Long-term outcomes of dose-escalated intensity modulated radiation therapy alone without androgen deprivation therapy for patients with intermediate and high-risk prostate cancer.
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PROVIDER: S-EPMC5514229 | BioStudies | 2016-01-01
REPOSITORIES: biostudies
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Project description:To gain beneficial effects in the management of high-risk prostate cancer, an integrated approach that combines local therapy and androgen deprivation therapy (ADT) was used. We compared biochemical responses between primary cryosurgical ablation of the prostate (CSAP) combined with prolonged ADT and radiation combined with ADT, which is the established modality in high-risk disease. A total of 33 high-risk patients received CSAP combined with ADT for 3 months before and up to 24 months after treatment. This patient group was matched with another 33 patients who had undergone three-dimensional conformal radiation therapy (3D-CRT) with the same protocol for ADT. Biochemical recurrence (BCR) was assessed by the American Society for Therapeutic Radiation Oncology (ASTRO) definition, the Phoenix definition and a prostate-specific antigen (PSA) cutoff of 0.5 ng mL(-1). Median follow-up was 61.0 ± 11.9 months for the CSAP + ADT group and 86.0 ± 15.8 months for the 3D-CRT + ADT group. In the CSAP group, major complications including rectourethral fistula and incontinence were not noted. In the CSAP + ADT group, 57.0% had BCR using the ASTRO definition, 21.2% using the Phoenix definition and 54.5% using a PSA cutoff of 0.5 ng mL(-1). In the 3D-CRT + ADT group, 54.5%, 21.2% and 54.5% had BCR using the ASTRO, Phoenix and PSA definition, respectively. In the CSAP + ADT group, the BCR-free survival (BRFS) was 54 ± 10 months using the ASTRO definition, 65 ± 5 months using the Phoenix definition and 51 ± 4 months using a PSA cutoff of 0.5 ng mL(-1). In the 3D-CRT + ADT group, the BRFS was 68 ± 12, 93 ± 19 and 70 ± 18 months using the ASTRO, Phoenix and PSA definition, respectively. By the log-rank test, the BRFS values for each group were not statistically different. This intermediate-term result indicated that primary CSAP combined with prolonged ADT offers a parallel biochemical response compared with radiotherapy in high-risk prostate cancer.
2010-01-01 | S-EPMC3739070 | BioStudies
Project description:The aim of this study is to investigate the effect of tumor characteristics and parameters of treatment response in predicting biochemical disease-free survival (BFS) for patients with intermediate or high risk prostate cancer treated by combined definitive external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT).Between June 1995 and January 2015, 375 patients with localized prostate cancer and a National Comprehensive Cancer Network (NCCN) intermediate or high risk categories were treated by definitive EBRT and ADT. Median duration of androgen blockade was 10 months (range: 3-36 months); Median radiation dose was 72 Gy (Range: 70-78 Gy). Median follow-up time was 5.8 years (range: 0.8-16.39 years). The main study endpoint was biochemical disease free survival (BFS).Forty seven patients (12.5%) developed biochemical recurrence (BCR) during the observation period. Monovariate analysis identified baseline PSA (bPSA) (p = 0.024), T-stage (p = 0.001), Gleason's score (GS) (p = 0.042), radiation dose (p = 0.045), PSA pre-radiation therapy (p = 0.048), and nadir PSA (nPSA), (p < 0.001) as significant variables affecting BCR. The receiver operating characteristic (ROC) curve identified a nPSA of 0.06 ng/ml as optimal cut-off value significantly predicting the patients' risk of BCR (p < 0.001). Multivariate cox regression analysis revealed T-stage, GS, and nPSA as independent variable affecting BFS, while bPSA, age, and radiation dose were not.Nadir PSA at 0.06 is a strong independent predictor of BFS in patients with intermediate or high risk prostate cancer treated by definitive EBRT and ADT.
