Preliminary Results of a Randomized Radiotherapy Dose-Escalation Study Comparing 70 Gy With 78 Gy for Prostate Cancer

2000 ◽  
Vol 18 (23) ◽  
pp. 3904-3911 ◽  
Author(s):  
Alan Pollack ◽  
Gunar K. Zagars ◽  
Lewis G. Smith ◽  
J. Jack Lee ◽  
Andrew C. von Eschenbach ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dose Escalation ◽  
Proportional Hazards ◽  
External Beam Radiotherapy ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Dose Escalation Study ◽  
Radiotherapy Dose

PURPOSE: To determine the effect of radiotherapy dose on prostate cancer patient outcome and biopsy positivity in a phase III trial. PATIENTS AND METHODS: A total of 305 stage T1 through T3 patients were randomized to receive 70 Gy or 78 Gy of external-beam radiotherapy between 1993 and 1998. Of these, 301 were assessable; stratification was based on pretreatment prostate-specific antigen level (PSA). Dose was prescribed to the isocenter at 2 Gy per fraction. All patients underwent planning pelvic computed tomography scan to confirm prostate position. Treatment failure was defined as an increasing PSA on three consecutive follow-up visits or the initiation of salvage treatment. Median follow-up was 40 months. RESULTS: One hundred fifty patients were randomized to the 70-Gy arm and 151 to the 78-Gy arm. The difference in freedom from biochemical and/or disease failure (FFF) rates of 69% and 79% for the 70-Gy and 78-Gy groups, respectively, at 5 years was marginally significant (log-rank P = .058). Multiple-covariate Cox proportional hazards regression showed that the study randomization was an independent correlate of FFF, along with pretreatment PSA, Gleason score, and stage. The patients who benefited most from the 8-Gy dose escalation were those with a pretreatment PSA of more than 10 ng/mL; 5-year FFF rates were 48% and 75% (P = .011) for the 70-Gy and 78-Gy arms, respectively. There was no difference between the arms (∼80% 5-year FFF) when the pretreatment PSA was ≤ 10 ng/mL. CONCLUSION: A modest dose increase of 8 Gy using conformal radiotherapy resulted in a substantial improvement in prostate cancer FFF rates for patients with a pretreatment PSA of more than 10 ng/mL. These findings document that local persistence of prostate cancer in intermediate- to high-risk patients is a major problem when doses of 70 Gy or less are used.

scholarly journals Prospective Study of Determinants and Outcomes of Deferred Treatment or Watchful Waiting Among Men With Prostate Cancer in a Nationwide Cohort

2009 ◽  
Vol 27 (30) ◽  
pp. 4980-4985 ◽  
Author(s):  
William V. Shappley ◽  
Stacey A. Kenfield ◽  
Julie L. Kasperzyk ◽  
Weiliang Qiu ◽  
Meir J. Stampfer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prospective Study ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Deferred Treatment ◽  
Cox Proportional Hazards Models ◽  
A Prospective Study

Purpose To examine consequences of deferred treatment (DT) as initial management of prostate cancer (PCa) in a contemporary, prospective cohort of American men diagnosed with PCa. Participants and Methods We evaluated deferred treatment for PCa in the Health Professionals Follow-up Study, a prospective study of 51,529 men. Cox proportional hazards models were used to calculate hazard ratios (HRs) for time to eventual treatment among men who deferred treatment for more than 1 year after diagnosis. HRs for time to metastasis or death as a result of PCa were compared between patients who deferred treatment and those who underwent immediate treatment within 1 year of diagnosis. Results From among 3,331 cohort participants diagnosed with PCa from 1986 to 2007, 342 (10.3%) initially deferred treatment. Of these, 174 (51%) remained untreated throughout follow-up (mean 7.7 years); the remainder were treated an average of 3.9 years after diagnosis. Factors associated with progression to treatment among DT patients included younger age, higher clinical stage, higher Gleason score, and higher prostate-specific antigen at diagnosis. We observed similar rates for development of metastases (n = 20 and n = 199; 7.2 v 8.1 per 1,000 person-years; P = .68) and death as a result of PCa (n = 8 and n = 80; 2.4 v 2.6 per 1,000 person-years; P = .99) for DT and immediate treatment, respectively. Conclusion In this nationwide cohort, more than half the men who opted for DT remained without treatment for 7.7 years after diagnosis. Older men and men with lesser cancer severity at diagnosis were more likely to remain untreated. PCa mortality did not differ between DT and active treatment patients.

