pre-RT Prostate-specific Antigen Level Research Articles

Prognostic factors in postoperative radiotherapy for prostate cancer - tertiary center experience.

BackgroundThe aim of the study was to analyse the prognostic factors in postoperative prostate cancer irradiation and develop a nomogram for disease-free survival (DFS).Patients and methodsThis retrospective study included 236 consecutive prostate cancer patients who had radical prostatectomy followed by radiotherapy (RT) at a single tertiary institution between 2009 and 2014. The main outcome was DFS analysed through uni- and multivariable analysis, Kaplan-Meier curves, log-rank testing, recursive partitioning analysis, and nomogram development.ResultsThe median follow up was 62.3 (interquartile range [IQR] 38.1–79) months. The independent clinical factors associated with increased risk of recurrence or progression in the multivariate analysis (MVA) were prostate-specific antigen (PSA) level before RT, pT3 characteristic, and local failure as salvage indication. The value of PSA nadir had a significant impact on the risk of biochemical failure. Biochemical control and DFS were significantly different depending on treatment indication (p < 0.0001). The recursive partitioning analysis highlighted the importance of the PSA level before RT, Gleason Grade Group, PSA nadir, and local failure as a treatment indication. Finally, the nomogram for DFS was developed and is available online at https://apps.konsta.com.pl/app/prostate-salvage-dfs/.ConclusionsThe Pre-RT PSA level, pT3 characteristic and local failure as salvage indication are pivotal prognostic factors associated with increased risk of recurrence or progression. The Gleason grade group of 4–5 and PSA nadir value allow for further risk stratification. The treatment outcomes in postoperative prostate cancer irradiation are significantly different depending on treatment indication. An online nomogram comprising of both pre-treatment and current data was developed allowing for visualization of changes in prognosis depending on clinical data.

A prospective study of the effect of testosterone escape on preradiotherapy prostate-specific antigen kinetics in prostate cancer patients undergoing neoadjuvant androgen deprivation therapy.

Introduction:Prostate-specific antigen (PSA) kinetic patterns during neoadjuvant androgen deprivation therapy have been shown to predict unfavorable long-term outcomes.Objective:To investigate the effect of testosterone escape (TE) on these kinetic patterns, as this had not been previously reported.Methods:There were 50 consecutive prostate cancer patients who received 6 months of triptorelin prior to definitive radiotherapy (RT). Testosterone and PSA levels were measured at baseline and every 6 weeks. Clinical factors were tested for their ability to predict for TE and unfavorable PSA kinetic patterns. The effects of TE, at both 1.7 and 0.7 nmol/L levels, were analyzed.Results:TE occurred in at least one reading for 14% and 34% of the patients at the 1.7 and 0.7 nmol/L levels, respectively. No baseline factors predicted TE. The median PSA halving time was 25 days and the median pre-RT PSA level was 0.55 ng/mL. The only factor significantly associated with a higher pre-RT PSA level was a higher baseline PSA level. The only factor that significantly predicted a longer PSA halving time was TE at the 1.7 nmol/L level.Conclusions:TE and higher baseline PSA levels may adversely affect PSA kinetics and other outcomes for patients undergoing neoadjuvant hormone therapy prior to radiotherapy. Studies investigating the tailoring of neoadjuvant therapy by extending the duration in those patients with a higher baseline PSA level or by the addition of anti-androgens in those demonstrating TE, should be considered.

Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials

To validate whether prostate-specific antigen (PSA) level after neoadjuvant androgen suppression (neoAS) is associated with long-term outcome after neoAS and external beam radiation therapy (RT) with concurrent short-term androgen suppression (AS) in patients with prostate cancer. This study included 2404 patients. The patients were treated with neoAS before RT and concurrent AS (without post-RT AS) and were pooled from NRG Oncology/RTOG trials 9202, 9408, 9413, and 9910. Multivariable models were used to test associations between the prespecified dichotomized post-neoAS, pre-RT PSA level (≤0.1 vs>0.1ng/mL) groupings, and clinical outcomes. The median follow-up for surviving patients was 9.4years. The median post-neoAS, pre-RT PSA level was 0.3ng/mL, with 32% of patients having levels ≤0.1ng/mL. Race, Gleason score, tumor stage, node stage, pretreatment PSA level, and duration of neoAS were associated with the groups of patients with PSA levels ≤0.1 and>0.1ng/mL. In univariate analyses, post-neoAS, pre-RT PSA level >0.1ng/mL was associated with increased risks of biochemical failure (hazard ratio [HR], 2.04; P<.0001); local failure (HR, 2.51; P<.0001); distant metastases (HR, 1.73; P=.0006); cause-specific mortality (HR, 2.36; P<.0001); and all-cause mortality (HR, 1.24; P=.005). In multivariable models that also included baseline and treatment variables, post-neoAS, pre-RT PSA level >0.1ng/mL was independently associated with increased risk of biochemical failure (HR, 2.00; P<.0001); local failure (HR, 2.33; P<.0001); and cause-specific mortality (HR, 1.75; P=.03). Patients with a PSA level >0.1ng/mL after neoAS and before the start of RT had less favorable clinical outcomes than patients whose PSA level was ≤0.1ng/mL. The role of post-neoAS, pre-RT PSA level relative to PSA levels obtained along the continuum of medical care is not presently defined but could be tested in future clinical trials.

Salvage radiotherapy for biochemical recurrence after radical prostatectomy: experience of a single center

Background: The purpose of this study was to report the outcomes and prognostic factors of patients who underwent salvage radiotherapy (SRT) for biochemical recurrence (BCR) following radical prostatectomy (RP) at a single center. Methods: We retrospectively reviewed 48 patients who underwent SRT for BCR after RP between January 2004 and December 2012. The Kaplan-Meier method and Cox proportional hazard regression models were used to evaluate the BCR-free survivals and the prognostic factors for BCR after SRT. Results: After a median follow-up of 68.7 months (range, 34.0–143.3 months). The BCR-free survival rates at 3 and 5 years for the 48 patients after SRT were 72.9% and 68.4%, respectively. Multivariate analysis showed that pre-RT PSA (prostate specific antigen) level >0.5 ng/mL, Gleason score at RP ≥8, and seminal vesicle invasion were significantly predictive of PSA relapse after SRT (HR: 23.29, 7.92, and 21.73). The BCR-free rate at 5 years in the pre-RT PSA level ≤0.5 and >0.5 ng/mL group was 83.4% and 52.2% (P=0.007), respectively. No grade 3 or worse acute adverse events were noted. Conclusions: SRT was an effective treatment for BCR following RP with tolerable toxicities. Lower pre-RT PSA value, low Gleason score, and non-seminal vesicle invasion were significant predictors of favorable biochemical outcomes. Our results supported the current recommendations that SRT should be initiated before PSA reaches 0.5 ng/mL.

Outcomes and toxicity of 313 prostate cancer patients receiving helical tomotherapy after radical prostatectomy

