Prostate-specific Antigen Bounce Research Articles

Focal Boosted IMRT Treatment of Prostate Cancer to 84 Gy in 28 Fractions: Preliminary Clinical Outcomes and Dosimetry

The FLAME trial reported that focal boosting of prostate tumor to 95 Gy in 35 fractions improves biochemical control. However, this treatment is not commonly used in the United States. We investigated a focally boosted treatment of 84 Gy in 28 fractions (EQD2 108 Gy, BED 252 Gy). Between 2019-2022, men with unfavorable intermediate risk (uIR) and high risk (HR) prostate cancer were enrolled on a prospective registry and received a novel IMRT regimen. The dose levels were 84 Gy to the gross tumor volume (GTV) as defined on mpMRI (T2W and ADC) with no added margin, 70 Gy to the prostate and proximal seminal vesicles, and optional 50.4 Gy to elective pelvic lymph nodes (all 28 fractions). Patients received fiducial markers and hydrogel spacer. The treatment planning goal was to cover 95% of the GTV at 84 Gy, and also meet the target and normal tissue dosimetry criteria of the hypofractionated treatment arm of NRG-GU005. VMAT was used for treatment delivery. ADT was given at the discretion of the treating physician. A total of 20 men were included in the study, 2 (10%) uIR and 18 (90%) HR. 9 (45%) tumors were GS 7, 7 (35%) were GS 8, and 4 (20%) were GS 9. There were 13 (65%) stage cT1, 4 (20%) cT2 and 3 (15%) cT3. One (5%) patient received short term ADT, 18 (95%) long term ADT, and 1 (5%) refused ADT. 18 (90%) men received elective nodal radiation. The mean baseline PSA was 25.1 (range 4.2-73.4). The median baseline IPSS score was 11.1 (IQR 4.5-12), and 4 patients had severe baseline urinary symptoms (IPSS ≥20). The mean baseline prostate volume was 57.4 cc (range 26.8-198.3). The mean volume of the 84 Gy boost target was 7.1 cc (range 2.3-15.0) and the mean proportion of the prostate boosted was 14.8% (range 2% - 47%). There were 10 (50%) men with 1 boost target, 6 (30%) with two, 3 (15%) with three, and 1 (5%) had 4 boost targets. Targets were located in peripheral zone (85%), transition zone (30%), and central zone (5%). Patients met all per-protocol normal tissue criteria of NRG-GU005, except for bladder D0.03cc. The mean±SD (Gy) rectum D15%, D25%, and D30% were 51±5, 45±5, 42±4. The mean±SD (Gy) bladder D0.03cc, D30%, D50% were 79±4, 50±8, 38±10. At a median follow up time of 21.3 months (range 7.1-38.2), no patients have developed biochemical progression, local recurrence, distant progression, or death from prostate cancer. One patient died at 18 months from metastatic colorectal cancer, unrelated to prostate cancer treatment. Acute grade 1-2 GU toxicity occurred in 13 (65%) patients, and acute grade 1-2 GI toxicity occurred in 4 (20%) patients. No patients developed grade 3+ acute or late GU or GI toxicity. Two patients required temporary foley catheter for obstruction during RT, and both had IPSS >20 at baseline. The patient who refused ADT had a PSA bounce of magnitude 2.2 ng/mL at 14 months, PSA values declined without additional treatment. A novel 28-fraction focal boosted IMRT treatment is feasible and has an acceptable early toxicity profile. Oncologic results are promising but require longer follow up.

Prostate-Specific Antigen Bounce after 125I Brachytherapy Using Stranded Seeds with Intraoperative Optimization for Prostate Cancer.

