Prostate cancer radiation dose response: Results of the M. D. Anderson phase III randomized trial

Alan Pollack, Gunar K. Zagars, George Starkschall, John A. Antolak, J. Jack Lee, Eugene Huang, Andrew C. Von Eschenbach, Deborah A. Kuban, Isaac Rosen

Research output: Contribution to journalArticle

1084 Citations (Scopus)

Abstract

Purpose: A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer. Methods and Materials: A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis. Results: There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64% and 70%, respectively (p = 0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62% for the 78 Gy arm vs. 43% for those who received 70 Gy (p = 0.01). For patients with a pretreatment PSA ≤10 ng/mL, no significant dose response was found, with an average 6-year FFF rate of about 75%. Although no difference occurred in overall survival, the freedom from distant metastasis rate was higher for those with PSA levels >10 ng/mL who were treated to 78 Gy (98% vs. 88% at 6 years, p = 0.056). Rectal side effects were also significantly greater in the 78 Gy group. Grade 2 or higher toxicity rates at 6 years were 12% and 26% for the 70 Gy and 78 Gy arms, respectively (p = 0.001). Grade 2 or higher bladder complications were similar at 10%. For patients in the 78 Gy arm, Grade 2 or higher rectal toxicity correlated highly with the proportion of the rectum treated to >70 Gy. Conclusion: An increase of 8 Gy resulted in a highly significant improvement in FFF for patients at intermediate-to-high risk, although the rectal reactions were also increased. Dose escalation techniques that limit the rectal volume that receives ≥70 Gy to <25% should be used.

Original languageEnglish
Pages (from-to)1097-1105
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume53
Issue number5
DOIs
StatePublished - Aug 1 2002
Externally publishedYes

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antigens
Prostate-Specific Antigen
Prostatic Neoplasms
cancer
Radiation
dosage
radiation
pretreatment
grade
Random Allocation
toxicity
radiation therapy
Radiotherapy
rank tests
rectum
Neoplasm Grading
bladder
Kaplan-Meier Estimate
metastasis
Survival Analysis

Keywords

  • Dose
  • Prostate-specific antigen
  • Radiotherapy
  • Rectal toxicity

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Prostate cancer radiation dose response : Results of the M. D. Anderson phase III randomized trial. / Pollack, Alan; Zagars, Gunar K.; Starkschall, George; Antolak, John A.; Lee, J. Jack; Huang, Eugene; Von Eschenbach, Andrew C.; Kuban, Deborah A.; Rosen, Isaac.

In: International Journal of Radiation Oncology Biology Physics, Vol. 53, No. 5, 01.08.2002, p. 1097-1105.

Research output: Contribution to journalArticle

Pollack, A, Zagars, GK, Starkschall, G, Antolak, JA, Lee, JJ, Huang, E, Von Eschenbach, AC, Kuban, DA & Rosen, I 2002, 'Prostate cancer radiation dose response: Results of the M. D. Anderson phase III randomized trial', International Journal of Radiation Oncology Biology Physics, vol. 53, no. 5, pp. 1097-1105. https://doi.org/10.1016/S0360-3016(02)02829-8
Pollack, Alan ; Zagars, Gunar K. ; Starkschall, George ; Antolak, John A. ; Lee, J. Jack ; Huang, Eugene ; Von Eschenbach, Andrew C. ; Kuban, Deborah A. ; Rosen, Isaac. / Prostate cancer radiation dose response : Results of the M. D. Anderson phase III randomized trial. In: International Journal of Radiation Oncology Biology Physics. 2002 ; Vol. 53, No. 5. pp. 1097-1105.
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abstract = "Purpose: A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer. Methods and Materials: A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis. Results: There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64{\%} and 70{\%}, respectively (p = 0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62{\%} for the 78 Gy arm vs. 43{\%} for those who received 70 Gy (p = 0.01). For patients with a pretreatment PSA ≤10 ng/mL, no significant dose response was found, with an average 6-year FFF rate of about 75{\%}. Although no difference occurred in overall survival, the freedom from distant metastasis rate was higher for those with PSA levels >10 ng/mL who were treated to 78 Gy (98{\%} vs. 88{\%} at 6 years, p = 0.056). Rectal side effects were also significantly greater in the 78 Gy group. Grade 2 or higher toxicity rates at 6 years were 12{\%} and 26{\%} for the 70 Gy and 78 Gy arms, respectively (p = 0.001). Grade 2 or higher bladder complications were similar at 10{\%}. For patients in the 78 Gy arm, Grade 2 or higher rectal toxicity correlated highly with the proportion of the rectum treated to >70 Gy. Conclusion: An increase of 8 Gy resulted in a highly significant improvement in FFF for patients at intermediate-to-high risk, although the rectal reactions were also increased. Dose escalation techniques that limit the rectal volume that receives ≥70 Gy to <25{\%} should be used.",
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AU - Pollack, Alan

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AU - Starkschall, George

AU - Antolak, John A.

AU - Lee, J. Jack

AU - Huang, Eugene

AU - Von Eschenbach, Andrew C.

AU - Kuban, Deborah A.

AU - Rosen, Isaac

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N2 - Purpose: A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer. Methods and Materials: A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis. Results: There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64% and 70%, respectively (p = 0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62% for the 78 Gy arm vs. 43% for those who received 70 Gy (p = 0.01). For patients with a pretreatment PSA ≤10 ng/mL, no significant dose response was found, with an average 6-year FFF rate of about 75%. Although no difference occurred in overall survival, the freedom from distant metastasis rate was higher for those with PSA levels >10 ng/mL who were treated to 78 Gy (98% vs. 88% at 6 years, p = 0.056). Rectal side effects were also significantly greater in the 78 Gy group. Grade 2 or higher toxicity rates at 6 years were 12% and 26% for the 70 Gy and 78 Gy arms, respectively (p = 0.001). Grade 2 or higher bladder complications were similar at 10%. For patients in the 78 Gy arm, Grade 2 or higher rectal toxicity correlated highly with the proportion of the rectum treated to >70 Gy. Conclusion: An increase of 8 Gy resulted in a highly significant improvement in FFF for patients at intermediate-to-high risk, although the rectal reactions were also increased. Dose escalation techniques that limit the rectal volume that receives ≥70 Gy to <25% should be used.

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KW - Prostate-specific antigen

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