PurposeThere are limited long-term data on patients treated with image guided intensity modulated radiation therapy (IG-IMRT) for prostate cancer recurrence or high-risk disease features after radical prostatectomy. We report single-institution results for patients treated with IG-IMRT and identify variables associated with outcome. Methods and materialsThis is a retrospective chart review consisting of 313 consecutive patients who were treated with adjuvant or salvage IG-IMRT from 2004 to 2013. Cox proportional hazards analysis was used to identify factors related to survival and toxicity. Toxicity was graded using the Common Terminology Criteria for Adverse Events Version 4.0. ResultsThe median follow-up was 55 months (range, 6-131 months). The median pre-radiation therapy (RT) prostate-specific antigen (PSA) was 0.3 ng/mL (range, <0.01-55.4). The vast majority of patients (87%) received elective pelvic nodal irradiation (median dose: 45 Gy). Androgen deprivation therapy (ADT) was given to 39% of patients for a median of 9 months. Five-year biochemical progression-free survival and distant metastasis-free survival were 59% (95% confidence interval, 53%-66%) and 89% (95% confidence interval, 85%-93%), respectively. On multivariate analysis, higher pre-RT PSA (>0.2 ng/mL), biopsy Gleason score (≥7 [4+3]), and duration of ADT (>6 months) were significantly associated (P < .05) with biochemical progression-free survival. Actuarial late grade 3 genitourinary and gastrointestinal toxicities at 5 years were 10% and 2%, respectively. ConclusionOur results suggest that lower pre-RT PSA level and longer duration of ADT are associated with improved biochemical control. The incidence of late grade 3 gastrointestinal toxicity was low, but late grade 3 genitourinary toxicity was higher than anticipated.

Validation of a genomic classifier for prediction of metastasis following postoperative salvage radiation therapy.

4 Background: Management of patients with a postoperative rising prostate-specific antigen (PSA) level is complex. Additional local treatment such as salvage radiation therapy (SRT) may be sufficient for many patients but some may require concurrent systemic therapy in order to delay or prevent metastatic disease. As PSA recurrence on its own is a poor surrogate for metastatic disease we hypothesized that the Decipher genomic classifier (GC), a validated predictor of metastasis may be able to better distinguish those patients where additional therapy is beneficial from those where SRT on its own is likely sufficient. Methods: Genomic classifier (GC) scores were calculated from 170 prostate cancer patients, who received SRT at the Veteran Affairs Medical Center Durham, Thomas Jefferson University and Mayo Clinic, between 1990 and 2010. SRT was defined as administration of RT with Pre-RT PSA levels &gt; 0.2 ng/ml. GC and CAPRA-S scores were compared using survival c-index, competing-risks and Cox regression analysis for the prediction of metastasis. Results: Survival c-index for predicting metastasis 5 years post SRT was 0.85 (95% CI: 0.73-0.88) for GC and 0.63 (95% CI: 0.49-0.77) for CAPRA-S. The cumulative incidence of metastasis at 5 years post-SRT was 2.7%, 8.4%, and 33.1% for low, average, and high GC scores (p &lt; 0.001) and 16.9%, 2.3% and 17.2% for low, average and high CAPRA-S scores (p = 0.113). In univariable analysis only GC, extraprostatic extension, path GS and Pre-RT PSA were significant predictors of metastasis. In multivariable analyses with clinical risk factors or the CAPRA-S risk model, GC was the only independent predictor of metastasis with a HR of 1.63 (1.22-2.18, p &lt; 0.001) for a 10% unit increase in risk score. Conclusions: In patients treated with postoperative SRT for PSA recurrence, GC is a powerful predictor of metastasis. Patients with low Decipher have excellent prognosis with SRT and may avoid concurrent hormonal therapy. Patients with high Decipher risk are at highest risk for metastatic disease and SRT failure and may benefit from intensified systemic therapy.

Pre-radiotherapy PSA Level as a Predictor for Biochemical Control in Prostate Cancer Patients Receiving Radiotherapy after Radical Prostatectomy

To report the outcome of patients receiving radiotherapy (RT) after radical prostatectomy (RP). Between May 2001 and December 2008, 53 consecutive cases of prostate adenocarcinoma treated with RP and RT were reviewed. A total of 49 patients were eligible for this study. After a median follow-up of 53 months, the 4-year overall survival (OS) and biochemical progression-free survival (bPFS) for all patients were 91.0% and 68.9%, respectively. According to univariate and multivariate analysis, pre-RT prostate-specific antigen (PSA) was the most significant factor for bPFS. Patients with pre-RT PSA levels of < 0.2 ng/ml and ≧ 0.2 ng/ml had a 4-year bPFS of 83.1% and 52.6%, respectively (p = 0.013). The incidence of chronic rectal toxicity was low, with no grade 3 toxicity reported and grade 2 toxicity found in only 6 patients (12.2%). However, long-term urinary toxicity of grade 2 or higher was found in 24 patients (49.0%). For patients with increasing PSA levels following RP, local RT should be administered prior to biochemical failure (PSA ≧ 0.2), to ensure good bPFS.