Simple SummaryOur study investigated clinical features of prostate-specific antigen (PSA) bounce in patients undergoing brachytherapy. PSA bounce is common and discriminating between large bounces and biochemical failures is very difficult. Therefore, we suggest important points to discriminate between large bounces and biochemical failures. In addition, we aimed to examine the clinical features and details of PSA bounce in patients receiving brachytherapy.Prostate-specific antigen (PSA) bounce is common in patients undergoing 125I brachytherapy (BT), and our study investigated its clinical features. A total of 100 patients who underwent BT were analyzed. PSA bounce and large bounce were defined as an increase of ≥0.2 and ≥2.0 ng/mL above the initial PSA nadir, respectively, with a subsequent decline without treatment. Biochemical failure was defined using the Phoenix definition (nadir +2 ng/mL), except for a large bounce. With a median follow-up of 49 months, 45% and 7% of the patients experienced bounce and large bounce, respectively. The median time to bounce was 24 months, and the median PSA value at the bounce spike was 1.62 ng/mL, a median raise of 0.44 ng/mL compared to the pre-bounce nadir. The median time to bounce recovery was 4 months. The post-bounce nadir was obtained at a median of 36 months after low-dose-rate BT. On univariate analysis, age, the PSA nadir value at 2 years, and prostate volume were significant factors for PSA bounce. The PSA nadir value at 2 years remained significant in multivariate analysis. We should carefully monitor young patients with high prostate volume having a >0.5 PSA nadir value at 2 years for PSA bounce.

PD22-09 DISTINGUISHING BETWEEN PROSTATE SPECIFIC ANTIGEN BOUNCE AND BIOCHEMICAL RECURRENCE FOLLOWING STEREOTACTIC BODY RADIOTHERAPY FOR PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022PD22-09 DISTINGUISHING BETWEEN PROSTATE SPECIFIC ANTIGEN BOUNCE AND BIOCHEMICAL RECURRENCE FOLLOWING STEREOTACTIC BODY RADIOTHERAPY FOR PROSTATE CANCER Ashley Monaco, Jessica Sommer, Jordan Mendelson, Jonathan Haas, Anthony Corcoran, and Aaron Katz Ashley MonacoAshley Monaco More articles by this author , Jessica SommerJessica Sommer More articles by this author , Jordan MendelsonJordan Mendelson More articles by this author , Jonathan HaasJonathan Haas More articles by this author , Anthony CorcoranAnthony Corcoran More articles by this author , and Aaron KatzAaron Katz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002564.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While prostate specific antigen (PSA) bounce following radiation therapy for prostate cancer (PCa) treatment is well established, the parameters to predict this occurrence and differentiate it from biochemical recurrence (BCR) following stereotactic body radiotherapy (SBRT) are unknown. The purpose of this study is to investigate associations between pre-treatment and post-treatment variables among patients experiencing PSA bounce, BCR, or neither following SBRT. METHODS: An IRB-approved PCa database was reviewed for patients who underwent primary SBRT. Patients with less than 18 months of follow-up or were missing >3 PSA measurements following SBRT were excluded. Patients were divided into outcome groups experiencing PSA bounce, BCR, or neither. PSA bounce was defined as a rise of >0.2 ng/mL over the pre-rise nadir followed by a decline without intervention. BCR was defined by Phoenix criteria. Pre-treatment and post-treatment characteristics were analyzed between groups. Results that were significant when comparing PSA bounce to BCR were then analyzed in a multivariate logistic regression model to determine predictors for PSA bounce. RESULTS: We analyzed 170 men with a median age of 72 (52-87) years with an average follow-up time of 75 + 21 months, of which 28 (16%) experienced PSA bounce and 42 (25%) had BCR (Table 1). Pre-treatment D’Amico and Capra risk, Gleason group, PSA, prostate volume, prostate density and post-treatment PSA velocity were not associated with PSA bounce when compared to BCR or non-BCR/bounce cohorts. Compared to those who did not experience PSA bounce/BCR, those with PSA bounce were younger (p <.05), had lower PSA doubling time (p <.001), and took longer to reach PSA nadir (p <.001). Compared to BCR group, men with PSA bounce had lower PSA nadir and took longer to reach nadir, both of which were significant predictors for PSA bounce (OR: 4.3, p <.05; OR: 0.90, p <.001). PSA bounce occurred significantly earlier than BCR (16 vs. 33 months; p <.001). CONCLUSIONS: While there is overlap among patients who experience PSA bounce or BCR following SBRT, the timing of which the PSA rise occurs, the PSA nadir value, and the time to PSA nadir are useful variables in the management of a rising PSA in patients following SBRT. Source of Funding: Department of Urology, NYU Langone Hospital – Long Island © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e407 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ashley Monaco More articles by this author Jessica Sommer More articles by this author Jordan Mendelson More articles by this author Jonathan Haas More articles by this author Anthony Corcoran More articles by this author Aaron Katz More articles by this author Expand All Advertisement PDF DownloadLoading ...

