Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Radiation Oncology
Published in: Radiation Oncology 1/2015

Open Access 01-12-2015 | Research

The impact of increasing dose on overall survival in prostate cancer

Authors: Matthew D. Hall, Timothy E. Schultheiss, David D. Smith, Bertrand P. Tseng, Jeffrey Y. C. Wong

Published in: Radiation Oncology | Issue 1/2015

Login to get access

Abstract

Purpose

To assess the impact of increasing dose on overall survival (OS) for prostate cancer patients.

Methods

Treatment data were obtained on more than 20,000 patients in the National Oncology Data Alliance®, a proprietary database of merged tumor registries, who were treated for prostate cancer with definitive radiotherapy between 1995 and 2006. Eligible patients had complete data on total dose, T stage, use and timing of androgen deprivation therapy (ADT), and treatment start date (n = 20,028). Patients with prior malignancies were excluded.

Results

On multivariate analysis, dose, T stage, grade, marital status, age, and neoadjuvant ADT were significant predictors of OS. Hazard ratios for OS declined monotonically with increasing dose, reaching 0.63 (95 % Confidence Interval 0.53–0.76) at ≥80 Gy. On subset analysis, neoadjuvant ADT significantly improved OS in high risk patients but was not significant in lower risk patients. The dose response was maintained across all risk groups. Medical comorbidities were balanced across all dose strata and sensitivity analysis demonstrated that other prognostic factors were unlikely to explain the observed dose response.