Intraprostatic calcification and biochemical recurrence in men treated with Cs-131 prostate brachytherapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 237-237
Author(s):  
Michael D Schad ◽  
Joshua L Rodríguez-López ◽  
Ankur Patel ◽  
Christopher J Houser ◽  
Zachary D Horne ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Biochemical Recurrence ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
External Beam Radiotherapy ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Prostate Brachytherapy

237 Background: Vigneault et al. reported that baseline intraprostatic calcification (IC) was associated with a higher risk of biochemical recurrence (BCR) in men treated with I-125 prostate brachytherapy (PB). Cs-131 has different physical properties than I-125. We assessed whether baseline IC was associated with BCR in men treated with Cs-131 PB. Methods: We retrospectively reviewed the records of all low-risk (LR), favorable intermediate-risk (FIR), and unfavorable IR (UIR) prostate cancer patients treated with Cs-131 PB +/- external beam radiotherapy (EBRT) from 2/2011 to 7/2018 at our institution. Patients who received hormone therapy or those with < 24 months follow-up were excluded. Baseline IC status (defined as 1 or more ICs ≥ 5 mm) and characteristics were determined on post-PB CT scans. Baseline patient characteristics were compared via χ2, Mann–Whitney U, or Student’s t-test. Predictors of BCR (Phoenix definition) were analyzed via Cox proportional hazards model and Kaplan–Meier survival curves were generated. Results: Two hundred and sixteen LR, FIR, and UIR prostate cancer patients treated with Cs-131 PB +/- EBRT were included. Median follow up was 56.9 months (range 24.1–111.4 months). 76 patients (35.2%) had baseline IC and 140 patients (64.8%) did not. Baseline disease characteristics did not differ significantly between patients with vs. without ICs. In patients with baseline IC, the median number of ICs was 1 (range 1–3), median length of largest IC was 9.1 mm (range 5.0–33.1), and median peak density of largest IC was 884 Hounsfield units (range 283–1744). ICs were most commonly present in the midgland (88.2%) and central (97.4%) regions. On univariate Cox analysis of all baseline disease, treatment, and IC characteristics, only initial PSA (p = 0.016) and NCCN risk group (p = 0.047) were significant predictors of BCR, whereas baseline IC was not (p = 0.11). The 5-year BCR-free survival in patients with vs. without baseline IC was 97.7% vs. 93.8% (p = 0.40), respectively. Conclusions: In a cohort of LR and IR prostate cancer patients treated with Cs-131 PB, the rate of BCR in men with baseline IC was low and baseline IC was not associated with a higher risk of BCR.

Overall survival (OS) and metastasis-free survival (MFS) by depth of prostate-specific antigen (PSA) decline in the phase III PROSPER trial of men with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide (ENZA).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 94-94
Author(s):  
Maha H. A. Hussain ◽  
Cora N. Sternberg ◽  
Eleni Efstathiou ◽  
Karim Fizazi ◽  
Qi Shen ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Reference Group ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Analysis Model ◽  
Increased Risk ◽  
Psa Nadir ◽  
Post Hoc

94 Background: The PROSPER trial demonstrated prolonged MFS and OS for men with nmCRPC and rapidly rising PSA treated with ENZA vs placebo, both in combination with androgen deprivation therapy (ADT). The final survival analysis of PROSPER (Sternberg et al. NEJM 2020) recently reported a median OS of 67.0 months (95% CI, 64.0 to not reached) with ENZA and 56.3 months (95% CI, 54.4 to 63.0) with placebo (hazard ratio [HR] for death, 0.73; 95% CI, 0.61 to 0.89; P = .001). Post hoc analyses of PROSPER evaluating PSA dynamics have demonstrated longer MFS with greater PSA decline (Hussain et al. ESMO Sept 19-21, 2020. Poster 685P) and increased risk of metastases in patients with even modest PSA progression vs those without (Saad et al. Eur Urol 2020). Here we further explored the relationship between PSA dynamics and outcomes in PROSPER using uniquely defined PSA subgroups of decline. Methods: Eligible men in PROSPER had nmCRPC, a PSA level ≥ 2 ng/mL at baseline, and a PSA doubling time ≤ 10 months. Men continued ADT, were randomized 2:1 to ENZA 160 mg once daily vs placebo, and had PSA evaluation at week 17 and every 16 weeks thereafter. This post hoc analysis evaluated OS and MFS for 4 mutually exclusive subgroups defined by PSA nadir using men with PSA reduction < 50% as the reference group. The HR is based on an unstratified Cox proportional hazards analysis model. Results: 1401 men were enrolled in PROSPER; 933 were treated with ENZA and PSA data were available for 905. Measured at nadir, 38% of these men achieved PSA reduction ≥ 90% (actual nadir < 0.2 ng/mL), and another 27% achieved PSA reduction ≥ 90% (actual nadir ≥ 0.2 ng/mL). Among men in the placebo arm of PROSPER only 3/457 reported PSA reduction ≥ 90%. Median OS and MFS increased with increasing depth of PSA decline (Table). Conclusions: In men with nmCRPC and rapidly rising PSA treated with ADT plus ENZA, there was a close relationship between the degree of PSA decline and survival outcomes. Defining PSA by both percent decline and actual decline below 0.2 ng/mL revealed a previously under-appreciated relationship between these PSA metrics and highlights the importance of PSA nadir as an intermediate biomarker in nmCRPC. Clinical trial information: NCT02003924. [Table: see text]

Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial

2018 ◽  
Vol 36 (5) ◽  
pp. 446-453 ◽  
Author(s):  
Piet Ost ◽  
Dries Reynders ◽  
Karel Decaestecker ◽  
Valérie Fonteyne ◽  
Nicolaas Lumen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Specific Antigen ◽  
Phase Iii ◽  
Curative Intent ◽  
Free Survival ◽  
Local Progression ◽  
Randomized Phase Ii

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography–computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)–free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

Association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 118-118
Author(s):  
G. Sonpavde ◽  
G. R. Pond ◽  
W. R. Berry ◽  
R. De Wit ◽  
M. A. Eisenberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Objective Assessment ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier

118 Background: In men with metastatic castration resistant prostate cancer (CRPC),the association of measurable tumor responses with overall survival (OS) is unknown. We retrospectively evaluated the TAX327 phase III trial to study this relationship. Methods: Eligible patients for this analysis included those with WHO-defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated using the Kaplan-Meier method and the prognostic relationship of WHO-defined radiologic response with OS was performed using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and 2, 3, 4 and 6 months after baseline. Results: Four hundred and twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty-seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD,24%) and 160 (38.8%) did not have a post-baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months), or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. We found a significant association between ≥30% PSA declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD and 34.4% with PD. Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain-response and ≥30% PSA-decline (p=0.009). Conclusions: In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS, and appears to complement PSA assessment. [Table: see text]

The relative contributions of the Genomic Prostate Score and comorbidity profile in predicting outcomes in surgically treated men with clinically low and intermediate-risk prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16607-e16607
Author(s):  
Jennifer Cullen ◽  
Dudith Pierre-Victor ◽  
H. Jeffrey Lawrence ◽  
Huai-Ching Kuo ◽  
Isabell Sesterhenn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Intermediate Risk ◽  
Free Survival ◽  
Risk Prostate Cancer ◽  
Risk Stratum ◽  
Diagnostic Biopsy ◽  
Using Data

e16607 Background: The 17-gene Oncotype Dx Genomic Prostate Score® (GPS™) assay has been validated as a predictor of aggressive prostate cancer (PCa) in men treated with radical prostatectomy (RP) for clinically low and intermediate risk PCa. This study examined the performance of the GPS assay as a predictor of adverse pathology (AP) and biochemical recurrence (BCR)-free survival (BRFS), after adjusting for the presence of major comorbidities commonly seen in older men. Methods: Additional analyses were performed using data from a prior clinical validation study of the GPS assay. GPS values (scaled 0-100), determined from diagnostic biopsy tissue, were categorized into 3 levels: lowest quartile (Q1), middle quartiles (combined Q2-Q3) versus the highest quartile (Q4). Major comorbidities included heart disease, stroke, COPD, and other cancers. The associations between GPS result and the presence of ≥1 major comorbidity and outcomes were examined. AP was defined as high-grade (Gleason Score ≥ 4+3) and/or pT3 tumor. BCR was defined as 2 successive PSA levels > 0.2 ng/mL. Logistic regression analysis was used to examine AP; Cox proportional hazards analysis was used to model BRFS. Results: Among 389 eligible men, median age at diagnosis and follow-up time was 62 and 5.6 years, respectively. The prevalence of ≥1 major comorbidity differed significantly across GPS category, rising from 10.2% to 19.7% to 25.5% for GPS Quartiles 1, 2-3, and 4, respectively (p = 0.0024). However, presence of ≥1 major comorbidity was not a significant predictor of AP or BCR in multivariable models with GPS, age, race, and NCCN risk stratum. Men whose GPS result was in the highest quartile had 4-fold higher odds of AP (OR: 4.1; 95% CI = 2.1-7.99, p < 0.0001) at RP and a 3.5 times higher risk of BCR (HR = 3.49; 95% CI = 1.59-7.64, p = 0.002) compared to men in the lowest GPS quartile (Table 1). Conclusions: A high GPS result remains the strongest predictor of BCR and AP in this cohort of low and intermediate risk PCa men, after adjusting for the presence of major comorbidities. Further work will explore the relationships between specific comorbidities and metabolic syndrome, with GPS testing and PCa outcomes.