Prostate-specific antigen kinetics and metastasis-free survival in patients treated with external beam radiotherapy combined with high-dose-rate brachytherapy boost and androgen deprivation therapy for localized prostate cancer.

PurposeSerum prostate-specific antigen (PSA) kinetics has been linked to prognosis in prostate cancer (PCa) patients. Our goal was to analyze the association between PSA kinetics and metastasis-free survival (MFS) in patients with localized PCa treated with high-dose-rate (HDR) brachytherapy (BT) boost combined with external beam radiotherapy (EBRT).Material and methodsWe retrospectively analyzed multiple PSA kinetics related to PSA nadir (nPSA), PSA bouncing, and biochemical recurrence (BCR) in 186 PCa patients treated with neoadjuvant androgen deprivation therapy (ADT), followed by EBRT combined with HDR-BT boost. Uni- and multivariate Cox regression models were calculated to assess the value of PSA-related parameters for the prediction of MFS.Results5- and 10-year MFS were 95% and 84%, respectively. Median nPSA was 0.011 (IQR, 0.007-0.057) ng/ml and predicted MFS in multivariable analysis. Implementation of nPSA improved c-index of baseline model from 0.8 to 0.68. nPSA of 0.2 ng/ml offered the most optimal discriminatory ability for identifying patients with better prognoses. Time to nPSA (median, 11 months; IQR, 8-18 months) and PSA bounce, which occurred in 12.4% of patients, were not significantly associated with MFS.ConclusionsLower values of nPSA are significantly associated with decreased risk of developing metastases in patients treated with EBRT combined with HDR-BT boost and ADT, and improve the accuracy of a clinical model for MFS.

Prognostic value of PSA bounce after definitive radiotherapy revisited.

Prostate-specific antigen (PSA) bounce after definitive radiotherapy has been reported as a predictor of improved biochemical recurrence-free survival (BCRFS). We revisited this phenomenon to confirm its clinical impact on oncological outcomes in patients with long-term follow-up who were free of biochemical recurrence (BCR) at least 3years after treatment. A total of 541 patients with localized, intermediate-risk prostate cancer underwent low-dose rate brachytherapy with iodine-125 seeds with or without supplemental external beam radiotherapy in combination. Neoadjuvant hormonal therapy was administered to 273 patients (50.5%) with a median duration of 3months (range 1-108months). PSA bounce was defined as ≥ 0.2ng/ml increase above the interval PSA nadir, followed by a decrease below that value. The median age was 69years (range 49-90years). The median follow-up duration was 102months (range 36-205months). One-hundred and fifty patients (27.7%) had PSA bounce with a median magnitude of 0.47ng/ml (range 0.2-3.19ng/ml). Age was significantly associated with the occurrence of PSA bounce [age: hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.93-0.98]. It was found to be independently associated with a decreased risk for BCR (HR 0.29; 95% CI 0.12-0.69) and clinical progression (HR 0.44; 95% CI 0.95-0.98). PSA bounce indicated a favorable BCRFS and clinical progression-free survival in patients who had been free of BCR for at least 3years after definitive radiotherapy.

Working Towards a New Definition of Biochemical Failure in the Era of Stereotactic Body Radiation Therapy for Prostate Cancer