Detection of local recurrent prostate cancer after radical prostatectomy in terms of salvage radiotherapy using dynamic contrast enhanced-MRI without endorectal coil

PurposeTo evaluate the value of dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) without endorectal coil (EC) in the detection of local recurrent prostate cancer (PC) after radical prostatectomy (RP).Material and methodsThirty-three patients with recurrent PC underwent DCE-MRI without EC before salvage radiotherapy (RT). At median 15 (mean 16±4.9, range 12–27) months after completion of RT all patients showed complete biochemical response. Additional follow up post RT DCE-MRI scans were available. Prostate specific antigen (PSA) levels at the time of imaging were correlated to the imaging findings.ResultsIn 22/33 patients (67%) early contrast enhancing nodules were detected in the post-prostatectomy fossa on pre-RT DCE-MRI images. The average pre-RT PSA level of the 22 patients with positive pre-RT DCE-MRI findings was significantly higher (mean, 0.74±0.64 ng/mL) compared to the pre-RT PSA level of the 11 patients with negative pre-RT DCE-MRI (mean, 0.24±0.13 ng/mL) (p<0.001). All post-RT DCE-MRI images showed complete resolution of initial suspicious lesions. A pre-RT PSA cut-off value of ≥0.54 ng/ml readily predicted a positive DCE-MRI finding.ConclusionsThis is the first study that shows that DCE-MRI without EC can detect local recurrent PC with an estimated accuracy of 83% at low PSA levels. All false negative DCE-MRI scans were detected using a PSA cut-off of ≥0.54 ng/mL.

PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs ≥0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level≥0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level≥0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.

Early salvage radiotherapy for patients with PSA relapse after radical prostatectomy

To assess the effectiveness of early salvage radiotherapy (RT) for patients with prostate-specific antigen (PSA) relapse after radical prostatectomy (RP) retrospectively. Fifty-one patients underwent salvage RT for biochemical relapse of prostate cancer initially treated with RP. All patients had persistent or rising PSA >0.20 ng/ml at some point after surgery, or three successive PSA elevations after a postoperative nadir if PSA was < or =0.20 ng/ml. Most (96%) of pre-RT PSA were less or equal to 0.50 ng/ml, and median value was 0.25 ng/ml (range, 0.05-0.90 ng/ml). Median RT dose was 60 Gy (range, 50-66 Gy). Multivariate Cox regression analysis was performed for PSA before RP and salvage RT, margin status, seminal vesicle involvement, extracapsular invasion, Gleason score, PSA doubling time (PSADT), and RT dose to identify significant predictors of biochemical outcome. Median follow-up was 36 months. The 3-year biochemical no evidence of disease rate (bNED) was 55.1%. On multivariate analysis only the following factors were significantly associated with improved bNED: PSADT >3.0 months (P = 0.008), Gleason score < or =7 (P = 0.01), and RT dose > or =60 Gy (P = 0.028). Although a total dose of 60 Gy was effective at a low pre-RT PSA levels with short follow-up, an RT dose > or =60 Gy resulted in superior biochemical outcomes even in patients with a pre-RT PSA < or =0.50 ng/ml.

