive factor for bRFS of CaP patient with HDR-BT combined with EBRT.Conclusions: Clinical T3 CaP carried a worse bRFS than clinical T1-2 Cap. For the improvement of bRFS in T3Cap, adjuvant hormonal therapy may be needed for HDR-BT combined with EBRT. Purpose: The aim of this study is to determine what kind of clinical factors were predictive for biochemical relapse-free survival (bRFS) of prostate cancer (CaP) patients treated with high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT). Materials and Methods: Between July 1999 and September 2007, 15, 51 and 41 patients considered as low-risk group (stage < or = T2a, PSA < or = 10 ng/mL, and Gleason score (GS) < or = 6), intermediate-risk group (stage = T2b, 10 < PSA < or = 20 ng/mL, or GS = 7), and high-risk group (stage > or = T2c, PSA >20 ng/mL, or Gleason score > or = 8), respectively, were treated with HDR-BT followed by EBRT at Kochi Medical School Hospital in Japan. Patient age ranged from 55 to 81 years (median 71). Forty-two patients had received neoadjuvant hormonal therapy, which was stopped at the beginning of radiotherapy in all cases. Patients were treated with EBRT to 39–45 Gy in 13–25 fractions, and HDR-BT to 18 Gy in 2–3 fractions for prostate. Adjuvant hormonal therapy was not performed until biochemical failure or clinical recurrence became apparent. PSA failure was defined as the Phoenix definition of nadir + 2ng/mL. The bRFS rates were estimated using the Kaplan-Meier method. The median followup was 60 months (range, 36 – 134 months). Cox proportional hazards regression analysis was used for univariate and multivariate analyses examining these factors in relation to bRFS: clinical T stage, initial PSA level, GS and use of neoadjuvant hormonal therapy. A two-side p value of <0.05 was considered statistically-significant. Results: The 5-year bRFS rate in low-, intermediate- and high-risk group were 100%, 97.9%, and 83.7%, respectively. The 5-year bRFS rate in high-risk group was statistically inferior to that in intermediate-risk group (p = 0.0206). On univariate and multivariate analyses, clinical T state remained an independent predictor of bRES. None of initial PSA level, GS, or use of neoadjuvant hormonal therapy was not predictive factor for bRFS of CaP patient with HDR-BT combined with EBRT. Conclusions: Clinical T3 CaP carried a worse bRFS than clinical T1-2 Cap. For the improvement of bRFS in T3Cap, adjuvant hormonal therapy may be needed for HDR-BT combined with EBRT.

Radical Prostatectomy Versus External-Beam Radiotherapy for Localized Prostate Cancer: Long-Term Effect on Biochemical Control—In Search of the Optimal Treatment

The optimal management of patients with clinically localized prostate carcinoma remains undefined due in part to the absence of well-designed, randomized trials. This retrospective study comprised 505 patients diagnosed with low- or intermediate- risk prostate cancer in 1998-2005 and treated at Hospital Gregorio Marañón (Spain) with radical prostatectomy (RP) or external-beam radiotherapy (EBRT). No adjuvant therapy was administered. Biochemical relapse was defined as a prostate-specific antigen (PSA) level ≥0.4 ng/ml for RP cases and nadir + 2 for EBRT cases. RP was performed in 271 patients (53.6%) and EBRT in 234 patients (46.4%). The median follow-up was 60 months. The analysis end point was to compare the biochemical recurrence-free survival (bRFS) between the two groups. The 5-year bRFS rates for RP and EBRT were 79 ± 2% and 86 ± 2%, respectively (P = 0.48). Multivariate analysis indicated that initial PSA (P = 0.00), perineural invasion in the biopsy specimen (P = 0.00), Gleason score (P = 0.04), EBRT dose (P = 0.02), and positive margins (P = 0.00) were independent predictors of relapse. A decision tree model was constructed with these variables. In the EBRT cohort, a nadir PSA of <0.3 ng/ml was associated with the best 5-year bRFS (96.6 vs. 56.5% if nadir PSA > 1.3 ng/ml). Late biochemical failure (>5 years) was more frequent in the RT group and with low-dose EBRT (≤72 Gy). The biochemical failure rates were similar between PR and EBRT in low- and intermediate-risk subgroups. Outcome was determined by classic pre-treatment features, perineural invasion, low-dose EBRT (≤72 Gy), and nadir PSA value in the RT cohort.