Since the seminal Phoenix definition (nadir PSA+2) of biochemical failure (BCF) was published in 2006, increasingly more patients with low- and intermediate-risk prostate cancer (PCa) are being treated with stereotactic body radiation therapy (SBRT). Since SBRT leads to lower nadir PSA (nPSA) compared to conventionally fractionated RT, we investigated if an earlier nPSA+threshold can be used as an alternative definition of BCF.PSA kinetics from 9 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2003 to 2018. Patients received 35 to 40 Gy in 5 fractions, 38 Gy in 4 fractions or 26 Gy in 2 fractions (EQD23 Gy = 70-95 Gy) per institutional standards. Cox multivariable regression model was used to determine the adjusted association of relative change in PSA kinetics with biochemical relapse-free survival (BRFS) and association of BCF with time to nadir+2.A total of 2061 patients were included. Median follow-up was 71.9 months (interquartile range [IQR], 41.2-96.0). BCF occurred in 140 (6.8%) of patients. Median nPSA was 0.16 ng/mL, median time to nPSA was 48 months. Sensitivity of Phoenix definition for BCF was 93%, compared to 96%, 100%, and 100% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. False positive rate of Phoenix definition was 30%, compared to 41%, 58%, and 71% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. In patients who developed BCF, lead time gained from an earlier nPSA+threshold definition compared to Phoenix definition was 6 (IQR 0-15.3), 0 (IQR 0-11.3), 0 (IQR 0-0) months for nPSA+0.5, nPSA+1.0 and nPSA+1.5, respectively. Relative change in PSA between 6 months and 18 months after treatment was significantly associated with BRFS (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.28-2.34, P < 0.0004). Among the 30% patients who had a false call of BCF due to PSA bounce, 48 (84.2%) reached nPSA+2 in ≤18 months, and 9 (15.8%) in > 18 months. In patients who had BCF, 27 (19.3%) reached nPSA+2 in ≤18 months, and 113 (80.7%) in > 18 months. Median time to nPSA+2 was significantly longer in patients with BCF (41 vs. 12 months, P < 0.002). BCF is associated with longer time to nPSA+2 (HR 0.13, 95% CI 0.09-0.20, P < 0.002).A lower nadir-based threshold provides minimal increase in sensitivity at the cost of a higher false positive rate and does not provide a clinically relevant lead time benefit for a pending BCF in patients with low- to intermediate-risk PCa undergoing SBRT. A rate-of-change based metric in the first 18 months post-SBRT is significantly associated with BRFS. Patients who have an early PSA bounce after SBRT rarely develop a true BCF and true BCF tends to happen later (> 18 months). Phoenix definition remains a valuable tool in the SBRT era. BCF should not be prematurely called which runs the risk of high rates of false positivity.

Early Prostate-Specific Antigen Kinetics for Low- and Intermediate-Risk Prostate Cancer Treated With Definitive Radiation Therapy

PurposeThis study used a patient-specific model to characterize and compare ideal prostate-specific antigen (PSA) kinetics for low- and intermediate-risk prostate cancer after definitive radiation treatment with conventionally fractionated, hypofractionated, stereotactic body radiation therapy, or brachytherapy, both high-dose and low-dose rate. Methods and MaterialsThis retrospective analysis includes low- and intermediate-risk patients with prostate cancer treated between 1998 and 2018 at an National Cancer Institute–designated comprehensive cancer center. Demographics and treatment characteristics were prospectively collected. Patients had at least 2 PSA measurements within 24 months of treatment and were free from biochemical recurrence. The incidence of, time to, and risk factors for PSA nadir (nPSA) and bounce (bPSA) were analyzed at 24 months after radiation therapy. Ideal PSA kinetics were characterized for each modality and compared. ResultsOf 1042 patients, 45% had low-risk cancer, 37% favorable intermediate risk, and 19% unfavorable intermediate risk. nPSAs were higher for ablative modalities, both as absolute nPSA and relative to initial PSA. Median time to nPSA ranged from 14.8 to 17.1 months. Over 50% treated with nonablative therapy (conventionally fractionated, hypofractionated, and low-dose rate) reached an nPSA threshold of ≤0.5 ng/mL compared with 23% of stereotactic body radiation therapy and 33% of high-dose rate cohorts. The incidence of bPSA was 13.3% and not affected by treatment modality, Gleason score, or prostate volume. PSA decay rate was faster for ablative therapies in the 6- to 24-month period. ConclusionsAnalysis of PSA within 24 months after radiation therapy revealed ablative therapies are associated with a latent PSA response and higher nPSA. Multivariable logistics modeling revealed younger age, initial PSA above the median, presence of bPSA, and ablative therapy as predictors for not achieving nPSA ≤0.5 ng/mL. PSA decay rate appears to be faster in ablative therapies after a latent period. Understanding the different PSA kinetic profiles is necessary to assess treatment response and survey for disease recurrence.