Conclusions

This study suggests that increasing dose significantly improves OS in prostate cancer patients treated with radiotherapy.
Appendix
Available only for authorised users
Literature
1.
Zietman AL, DeSilvio ML, Slater JD, Rossi Jr CJ, Miller DW, Adams JA, et al. Comparison of conventional-dose vs. high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate. JAMA. 2005;294:1233–39.PubMedCrossRef
2.
Dearnaley DP, Sydes MR, Graham JD, Aird EG, Bottomley D, Cowan RA, et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: First results from the MRC RT01 randomised controlled trial. Lancet Oncol. 2007;8:475–87.PubMedCrossRef
3.
Al-Mamgani A, van Putten WL, Heemsbergen WD, van Leenders GJ, Slot A, Dielwart MF, et al. Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008;72(4):980–8.PubMedCrossRef
4.
Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, et al. Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70(1):67–74.PubMedCrossRef
5.
Beckendorf V, Guerif S, Le Prisé E, Cosset JM, Bougnoux A, Chauvet B, et al. 70 Gy vs. 80 Gy in localized prostate cancer: 5-year results of GETUG 06 randomized trial. Int J Radiat Oncol Biol Phys. 2011;80(4):1056–63.PubMedCrossRef
6.
Swisher-McClure S, Mitra N, Woo K, Smaldone M, Uzzo R, Bekelman JE. Increasing use of dose-escalated external beam radiation therapy for men with nonmetastatic prostate cancer. Int J Radiat Oncol Biol Phys. 2014;89(1):103–12.PubMedCentralPubMedCrossRef
7.
Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002;360(9327):103–6.PubMedCrossRef
8.
Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011;365(2):107–18.PubMedCrossRef
9.
Widmark A, Klepp O, Solberg A, Damber JE, Angelsen A, Fransson P, et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 2009;373(9660):301–8.PubMedCrossRef
10.
Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2014;378(9809):2104–11.CrossRef
11.
Nguyen KH, Horwitz EM, Hanlon AL, Uzzo RG, Pollack A. Does short-term androgen deprivation substitute for radiation dose in the treatment of high-risk prostate cancer? Int J Radiat Oncol Biol Phys. 2003;57:377–83.PubMedCrossRef
12.
Michalski JM, Moughan J, Purdy J, Bosch W, Bahary J-P, Lau HY, et al. A randomized trial of 79.2 Gy versus 70.2 Gy radiation therapy (RT) for localized prostate cancer. J Clin Oncol. 2015;33(suppl 7S; abstr 4):4.
13.
Zelefsky MJ, Fuks Z, Hunt M, Lee HJ, Lombardi D, Ling CC, et al. High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol. 2001;166(3):876–81.PubMedCrossRef
14.
Chauvet B, Alfonsi M, de Rauglaudre G, Reboul F. Prostate cancer: has local radiation treatment had an impact on survival? Cancer Radiother. 2002;6(3):141–6.PubMedCrossRef
15.
Bill-Axelson A, Holmberg L, Ruutu M, Garmo H, Stark JR, Busch C, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011;364:1708–17.PubMedCrossRef
16.
Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367:203–13.PubMedCentralPubMedCrossRef
17.
Surveillance, Epidemiology, and End Results (SEER) Program (www.​seer.​cancer.​gov) SEER*Stat Database: Incidence - SEER 18 Regs Research Data, Nov 2012 Sub (1973–2010) < Katrina/Rita Population Adjustment > − Linked To County Attributes - Total U.S., 1973–2012 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released September 2013
18.
Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The national cancer data base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2007;15(3):683–90.CrossRef
19.
Harrell Jr FE. Regression modeling strategies with applications to linear models, logistic regression, and survival analysis. New York: Springer. 2014;13–15:509–22.
20.
Lin DY, Psaty BM, Kronmal RA. Assessing the sensitivity of regression results to unmeasured confounders in observational studies. Biometrics. 1998;54(3):948–63.PubMedCrossRef
21.
Mitra N, Heitjan DF. Sensitivity of the hazard ratio to nonignorable treatment assignment in an observational study. Statist Med. 2007;26:1398–414.CrossRef
22.
Williams SG, Duchesne GM, Millar JL, Pratt GR. Both pretreatment prostate-specific antigen level and posttreatment biochemical failure are independent predictors of overall survival after radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2004;60(4):1082–7.PubMedCrossRef
23.
Armstrong JG, Gillham CM, Dunne MT, Fitzpatrick DA, Finn MA, Cannon ME, et al. A randomized trial (Irish clinical oncology research group 97–01) comparing short versus protracted neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2011;81(1):35–45.PubMedCrossRef
24.
Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh AC, Oddens J, Poortmans PM, et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med. 2009;360(24):2516–27.PubMedCrossRef
25.
Arcangeli G, Fowler J, Gomellini S, Arcangeli S, Saracino B, Petrongari MG, et al. Acute and late toxicity in a randomized trial of conventional versus hypofractionated three-dimensional conformal radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2011;79(4):1013–21.PubMedCrossRef
26.
Mendenhall NP, Hoppe BS, Nichols RC, Mendenhall WM, Morris CG, Li Z. Five-year outcomes from 3 prospective trials of image-guided proton therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2014;88(3):596–602.PubMedCrossRef
27.
Booth CM, Tannock IF. Randomised controlled trials and population-based observational research: partners in the evolution of medical evidence. Br J Cancer. 2014;110(3):551–5.PubMedCentralPubMedCrossRef
28.
Jani AB, Master VA, Rossi PJ, Liauw SL, Johnstone PA. Grade migration in prostate cancer: an analysis using the Surveillance, Epidemiology, and End Results registry. Prostate Cancer Prostatic Dis. 2007;10(4):347–51.PubMedCrossRef
29.
Tendulkar RD, Hunter GK, Reddy CA, Stephans KL, Ciezki JP, Abdel-Wahab M, et al. Causes of mortality after dose-escalated radiation therapy and androgen deprivation for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2013;87(1):94–9.PubMedCrossRef
30.
Harlan LC, Potosky A, Gilliland FD, Hoffman R, Albertsen PC, Hamilton AS, et al. Factors associated with initial therapy for clinically localized prostate cancer: prostate cancer outcomes study. J Natl Cancer Inst. 2001;93(24):1864–71.PubMedCrossRef
Metadata
Title
The impact of increasing dose on overall survival in prostate cancer
Authors
Matthew D. Hall
Timothy E. Schultheiss
David D. Smith
Bertrand P. Tseng
Jeffrey Y. C. Wong
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2015
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-015-0419-3

Other articles of this Issue 1/2015

Radiation Oncology 1/2015 Go to the issue

Study protocol

Regional hyperthermia and moderately dose-escalated salvage radiotherapy for recurrent prostate cancer. Protocol of a phase II trial

Research

Attenuation measurements show that the presence of a TachoSil surgical patch will not compromise target irradiation in intra-operative electron radiation therapy or high-dose-rate brachytherapy

Research

The effectiveness of endoscopic submucosal dissection followed by chemoradiotherapy for superficial esophageal cancer

Research

Definitive hypofractionated radiotherapy for early glottic carcinoma: experience of 55Gy in 20 fractions

Research

Evaluation of effect of body mass index and weight loss on survival of patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy

Research

Seed migration after transperineal interstitial prostate brachytherapy by using loose seeds: Japanese prostate cancer outcome study of permanent iodine-125 seed implantation (J-POPS) multi-institutional cohort study