Obesity and Risk of Biochemical Failure for Patients Receiving Salvage Radiotherapy After Prostatectomy

Obesity has been proposed as an independent risk factor for patients undergoing surgery or radiotherapy (RT) for prostate cancer. Using body mass index (BMI) as a measure of obesity, we tested its role as a risk factor for patients receiving salvage RT after prostatectomy. Rates of subsequent biochemical relapse were examined in 90 patients who underwent salvage RT between 1984 and 2004 for biochemical failure after radical prostatectomy. Median follow-up was 3.7 years. The BMI was tested as a continuous and categorical variable (stratified as <25, 25-<30, and >or=30 kg/m(2)). Univariate and multivariate proportional hazards regression analyses were performed for clinical, pathologic, and treatment factors associated with time to relapse after salvage RT. There were 40 biochemical failures after salvage RT with a median time to failure of 1.2 years. The BMI was not associated with adverse clinical, pathologic, or treatment factors. On multivariate analysis, obesity was independently significant (hazard ratio [HR], 1.2; p = 0.01), along with RT dose (HR, 0.7; p = 0.003) and pre-RT prostate-specific antigen level (HR, 1.2; p = 0.0003). This study is weakly suggestive that obesity may be a risk factor for salvage RT patients. Whether this results from greater biologic aggressiveness or technical inadequacies cannot be answered by this study. Given the very high failure rate observed for severely obese patients, we propose that technical difficulties with RT are at play. This hypothesis is supported by the RT literature and could be prospectively investigated. Techniques that optimize targeting, especially in obese patients, perhaps seem warranted at this time.

Salvage Radiotherapy After Postprostatectomy Biochemical Failure: Does Pretreatment Radioimmunoscintigraphy Help Select Patients with Locally Confined Disease?

Radioimmunoscintigraphy (RIS) has the potential to demonstrate early recurrences after prostatectomy and might be useful in selecting patients for salvage radiotherapy (RT). A total of 82 patients with adenocarcinoma of the prostate were treated with salvage RT between 1988 and 2005, for an elevated prostate-specific antigen (PSA) level after prostatectomy. Of the 82 patients, 32% had Gleason score 6 or less disease, 54% Gleason score 7 disease, 70% had Stage pT3 disease, 55% had positive margins, and 5% had pathologic lymph node involvement. The median pre-RT PSA level was 0.63 ng/mL. Of the 82 patients, 47 (57%) had a pre-RT RIS (ProstaScint) scan, which was used for both patient selection and target delineation. The RT regimen was a median dose of 66 Gy to the prostate bed. Also, 64% received androgen deprivation therapy. Biochemical failure was defined as a PSA level >0.1 ng/mL and increasing. Patients with a pre-RT RIS scan had a lower preoperative PSA level (p = 0.0240) and shorter follow-up (p = 0.0221) than those without RIS. With a median follow-up of 44 months, the biochemical control rate was 56% at 3 years and 48% at 5 years. Margin status was the only factor associated with biochemical control on univariate (p = 0.0055) and multivariate (p = 0.0044) analysis. Patients who had prostate bed-only uptake on RIS (n = 38) did not have improved outcomes, with biochemical control rates of 51% at 3 years and 40% at 5 years. Patients treated with salvage RT had modest responses. Patients who were selected for treatment with RIS did not have better biochemical outcomes. Our results indicated that patients with positive margins were most likely to benefit from salvage RT.

Predicting PSA failure following salvage radiotherapy for a rising PSA post-prostatectomy: From the CaPSURE™ database

Background The role of radiotherapy (RT) for rising PSA after radical prostatectomy (RP) is debatable. We analyzed a large database of men to evaluate for predictors of prostate-specific antigen (PSA) failure after salvage RT. Methods Data from the Cancer of the Prostate Strategic Urologic Research Endeavor database (CaPSURE™) identified 4,563 men with RP between 1989 and 2004; 194 underwent salvage RT ≥6 months after RP. PSA failure following RT was defined as a PSA >0.2 ng/ml. The association between clinical and pathologic characteristics and PSA failure was examined using a χ-square metric. A multivariable analysis of predictors for time to PSA failure was performed using a Cox proportional hazard regression model. Results After a median follow-up of 66 months, 121 (62%) men experienced PSA failure at a median 20 months. Significant associations for PSA failure were found for the clinical T category ( P < .01), race/ethnicity ( P = 0.04), pT3 disease ( P < 0.01), seminal vesicle invasion ( P < 0.01), and pre-RT PSA level ( P < 0.01). The pre-RT PSA level ( P = 0.07) was the only factor to approach significance as an independent predictor of PSA failure on multivariable analysis. Pre-RT PSA doubling time was calculated for 131 men but did not predict for PSA failure on univariate ( P = 0.38) or multivariate analyses ( P = 0.13) for ≤12 vs. >12 months. Conclusions Salvage RT provided the greatest benefit in PSA control in men with the lowest pre-RT PSA levels. Post-RP PSA doubling time >12 months trended toward predicting for PSA failure but was not significant likely owing to limited sample size. Together, these findings would suggest that salvage RT is optimal at low pre-RT PSA and long doubling times with favorable pathologic features.

Postoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy

Identification of patients most likely to benefit from salvage radiotherapy (RT) using postoperative (postop) prostate-specific antigen (PSA) kinetics. From 1984 to 2004, 81 patients who fit the following criteria formed the study population: undetectable PSA after radical prostatectomy (RP); pathologically negative nodes; biochemical relapse defined as a persistently detectable PSA; salvage RT; and two or more postop PSAs available before salvage RT. Salvage RT included the whole pelvic nodes in 55 patients and 4 months of total androgen suppression in 56 patients. The median follow-up was >5 years. All relapses were defined as a persistently detectable PSA. Kaplan-Meier and Cox proportional hazards multivariable analysis were performed for all clinical, pathological, and treatment factors predicting for biochemical relapse-free survival (bRFS). There were 37 biochemical relapses observed after salvage RT. The 5-year bRFS after salvage RT for patients with postop prostate-specific antigen velocity < or = 1 vs. >1 ng/ml/yr was 59% vs. 29%, p = 0.002. In multivariate analysis, only postop PSAV (p = 0.0036), pre-RT PSA level < or = 1 (p = 0.037) and interval-to-relapse >10 months (p = 0.012) remained significant, whereas pelvic RT, hormone therapy, and RT dose showed a trend (p = approximately 0.06). PSAV, but not prostate-specific antigen doubling time, predicted successful salvage RT, suggesting an association of zero-order kinetics with locally recurrent disease. Postoperative PSA velocity independently predicts for the failure of salvage RT and can be considered in addition to high-risk features when selecting patients in need of systemic therapy following biochemical failure after RP. For well-selected patients, salvage RT can achieve high cure rates.

Long-term follow-up of 111In-capromab pendetide (ProstaScint) scan as pretreatment assessment in patients who undergo salvage radiotherapy for rising prostate-specific antigen after radical prostatectomy for prostate cancer

To evaluate the long-term failure patterns in patients who underwent an (111)In-capromab pendetide (ProstaScint) scan as part of their pretreatment assessment for a rising prostate-specific antigen (PSA) level after prostatectomy and subsequently received local radiotherapy (RT) to the prostate bed. Fifty-eight patients were referred for evaluation of a rising PSA level after radical prostatectomy. All patients had negative findings for metastatic disease after abdominal/pelvis imaging with CT and isotope bone scans. All patients underwent a capromab pendetide scan, and the sites of uptake were noted. All patients were treated with local prostate bed RT (median dose 66.6 Gy). Of the 58 patients, 20 had biochemical failure (post-RT PSA level >0.2 ng/mL or a rise to greater than the nadir PSA), including 6 patients with positive uptake outside the bed (positive elsewhere). The 4-year biochemical relapse-free survival (bRFS) rates for patients with negative (53%), positive in the prostate bed alone (45%), or positive elsewhere (74%) scan findings did not differ significantly (p = 0.51). The positive predictive value of the capromab pendetide scan in detecting disease outside the bed was 27%. The capromab pendetide scan status had no effect on bRFS. Those with a pre-RT PSA level of <1 ng/mL had improved bRFS (p = 0.003). The capromab pendetide scan has a low positive predictive value in patients with positive elsewhere uptake and the 4-year bRFS was similar to that for those who did not exhibit positive elsewhere uptake. Therefore, patients with a postprostatectomy rising PSA level should considered for local RT on the basis of clinicopathologic factors.