Case – Prostate-specific antigen bounce: A pitfall in prostate-specific membrane antigen positron emission tomography/computed tomography interpretation

Prostate-specific antigen (PSA) “bounce,” a transient rise in PSA post-therapy, can happen after either brachytherapy (BT) or external beam radiation therapy (EBRT); however, it is more common in the former case. In general, PSA bounce tends to occur within 2–3 years of treatment, rarely exceeds levels of 2–3 ng/ml above the nadir PSA, and tends to resolve over 6–12 months. Studies have shown that prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has a high sensitivity and specificity for the detection of prostate cancer recurrence and can potentially guide therapy. Because salvage treatment (such as local or systemic salvage) may have associated morbidity, it is important to exclude the possibility of PSA bounce before proceeding with salvage treatment. We describe a case of clinically suspected local failure with initial PSA rise and suspicious PSMA PET/CT finding post-therapy that was actually related to a PSA bounce, emphasizing the need for caution in the evaluation of men where a PSA bounce may be a confounding phenomenon.

Prognostic value of PSA bounce in prostate cancer following definitive radiation therapy: a systematic review and meta-analysis.

The prognostic significance of PSA bounce following definitive radiation therapy remains controversial. To develop a sense of current opinion in this area, we performed a systematic search of the literature based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. In January 2021, we systematically searched PubMed, the Cochrane library, and Scopus for studies that compared patients who had localized prostate cancer with or without PSA bounce after definitive radiation therapy. Our objective was to evaluate the association of PSA bounce with biochemical recurrence-free survival, metastatic-free survival, cancer-specific survival, and overall survival, using multivariate Cox regression analysis. A total of 8881 patients in 10 studies matched the selection criteria for the systematic review and meta-analysis. The number of patients with PSA bounce accounted for 2706 of all 8881 patients (30.5%). PSA bounce was associated with better biochemical recurrence-free survival after definitive radiation therapy (pooled HR: 0.62, 95% CI: 0.54-0.71). Subgroup analyses also showed that PSA bounce was independently associated with decreased risk for biochemical recurrence-free survival in prostate cancer patients treated with low dose rate brachytherapy alone (pooled HR: 0.38, 95% CI: 0.27-0.55) and external beam radiotherapy alone (pooled HR: 0.71, 95% CI: 0.57-0.87). This meta-analysis indicated that PSA bounce after definitive radiation therapy is related to improved outcome in terms of biochemical failure in prostate cancer patients.

Prostate-specific antigen dynamics after neoadjuvant androgen-deprivation therapy and carbon ion radiotherapy for prostate cancer.

This study aimed to explain the dynamics of prostate-specific antigen (PSA) levels in patients with prostate cancer who were treated with carbon ion radiotherapy (CIRT) and neoadjuvant androgen-deprivation therapy (ADT). Eighty-five patients with intermediate-risk prostate cancer who received CIRT and neoadjuvant ADT from December 2015 to December 2017 were analyzed in the present study. The total dose of CIRT was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. The PSA bounce was defined as a ≥0.4 ng/ml increase of PSA levels from the nadir, followed by any decrease. PSA failure was defined using the Phoenix criteria. The median patient age was 68 (range, 48-81) years. The median follow-up duration was 33 (range, 20-48) months. The clinical T stage was T1c, T2a, and T2b in 27, 44, and 14 patients, respectively. The Gleason score was 6 in 3 patients and 7 in 82 patients. The median pretreatment PSA level was 7.37 (range, 3.33-19.0) ng/ml. All patients received neoadjuvant ADT for a median of 6 (range, 2-117) months. PSA bounces were observed in 39 patients (45.9%), occurring a median of 12 (range, 6-30) months after CIRT. PSA failure was observed in eight patients (9.4%), occurring a median of 21 (range, 15-33) months after CIRT. The 3-year PSA failure-free survival rate was 88.5%. No clinical recurrence was observed during the follow-up period. Younger age and lower T stage were significant predictors of PSA bounce. Younger age was a significant predictor of PSA failure. In this study, we identified the significant predictors of the occurrence of PSA bounce and failure. Further follow-up is needed to reveal the clinical significance of PSA dynamics.