2017-01-01 | S-EPMC5590195 | BioStudies
Project description:BACKGROUND:Androgen deprivation therapy (ADT) combined with radiation therapy benefits intermediate- and high-risk prostate cancer (PC) patients. The optimal ADT duration in combination with high-dose proton beam therapy (PBT) remains unknown. METHODS:Intermediate- and high-risk PC patients treated with PBT combined with ADT for various durations were analyzed retrospectively. To assess the relationship between ADT and biochemical relapse-free (bRF) rate, Cox proportional hazards models including T stage, prostate specific antigen (PSA) level, Gleason score (GS), and total radiation dose were used. RESULTS:In the intermediate-risk PC patients (n = 520), ADT use improved bRF (HR 0.49, 95% CI 0.26-0.93; p = 0.029), especially in those with multiple intermediate-risk factors (T2b-2c, PSA 10-20 ng/mL, and GS 7). In the high-risk PC patients (n = 555), a longer ADT duration (>6 months) conferred a benefit for bRF (HR 0.54, 95% CI 0.32-0.90; p = 0.018), which was most apparent in patients with multiple high-risk factors (T3a-4, PSA > 20 ng/mL, and GS ? 8) treated with ADT for ?21 months. CONCLUSIONS:Short-term (?6 months) ADT is beneficial for intermediate-risk PC patients, but likely unnecessary for those with a single risk factor, whereas ADT for >6 months is necessary for high-risk PC patients and ADT for ?21 months might be optimal for those with multiple risk factors in combination of high-dose PBT.
| S-EPMC7352923 | BioStudies
Project description:<h4>Purpose/objective</h4>The association of 3D Conformal External Beam Radiotherapy (3D-CEBRT) with adjuvant Androgen Deprivation Therapy (ADT) proved to treat patients with intermediate- and high-risk localized prostate cancer (IR and HR). However, older patients were underrepresented in literature. We aimed to report the oncological results and morbidity 3D-CEBRT +ADT in ?80 years patients.<h4>Material and methods</h4>From June 1998 to July 2017, 101 patients ?80 years were included in a tertiary center. The median age was 82 years. ADT was initiated 3 months prior 3D-CEBRT in all patients, with a total duration of 6 months for IR prostate cancer (group A; <i>n</i> = 41) and 15 months for HR prostate cancer (group B; <i>n</i> = 60). Endpoints included overall survival (OS), metastasis-free survival (DMFS), biochemical recurrence-free survival (BRFS) and toxicity.<h4>Results</h4>Five years-OS was 95% and 86.7% in groups A and B, respectively. Cardiovascular events occurred in 22.8% of ?80 years patients with no impact on OS. In the multivariate analysis, age <82 years, Karnofsky index and normalization of testosterone levels were significantly associated with better OS.<h4>Conclusion</h4>Age ?80 years should not be a limitation for the treatment of IR and HR prostate cancer patients with 3D-CEBRT and ADT, but cardiovascular monitoring and prevention are mandatory.
| S-EPMC7795189 | BioStudies
Project description:<h4>Importance</h4>There is a clear need for a molecular subtyping approach in prostate cancer to identify clinically distinct subgroups that benefit from specific therapies.<h4>Objectives</h4>To identify prostate cancer subtypes based on luminal and basal lineage and to determine associations with clinical outcomes and response to treatment.<h4>Design, setting, and participants</h4>The PAM50 classifier was used to subtype 1567 retrospectively collected (median follow-up, 10 years) and 2215 prospectively collected prostate cancer samples into luminal- and basal-like subtypes.<h4>Main outcomes and measures</h4>Metastasis, biochemical recurrence, overall survival, prostate cancer–specific survival, associations with biological pathways, and clinicopathologic variables were the main outcomes.<h4>Results</h4>Among the 3782 samples, the PAM50 classifier consistently segregated prostate cancer into 3 subtypes in both the retrospective and prospective cohorts: luminal A (retrospective, 538 [34.3%]; prospective, 737 [33.3%]), luminal B (retrospective, 447 [28.5%]; prospective, 723 [32.6%]), and basal (retrospective, 582 [37.1%]; prospective, 755 [34.1%]). Known luminal lineage markers, such as NKX3.1 and KRT18, were enriched in luminal-like cancers, and the basal lineage CD49f signature was enriched in basal-like cancers, demonstrating the connection between these subtypes and established prostate cancer biology. In the retrospective cohort, luminal B prostate cancers exhibited the poorest clinical prognoses on both univariable and multivariable analyses accounting for standard clinicopathologic prognostic factors (10-year biochemical recurrence-free survival [bRFS], 29%; distant metastasis-free survival [DMFS], 53%; prostate cancer-specific survival [PCSS], 78%; overall survival [OS], 69%), followed by basal prostate cancers (10-year bRFS, 39%; DMFS, 73%; PCSS, 86%; OS, 80%) and luminal A prostate cancers (10-year bRFS, 41%; DMFS, 73%; PCSS, 89%; OS, 82%). Although both luminal-like subtypes were associated with increased androgen receptor expression and signaling, only luminal B prostate cancers were significantly associated with postoperative response to androgen deprivation therapy (ADT) in a subset analysis in our retrospective cohorts (n = 315) matching patients based on clinicopathologic variables (luminal B 10-year metastasis: treated, 33% vs untreated, 55%; nonluminal B 10-year metastasis: treated, 37% vs untreated, 21%; P = .006 for interaction).<h4>Conclusions and relevance</h4>Luminal- and basal-like prostate cancers demonstrate divergent clinical behavior, and patients with luminal B tumors respond better to postoperative ADT than do patients with non–luminal B tumors. These findings contribute novel insight into prostate cancer biology, providing a potential clinical tool to personalize ADT treatment for prostate cancer by predicting which men may benefit from ADT after surgery.