PSA Bounce and Biochemical Failure After Brachytherapy for Prostate Cancer: A Study of 820 Patients With a Minimum of 3 Years of Follow-Up

To determine clinical or dosimetric factors associated with a prostate-specific antigen (PSA) bounce, as well as an association between a PSA bounce and biochemical relapse-free survival (bRFS), in patients treated with iodine-125 brachytherapy. A variety of clinical and treatment factors were examined in 820 patients who had a minimum of 3 years of PSA follow-up with T1-T2cN0M0 prostate cancer. Four different PSA threshold values were used for defining a PSA bounce: a PSA rise of ≥ 0.2, ≥ 0.4, ≥ 0.6, and ≥ 0.8 ng/mL. A PSA bounce of ≥ 0.2, ≥ 0.4, ≥ 0.6, and ≥ 0.8 ng/mL was noted in 247 patients (30.1%), 161 (19.6%), 105 (12.8%), and 78 (9.5%), respectively. The median time to the first PSA rise was 17.4, 16.25, 16.23, and 15.71 months, respectively, vs. 34.35 months for a biochemical failure (p < 0.0001). A PSA rise of ≥ 0.2 ng/mL was the only definition for which there was a significant difference in bRFS between bounce and non-bounce patients. The 5-year bRFS rate of patients having a PSA bounce of ≥0.2 was 97.7% vs. 91% for those who did not have a PSA bounce (p = 0.0011). On univariate analysis for biochemical failure, age, risk group, and PSAs per year had a statistically significant correlation with PSA bounce of ≥ 0.2 ng/mL. On multivariate analysis, age and PSAs per year remained statistically significant (p < 0.0001 and p = 0.0456, respectively). A bounce definition of a rise ≥ 0.2 ng/mL is a reliable definition among several other definitions. The time to first PSA rise is the most valuable factor for distinguishing between a bounce and biochemical failure.

Androgen Deprivation Therapy in Patients Treated with External Beam Radiotherapy for High-risk Prostate Cancer in the PSA Era

Androgen Deprivation Therapy in Patients Treated with External Beam Radiotherapy for High-risk Prostate Cancer in the PSA Era

Commentary on Comparison of biochemical relapse-free survival between primary Gleason score 3 and primary Gleason score 4 for biopsy Gleason score 7 prostate cancer

To determine whether the primary grade (PG) of biopsy Gleason score (GS) 7 prostate cancer (CaP) was predictive for biochemical relapse-free survival (bRFS). Most of the present data regarding the PG of GS7 CaP refer to surgical specimens. Our goal was to determine whether the biopsy GS used at the time of medical decision making predicted for the biochemical outcome. We reviewed the data from 705 patients with biopsy GS7 CaP, from a prospectively maintained database, who had been treated at our institution between September 1996 and March 2005 with radical prostatectomy ( n = 310), external beam radiotherapy ( n = 268), or prostate radioactive seed implantation ( n = 127). The bRFS rates were estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used for univariate and multivariate analyses examining these factors in relation to bRFS: PG of biopsy GS, initial prostate-specific antigen level, clinical T stage, use of androgen deprivation, risk group (high or intermediate), and treatment modality. The 5-year bRFS rate was 78% and 71% ( P = 0.0108) for biopsy GS7 PG3 CaP and biopsy GS7 PG4 CaP, respectively. Comparing PG3 and PG4 within treatment modalities, only prostate implantation patients had a significant difference in the 5-year bRFS rate, 88% vs. 76%, respectively ( P = 0.0231). On multivariate analysis, the PG of biopsy GS remained an independent predictor of bRFS, with PG3 having better bRFS than PG4 (relative risk, 0.655; 95% confidence interval, 0.472–0.909; P = 0.0113). Biopsy GS7 PG4 CaP carries a worse bRFS than biopsy GS7 PG3 CaP.