Characteristics of PSA Bounce after Radiotherapy for Prostate Cancer: A Meta-Analysis

The rate and characteristics of prostate-specific antigen (PSA) bounce post-radiotherapy remain unclear. To address this issue, we performed a meta-analysis. Reports of PSA bounce post-radiotherapy with a cutoff of 0.2 ng/mL were searched by using Medline and Web of Science. The primary endpoint was the occurrence rate, and the secondary endpoints were bounce characteristics such as amplitude, time to occurrence, nadir value, and time to nadir. Radiotherapy modality, age, risk classification, androgen deprivation therapy, and the follow-up period were extracted as clinical variables. Meta-analysis and univariate meta-regression were performed with random-effect modeling. Among 290 search-positive studies, 50 reports including 26,258 patients were identified. The rate of bounce was 31%; amplitude was 1.3 ng/mL; time to occurrence was 18 months; nadir value was 0.5 ng/mL; time to nadir was 33 months. Univariate meta-regression analysis showed that radiotherapy modality (29.7%), age (20.2%), and risk classification (12.2%) were the major causes of heterogeneity in the rate of bounce. This is the first meta-analysis of PSA bounce post-radiotherapy. The results are useful for post-radiotherapy surveillance of prostate cancer patients.

Prostate-specific antigen (PSA) bounce following salvage radiotherapy to the prostate bed in a patient with prostate cancer post-prostatectomy.

We present a case of prostate-specific antigen (PSA) bounce in a 76year old man who underwent salvage radiotherapy to the prostate bed following biochemical relapse 6years post-radical prostatectomy for a T2N0 Gleason grade 3 + 3 prostate adenocarcinoma; 10months following completion of salvage radiotherapy for biochemical PSA recurrence of 0.2μg/L. Following undetectable results (<0.03μg/L), his PSA rose from 0.04 to 0.3μg/L with no evidence of prostate cancer recurrence before returning to undetectable levels without medical intervention. This PSA 'bounce phenomenon' is well described following radiotherapy to an intact prostate and has been proposed to be the result of a late fibrotic effect on irradiated prostate tissue. To our knowledge, this is the first case published describing the effect in the post-prostatectomy setting. It highlights the importance of serial PSA monitoring to confirm biochemical relapse before committing the patient to androgen deprivation therapy (with its inherent risks and side effects).

Kinetics of Prostate-Specific Antigen after Carbon Ion Radiotherapy for Prostate Cancer.

This study aimed to first elucidate prostate-specific antigen (PSA) kinetics in prostate cancer patients treated with carbon ion radiotherapy (CIRT). From 2010 to 2015, 131 patients with prostate adenocarcinoma treated with CIRT (57.6 Gy relative biological effectiveness (RBE) in 16 fractions) alone were recruited. PSA was measured at 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 months post-CIRT. PSA bounce was defined as PSA increase over a cutoff followed by spontaneous decrease to or below the pre-bounce nadir. PSA failure was determined using the Phoenix criteria (nadir + 2.0 ng/mL). As a result, non-failure-associated temporary increase in PSA exhibited two distinct patterns, namely a classical bounce and a surge at one month. PSA bounce of ≥0.2 ng/mL was observed in 55.7% of the patients. Bounce amplitude was <2.0 ng/mL in 97.6% of cases. Bounce occurred significantly earlier than PSA failure. Younger age was a significant predictor of bounce occurrence. Bounce positivity was a significant predictor of favorable 5-year PSA failure-free survival. Meanwhile, a PSA surge of ≥0.2 ng/mL was observed in 67.9% of patients. Surge amplitude was significantly larger than bounce amplitude. Larger prostate volume was a significant predictor of PSA surge occurrence. PSA surge positivity did not significantly predict PSA failure. In summary, PSA bounce was distinguishable from PSA failure with regard to timing of occurrence and amplitude (earlier and lower for bounce, respectively). These data are useful for post-CIRT surveillance of prostate cancer patients.

Prostate-specific antigen bounce after 125I-brachytherapy for prostate cancer is a favorable prognosticator in patients who are biochemical recurrence-free at 4years and correlates with testosterone.