Long-Term Results and Predictive Factors of Three-Dimensional Conformal Salvage Radiotherapy for Biochemical Relapse After Prostatectomy

Salvage radiotherapy (RT) is used to treat patients with biochemical failure after radical prostatectomy (RP). Although retrospective series have demonstrated that salvage RT will result in biochemical response in approximately 75% of patients, long-term response is much lower (20-40%). The purpose of this study was to determine prognostic factors related to the prostate-specific antigen (PSA) outcome after salvage RT. Between 1991 and 2004, 171 patients received salvage RT at the University of Heidelberg. Patient age, margin status, Gleason score, tumor grading, pathologic tumor stage, pre-RP and pre-RT PSA levels, and time from RP to rise of PSA were analyzed. Median follow-up time was 39 months. The 5-year overall and clinical relapse-free survival were 93.8% and 80.8%, respectively. After RT serum PSA decreased in 141 patients (82.5%). The 5-year biochemical relapse-free survival was 35.1%. Univariate analysis showed following statistically significant predictors of PSA recurrence after RT: preoperative PSA level (p = 0.035), pathologic tumor classification (p = 0.001), Gleason score (p < 0.001), tumor grading (p = 0.004), and pre-RT PSA level (p = 0.031). On multivariate analysis, only Gleason score (p = 0.047) and pre-RT PSA level (p = 0.049) were found to be independently predictive of PSA recurrence. This study represents one of the largest retrospective studies analyzing the outcome of patients treated with salvage RT at a single institution. Our findings suggest that patients with Gleason score <7 and low pre-RT PSA levels are the best candidates for salvage RT, whereas patients with high-grade lesions should be considered for additional treatment (e.g., hormonal therapy).

Postoperative Radiotherapy for Patients with Prostate Cancer in Japan; Changing Trends in National Practice between 1996–98 and 1999–2001: Patterns of Care Study for Prostate Cancer

To evaluate the changing trends of standards and practices for postoperative radiotherapy (RT) for patients with prostate cancer in Japan. The Japanese Patterns of Care Study (PCS) conducted a national survey in 84 institutions from 1996 to 1998 (PCS96-98) and 76 institutions from 1999 to 2001 (PCS99-01). Detailed information relevant to RT was collected on a total of 169 patients (64 from 1996 to 1998 and 105 from 1999 to 2001) with prostate cancer who had undergone radical prostatectomy. The fraction of clinical T3-4 tumours before prostatectomy decreased from 63% in the period 1996-98 to 26% in the period 1999-2001 (P = 0.0004). The pre-RT prostate-specific antigen level was significantly lower in 1999-2001 than in 1996-98 (P = 0.0002). We did not find a significant difference in the percentage of patients who received pelvic irradiation in the time periods between PCS96-98 and PCS99-01 (P = 0.18). Although the median radiation doses of 60 Gy were not changed between the surveys, various doses (from 20 to 74.6 Gy) were delivered to the prostatic bed. In the 1999-2001 survey, 73 of 105 patients received a median dose of 56 Gy in an adjuvant setting, while the other 32 received a median dose of 60 Gy in a salvage setting (P = 0.0015). These data suggest that consensus has not been reached on the practice and management of postoperative RT for patients with prostate cancer in Japan.