| S-EPMC5824281 | BioStudies
Project description:BACKGROUND AND PURPOSE:To identify early biochemical predictors of survival in intermediate- and high-risk prostate cancer patients with a pre-treatment PSA <20?ng/mL following definitive radiation therapy (RT) and androgen deprivation therapy (ADT). MATERIALS AND METHODS:A single-institution review of 2566 intermediate and high-risk prostate cancer patients treated with definitive RT and neoadjuvant and concurrent ADT from 1990 to 2012 was performed. The first prostate-specific antigen (PSA) value within three months of ADT initiation (post-ADT PSA) and the first PSA within three months after RT completion (post-RT PSA) were recorded. 1275 had baseline PSA <20?ng/mL and either post-ADT or post-RT PSA available. Median follow-up was 7.6?years. The relationship between post-treatment PSA kinetics and biochemical relapse (BR), distant metastasis (DM), prostate cancer specific death (PCSD) and overall survival (OS) was modeled using Cox regression univariate and multivariate analysis (MVA). RESULTS:MVA demonstrated a strong association between a post-RT PSA ?0.09?ng/mL and a significantly higher risk of BR (HR: 1.93; 95% CI: 1.45-2.57; p?<?0.001), DM (HR: 2.97; 95% CI: 2.01-4.39; p?<?0.001), PCSD (HR: 2.99; 95% CI: 1.73-5.15; p?<?0.001) and OS (HR: 1.49; 95% CI: 1.18-1.86; p?<?0.001). Post-RT PSA reduction of ?95% relative to the baseline PSA was associated with a significantly lower risk of BR (MVA HR: 0.58; 95% CI: 0.41-0.83; p?=?0.003) and DM (MVA HR: 0.47; 95% CI: 0.30-0.76; p?=?0.002). CONCLUSION:A PSA value ?0.09?ng/mL early after RT completion is associated with significantly worse prognosis across all clinical outcomes, and an early PSA reduction of ?95% is associated with reduced risk of BR and DM. These findings may identify patients who require early aggressive systemic management for high-risk disease.
| S-EPMC7542885 | BioStudies
Project description:Our previous work on early PSA kinetics following prostate stereotactic body radiation therapy (SBRT) demonstrated 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).65 low- and 80 intermediate-risk PCa patients were treated definitively with SBRT to 35-37.5 Gy in 5 fractions at Georgetown University Hospital between January 2008 and October 2011. Patients who received androgen deprivation therapy were excluded from this study. Biochemical relapse was defined as a PSA rise >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 <0.2 ng/ml. Univariate logistic regression analysis was used to evaluate relevant variables on the likelihood of achieving a PSA nadir <0.2 ng/ml.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 5.6 years, 86 and 37% of patients achieved a PSA nadir ≤0.5 and <0.2 ng/ml, respectively. The median time to PSA nadir was 36 months. Two low and seven intermediate risk patients experienced a biochemical relapse. Regardless of the PSA outcome, the median PSA nadir for all patients was 0.2 ng/ml. The 5-year biochemical relapse free survival (bRFS) rate for low- and intermediate-risk patients was 98.5 and 95%, respectively. 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 <0.2 ng/ml.SBRT for low- and intermediate-risk PCa is a convenient treatment option with low PSA nadirs and a high rate of early bRFS. Fewer than 40% of patients, however, achieved an ablative PSA nadir. Thus, the role of further dose escalation is an area of active investigation.