Because patients with prostate-specific antigen (PSA) bounce do not experience biochemical recurrence (BCR) until PSA bounce occurs, the period until PSA bounce ends can be considered the so-called lead-time bias. Therefore, we evaluated differences in BCR-free rate in prostate cancer patients who were BCR-free 4years after 125I-brachytherapy alone. Furthermore, we evaluated predictors for PSA bounce and the correlation between testosterone and PSA bounce. From 2004 to 2012, 256 patients with prostate adenocarcinoma underwent 125I-brachytherapy alone. PSA and testosterone levels were monitored prior to 125I-brachytherapy, at 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60months after 125I-brachytherapy and yearly after 5-year follow-up. PSA bounce was defined as ≥0.2ng/ml increase above the interval PSA nadir, followed by a decrease to nadir or below. BCR-free rate in patients with PSA bounce (100% 7-year BCR-free rate) was significantly better (P<0.044) than that in patients without PSA bounce (95.7% 7-year BCR-free rate) in patients who were BCR-free 4years after 125I-brachytherapy alone (n=223). Age was the only predictor (odds ratio: 0.93, 95% confidence interval: 0.88-0.98, P=0.004) for PSA bounce (n=177). The testosterone level at PSA bounce was significantly higher (P=0.036) than that at nadir before PSA bounce (87 cases). Patients with PSA bounce had good BCR-free rate even in patients who were BCR-free 4years after 125I-brachytherapy alone. Testosterone levels were higher at PSA bounce; increased testosterone levels may be a cause of PSA bounce.

Racial differences in the PSA bounce in predicting prostate cancer outcomes after brachytherapy: Evidence from the Department of Veterans Affairs

PurposeAfrican American men have historically had poorer prostate cancer biochemical and survival outcomes than Caucasians. However, emerging data suggest nononcologic factors drive much of this disparity. Prior evidence has suggested an association between a transient prostate specific antigen (PSA) bounce and improved biochemical control. However, racial differences in this relationship have remained relatively unexplored. Methods and MaterialsWe identified 4477 men treated for low- or intermediate-risk prostate cancer within the U.S. Department of Veterans Affairs (VA) from 2000 to 2010 with brachytherapy alone or in combination with external beam radiotherapy without androgen deprivation. Longitudinal PSA data were used to define to biochemical failure and PSA bounce. Cox proportional hazard models were used explore racial differences in the relationship between the PSA bounce and time to biochemical failure. ResultsThirty-one percent of our sample experienced a PSA bounce, with African Americans more likely to experience a bounce (42%) compared with Caucasians (29%); p < 0.001. Despite this, African Americans had a higher likelihood of biochemical failure (hazard ratio [HR] 1.4; p = 0.006). However, African American men experiencing a PSA bounce were less likely to experience a biochemical failure (HR = 0.64; p = 0.046), whereas this relationship was not statistically significant for Caucasians (HR = 0.78; p = 0.092). On multivariate analysis, African Americans receiving brachytherapy alone were most sensitive to the protective benefit of the PSA bounce (HR = 0.64). ConclusionsA PSA bounce was associated with improved biochemical control among patients receiving brachytherapy as part of their treatment for low- or intermediate-risk prostate cancer at the VA. African American men treated with brachytherapy had a particularly pronounced biochemical control benefit of a PSA bounce.

Феномен «биохимического скачка простат-специфического антигена» (bounce) после внутритканевой лучевой терапии рака предстательной железы источником высокой мощности дозы в режиме монотерапии

Феномен «биохимического скачка простат-специфического антигена» (bounce) после внутритканевой лучевой терапии рака предстательной железы источником высокой мощности дозы в режиме монотерапии

Multi-Institutional Analysis of Prostate-Specific Antigen Kinetics After Stereotactic Body Radiation Therapy