Parameters for Treatment Decisions for Salvage Radiation Therapy

Radical prostatectomy (RP) is the most common primary treatment for prostate cancer. About 40% of those with high-risk pathologic features, such as a positive margin or seminal vesicle involvement, will develop biochemical failure at some point in the future. Radiotherapy (RT), with or without concurrent androgen deprivation, has been used liberally in the management of men with a rising prostate-specific antigen (PSA) after RP, based mostly on relatively small retrospective series. Factors such as the prostatectomy Gleason score, seminal vesicle invasion, absolute pre-RT PSA level, and pre-RT PSA doubling time are emerging as important determinants of outcome after RT. These factors should be used as a guide to the options of local therapy alone (RT), local therapy plus systemic therapy (typically androgen deprivation therapy), and systemic therapy alone.

Comparison of adjuvant versus salvage radiotherapy policies for postprostatectomy radiotherapy

Purpose We compared the long-term results of postprostatectomy radiotherapy (RT) from two institutions, one adapting a prospective policy of adjuvant RT and the other salvage RT. Methods and materials Between 1989 and 1997, 69 patients were referred for adjuvant RT to the institution using adjuvant RT and 88 patients with evidence of recurrence were treated in the institution using salvage RT. The salvage group underwent RT after longer postoperative intervals (median, 40.3 vs. 2.9 months; p <0.0001) and had higher prostate-specific antigen (PSA) values before starting RT (4.5 vs. 0.86 ng/mL; p = 0.003). Both groups were routinely treated to a minimal total dose of 60 Gy. The treatment groups were analyzed for overall survival, disease-specific survival, distant metastasis-free survival, and biochemical recurrence-free survival (BRFS) using Cox proportional hazards modeling. Results Of the 69 patients referred for adjuvant RT, 22 (32%) had nonzero PSA values before RT. Multivariable modeling of BRFS found only the PSA value before RT to be statistically significant ( p <0.0001). RT after prostatectomy was equally effective in either setting when the pre-RT PSA level was <1 ng/mL. When the PSA value before RT was ≥1 ng/mL, the 5-year BRFS for each group was inferior. Conclusion Although the adjuvant treatment policy was associated with significantly improved BRFS, this was attributable to low pre-RT PSA values. When the treatment groups were stratified for pre-RT PSA level, the differences in BRFS were not statistically significant. Patients with a rising PSA level after prostatectomy, regardless of their initial risk, should receive prompt referral for RT.

Salvage radiotherapy for biochemical recurrence after radical prostatectomy: a study of 62 patients

ObjectivesTo determine the predictive factors of prostate-specific antigen (PSA) recurrence after salvage radiotherapy (RT) for biochemical recurrence following radical prostatectomy (RP) to identify patients who may benefit from this treatment. MethodsFrom June 1992 to January 2002, 62 patients experiencing PSA recurrence after RP were treated with RT at a dose of 65 Gy. No patient received hormonal therapy. PSA recurrence after RT was defined as three consecutive increased PSA measurements. The risk of experiencing PSA recurrence after RT was analyzed according to 10 factors: patient age, pre-RP PSA level, pathologic stage, Gleason score, surgical margin status, PSA nadir after RP, time to PSA recurrence after RP, pre-RT PSA level, PSA nadir after RT, and length of follow-up after RT. ResultsWith a mean follow-up of 44 months (range 3 to 110), 23 patients (37.1%) experienced PSA recurrence after RT. Using univariate analysis, six factors were found to be predictive of PSA recurrence after RT: the length of follow-up after RT (P <0.0001), PSA nadir after RP (P = 0.0004), time to PSA recurrence after RP (P = 0.003), pre-RP PSA level (P = 0.008), Gleason score (P = 0.011), and pre-RT PSA level (P = 0.028). Using multivariate analysis, only the Gleason score (P = 0.015) and length of follow-up after RT (P = 0.02) were found to be predictive of PSA recurrence after RT. A Gleason score greater than 7 was a significant predictor of PSA recurrence after salvage RT (P = 0.04). ConclusionsIn our experience, the Gleason score and length of follow-up were the sole independent predictors of PSA recurrence after salvage RT. Our findings suggest that patients with a Gleason score of 7 or less are more likely to benefit from salvage RT after RP and that the durability of the PSA response may be only transient.