2017-01-01 | S-EPMC5522851 | BioStudies
Project description:BACKGROUND:The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases. OBJECTIVE:To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTING, AND PARTICIPANTS:We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment. RESULTS AND LIMITATIONS:A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS). CONCLUSIONS:WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted. PATIENT SUMMARY:When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.
| S-EPMC7521828 | BioStudies
Project description:<h4>Purpose</h4>Until 2018, National Cancer Comprehensive Network guidelines recommended androgen deprivation therapy (ADT) for all men with intermediate-risk prostate cancer who had undergone radiation therapy. Intermediate risk was stratified as favorable and unfavorable in 2018, and ADT recommendation was limited to men with unfavorable intermediate-risk prostate cancer. Data suggesting this stratification and treatment deintensification were first published in December 2013. This study characterizes US national trends for demographic, clinical, and socioeconomic factors associated with ADT use in men with intermediate-risk prostate cancer who have undergone definitive radiation therapy.<h4>Methods and materials</h4>This retrospective cohort study examined 108,185 men in the National Cancer Database who were diagnosed with intermediate-risk prostate cancer from 2004 to 2016. Temporal trends in demographic, clinical, and socioeconomic factors among men with intermediate-risk prostate cancer and associations with the use of ADT were characterized.<h4>Results</h4>In total, 108,185 men diagnosed with intermediate-risk prostate cancer underwent radiation therapy from 2004 to 2016. Of these men, 41.09% received ADT. Among the 60,705 men with favorable intermediate-risk prostate cancer, 32.06% received ADT. Among the 47,480 men with unfavorable intermediate-risk prostate cancer, 52.64% received ADT. On multivariate analysis, use of ADT was associated with age and year of diagnosis; being a race other than White; having government-based insurance; having a higher prostate-specific antigen level, tumor stage, and Gleason score; receiving treatment at a nonacademic center; and receiving external beam radiation therapy alone.<h4>Conclusions</h4>The findings highlight that ADT use is variable in men undergoing definitive radiation therapy for intermediate-risk prostate cancer, with the data suggesting that several clinical and socioeconomic disparities influence its use. The findings suggest that a significant proportion of men with favorable intermediate-risk prostate cancer receive ADT and remain candidates for treatment de-escalation, whereas a significant proportion of men with unfavorable intermediate-risk prostate cancer may be undertreated when ADT is omitted.
| S-EPMC9260097 | BioStudies
Project description:Purpose: To retrospectively assess clinical outcomes and toxicity profile of prostate cancer patients treated with delayed dose-escalated image-guided salvage radiotherapy (SRT) for macroscopic local recurrence after radical prostatectomy (RP). Material and Methods: We report on a cohort of 69 consecutive patients with local recurrence after RP and no evidence of regional or distant metastasis who were referred for salvage radiotherapy between 2007 and 2016. SRT consisted of 64-66 Gy (2 Gy/fraction) to the prostatic bed followed by dose escalation to 72-74 Gy (2Gy/fraction) to the macroscopic disease. All patients received concurrent short-term androgen deprivation therapy (ADT). Biochemical recurrence-free survival (bRFS) and clinical progression-free-survival (cPFS) were depicted using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predictors of survival outcomes. Baseline, acute, and late urinary and gastrointestinal (GI) toxicity rates were reported using CTCAE v4.03. Results: Median time from RP to SRT was 66 months (IQR: 32-124). Median pre-SRT prostate-specific antigen (PSA) was 2.7 ng/ml (IQR: 0.9-6.5). Median follow-up after SRT was 38 months (IQR: 24-66). The 3- and 5-year bRFS were 58 and 44%, respectively. The 3- and 5-year cPFS were 91 and 76%, respectively. Median time from SRT to clinical disease progression was 102 months (IQR 77.5-165). At baseline, 3 patients (4%) had grade 3 urinary symptoms. Six patients (9%) developed acute and six patients (9%) developed late grade 3 urinary toxicity. Five patients (7%) had acute grade 2 GI toxicity. No acute grade 3 GI toxicity was reported. Late grade 3 GI toxicity was reported in one patient (1.5%). Conclusions: Delayed dose-escalated SRT combined with short-course ADT for macroscopic LR after RP was associated with 44% bRFS and 76% cPFS at 5 years. Albeit improved patient stratification is warranted, these data suggest that delayed SRT provides inferior tumor control compared to early intervention.
| S-EPMC6403145 | BioStudies