Understanding prostate-specific antigen (PSA) kinetics after radiation therapy plays a large role in the management of patients with prostate cancer (PCa). This is particularly true in establishing expectations regarding PSA nadir (nPSA) and PSA bounces, which can be disconcerting. As increasingly more patients are being treated with stereotactic body radiation therapy (SBRT) for low- and intermediate-risk PCa, it is imperative to understand the PSA response to SBRT. PSA data from 5 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2004 to 2016. Patients received 35 to 40 Gy in 5 fractions, per institutional standards. Patients who had less than 12 months of PSA data or received androgen deprivation therapy were excluded from this study. Linear and logistic multivariable analysis were performed to identify predictors of nPSA, bounce, and biochemical recurrence, and joint latent class models were developed to identify significant predictors of time to biochemical failure. A total of 1062 patients were included in this study. Median follow-up was 66 months (interquartile range [IQR], 36.4-89.9 months). Biochemical failure per the Phoenix criteria occurred in 4% of patients. Median nPSA was 0.2 ng/mL, median time to nPSA was 40 months, 84% of patients had an nPSA ≤0.5 ng/mL, and 54% of patients had an nPSA ≤0.2 ng/mL. On multivariable analysis, nPSA was a significant predictor of biochemical failure. Benign PSA bounce was noted in 26% of patients. The median magnitude of PSA bounce was 0.52 ng/mL (IQR, 0.3-1.0 ng/mL). Median time to PSA bounce was 18.1 months (IQR, 12.0-31.1 months). On multivariable analysis, age and radiation dose were significantly associated with a lower incidence of bounce. Joint latent class models modeling found that nPSA and radiation dose were significantly associated with longer time to biochemical failure. In this multi-institutional cohort of patients with long-term follow-up, we found that SBRT led to low nPSAs. In turn, lower nPSAs are associated with reduced incidence of, and longer time to, biochemical failure. Benign PSA bounces occurred in a quarter of patients, as late as several years after treatment. Further studies are needed to directly compare the PSA response of patients who receive SBRT versus other treatment modalities.

Prostate-specific Antigen Bounce After Stereotactic Body Radiotherapy for Prostate Cancer: A Pooled Analysis of Four Prospective Trials

AimsWe conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time–dose–fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA < 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored. Materials and methodsThe study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis. ResultsIn total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26–0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04–0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09–0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08–1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28–11.07) with BFFS. ConclusionThe incidence of PSA bounce was independent of time–dose–fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.

Racial Differences in the Role of the PSA Bounce in Predicting Prostate Cancer Outcomes after Radiotherapy: Evidence from the Department of Veterans Affairs

Racial Differences in the Role of the PSA Bounce in Predicting Prostate Cancer Outcomes after Radiotherapy: Evidence from the Department of Veterans Affairs

Editorial Comment

Monitoring prostate-specific antigen (PSA) is the mainstay of evaluating definitive therapy in that a rising PSA is predictive of developing distant metastases and prostate cancer-specific mortality (PCSM). Recent studies have identified post treatment PSA based surrogates for PCSM which is important given that it takes 10-20years to die after unsuccessful definitive therapy. 1 Royce TJ Chen MH Wu J et al. Surrogate end point for all-cause mortality in men with localized unfavorable -risk prostate cancer treated with radiation therapy vs radiation therapy plus androgen deprivation therapy: a secondary analysis of a randomized clinical trial. JAMA Oncol. 2017; 3: 652-658 Crossref PubMed Scopus (34) Google Scholar , 2 Romesser PB Pei X Shi W et al. Prostate-Specific Antigen (PSA) bounce after dose-escalated external beam radiation therapy is an independent predictor of PSA recurrence, metastasis, and survival in prostate adenocarcinoma patients. Int J Radiat Oncol Biol Phys. 2018; 100: 59-67 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar In this article, investigators describe an analysis of 204 men with unfavorable prostate cancer enrolled in a randomized clinical trial comparing 70.2 Gy external beam radiotherapy with or without 6 months of androgen deprivation (ADT). With a median follow-up more than 18years, men with a PSA nadir >0.2ng/mL and a time to nadir (TTN) <12 months had a statistically significant increased PCSM rate. The authors conclude that these observations infer a high likelihood of castrate resistant prostate cancer (CRPC) and propose that men with a measurable PSA nadir and a short TTN be considered for randomized trials evaluating the impact on survival of salvage ADT with or without novel agents shown to prolonged survival in men with CRPC.