Preoperative Combined Nested Reverse Transcriptase Polymerase Chain Reaction for Prostate-Specific Antigen and Prostate-Specific Membrane Antigen Does Not Correlate With Pathologic Stage or Biochemical Failure in Patients With Localized Prostate Cancer Undergoing Radical Prostatectomy

2002 ◽  
Vol 20 (15) ◽  
pp. 3213-3218 ◽  
Author(s):  
John Thomas ◽  
Manjula Gupta ◽  
Ying Grasso ◽  
Chandana A. Reddy ◽  
Warren D. Heston ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Proportional Hazards ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Biochemical Failure ◽  
Localized Prostate Cancer ◽  
Rt Pcr ◽  
Pathologic Stage ◽  
Kaplan Meier

PURPOSE: We report a prospective study examining the ability of preoperative nested reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) to predict pathologic stage and biochemical recurrence in patients with clinically localized prostate cancer treated with radical prostatectomy.PATIENTS AND METHODS: One hundred forty-one patients were entered onto the study. Preoperative evaluation included clinical T stage, serum PSA, biopsy Gleason score, and serum RT-PCR for PSA/PSM. Univariate and multivariate logistic regression models, Kaplan-Meier estimates, and Cox proportional hazards modeling were used to identify predictors of pathologic stage and biochemical failure.RESULTS: Seventy-three patients (51.8%) were RT-PCR positive for PSA, PSM, or both. In the multivariate logistic regression model, only initial PSA was an independent predictor of pathologic stage as defined by organ-confined disease (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.13; P = .026) or organ-/specimen-confined disease (OR, 1.09; 95% CI, 1.02 to 1.16; P = .009). Overall Kaplan-Meier biochemical relapse-free survival (bRFS) was 85% at 59 months. Multivariate analysis of predictors for bRFS with the Cox proportional hazards model indicated that only initial PSA (OR, 1.05; 95% CI, 1.02 to 1.09; P = .004) and biopsy Gleason score (OR, 3.57; 95% CI, 1.37 to 9.58; P = .009) were independent predictors of biochemical failure. RT-PCR status did not predict pathologic stage or biochemical failure. Repeat analysis excluding 27 patients who received preoperative androgen-deprivation therapy did not change the results.CONCLUSION: Combined nested RT-PCR for PSA and PSM is not an independent predictor of pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy. This assay has no clinical utility in this patient population.

Apatinib in combination with hypofractionation radiotherapy in bone metastatic prostate cancer: Results from a pilot, multicenter study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16523-e16523
Author(s):  
Ming Zeng ◽  
Feng Zhao ◽  
Wei Tian
Keyword(s):  
Prostate Cancer ◽  
Dose Escalation ◽  
Pain Control ◽  
Metastatic Prostate Cancer ◽  
Specific Antigen ◽  
Growth Factor Receptor ◽  
Radiographic Evaluation ◽  
Large Sample Size ◽  
Dose Escalation Study ◽  
Hand Foot Syndrome

e16523 Background: To study safety and efficacy of apatinib, a vascular endothelial growth factor receptor-2 (VEGF2) inhibitor, in combination with radiotherapy in patients with bone metastatic prostate cancer (BMPC), based on potential synergistic antitumor activities of apatinib and Radiation Therapy (RT). Methods: In a dose escalation study, 18 patients (6/cohort) received apatinib at 250 mg every other day, 250 mg or 500 mg daily. The 250 mg daily cohort was expanded to 19 patients in combination with RT (6 Gy/fraction, 5 fraction in total), comparing with the RT alone cohort with 10 patients. Evaluations included adverse events (AEs), prostate specific antigen (PSA) levels, radiographic evaluation and pain relief. Results: In the dose escalation patients, common apatinib-related AEs (arAEs) were fatigue (11, 61%), anorexia 10, 55%), hand foot syndrome (9, 50%), proteinuria (8, 44%), and HTN (8, 44%). Grade 3 arAEs included HTN, proteinuria, and liver dysfunction. No treatment-related death occurred. In the apatinib plus RT cohort, AEs were increased comparing to either apatinib alone or RT alone; The combination cohort showed improvement in pain control. Conclusions: In BMPC patients, apatinib at less than 500 mg daily dose as mono-therapy had tolerable toxicity, consistent with previous reports in patients with other tumors. Apatinib at dose of 250mg daily combining with RT improved pain control while the overall AEs were manageable. Further studies are needed in large sample size trials. Clinical trial information: NCT02998242.

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