Prospective Long-Term Patient-Reported Quality of Life After Proton Therapy for Prostate Cancer

Reporter: Abigail T. Berman, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 4, 2013

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Presenting Author: Andrew K. Lee, MD
Presenting Author Affiliation: M.D. Anderson Cancer Center, Houston, TX

Background

  • Prostate cancer is the most common malignancy in males. Its incidence has increased with the use of PSA screening. Treatment options for prostate cancer include active surveillance, radiation, administered as external beam radiation or brachytherapy, or surgery. For external beam radiation, this can be administered using photon therapy (3D conformal or intensity modulated radiotherapy), or by proton therapy.
  • Because the cause-specific survival of low-risk prostate cancer is excellent in the 90-95% range, treatment choice is largely driven by side effects after treatment. After prostate cancer treatment, the worrisome side effects include urinary, bowel, and erectile problems.
  • Patient-reported quality of life studies help accurately portray how patients feel their urinary, bowel, and erectile functions have been affected by prostate cancer treatment.
  • Proton beam therapy, due to its characteristic Bragg peak, may decrease the risk of adverse events after prostate cancer treatment.
  • The purpose of this study was to prospectively evaluate patient-reported quality of life (QOL) after proton therapy for prostate cancer (PCa).

Materials/Methods

  • PCa patients treated with proton therapy (PT) were enrolled on a prospective QOL protocol and asked to complete the Expanded Prostate Cancer Index Composite (EPIC) before PT and at 3-6 months intervals following PT.
  • Men received 75.6 Gray Equivalents (GyE) @ 1.8 GyE/fraction (n=95) or 76-78 GyE @ 2 GyE/fraction (n=147).
  • Men with baseline- and 4 year post-PT surveys were included in the analysis (n=242).
  • Statistically significant changes in mean scores from baseline were determined using a t-test, and clinically significant changes were based on changes >0.5 * standard deviation of baseline.
  • The cumulative incidence of acute and late toxicities as per modified-RTOG scale was determined.

Results

  • All men were followed for at least 4 years. Median age at diagnosis was 65.5 years (range 46-82), median pre-treatment PSA was 4.5 ng/ml (0.1-18.6), 44.6% received hormone therapy (median duration 6 months), Gleason sum 6 was seen in 40.9% and Gleason sum 7 in 59.1%.
  • Most men (61.2%) were intermediate risk and 38.8% were low risk.
  • As shown in the table, statistically significant changes from baseline at 4 years post-PT were seen in multiple sexual, urinary, bowel and hormonal/vitality domains.
  • However, clinically significant changes were not seen in any domains except for bowel scores within 3.5 years. At 4 years, no clinically significant changes were reported in any domain.
  • At 4-years, 96.3% of men reported using 0-1 urinary pad (93.4% used 0). At least "moderate" problems with urinary function, bowel habits, bloody stools and sexual function were reported in only 3.7%, 3.8%, 0.8%, and 37.6% of men, respectively.
  • The cumulative incidence of acute grade 2 urinary side effects (mostly ? blockers) was 51.2% and acute grade 2 rectal was 8.7%. No acute grade 3 or higher toxicities.
  • The cumulative incidence of late grade 2 urinary and rectal side effects were 17.4% and 12.4%.
  • One patient had a late grade 3 rectal toxicity.
  • The prevalence of late grade 2 GU/GI side effects at last contact was <2%.
  • The cumulative incidence of PSA failure using the nadir+2 definition was 6.5% for all patients, which represented several PSA bounces and one clinical failure.
  • At 4-years, 93.4% of men were "satisfied or extremely satisfied" with their treatment.

Author's Conclusions

  • In this long-term prospective study, proton therapy resulted in statistically significant but not clinically significant changes in patient-QOL at 4 years.
  • Overall, the toxicity and impact on quality of life were low.
  • Patient satisfaction rates were high.

Clinical Implications

  • Proton beam therapy can theoretically reduce acute and long-term side effects of treatment through normal tissue sparing. While this form of treatment is theoretically advantageous, it is expensive, and there has been no randomized evidence demonstrating a clinical benefit to proton therapy.
    • There is a currently ongoing randomized study at the University of Pennsylvania and Massachusetts General Hospital randomizing patients to IMRT or proton beam therapy with the primary endpoint of bowel toxicity.
  • This is a single-arm, prospective quality of life study that shows that the acute grade 2 urinary side effects occurs in approximately 50% of patients, indicating that medical management was required in approximately 50% of patients. The incidence of late grade 2 GI or GU toxicity was <2%, which is lower compared with historical controls of IMRT.
  • The largest previous study published comparing modalities is that of Sanda et al. (NEJM 2008) which showed differing quality-of-life between patients receiving brachytherapy, external-beam radiotherapy, and surgery. As an example point of comparison, they found an 11% rate of moderate or worse distress from overall urinary symptoms at 1 year, which is comparable to the findings of this study
  • Strengths of this study include that it was prospective collection, using the EPIC quality of life questionnaire, which is well validated. The follow-up in this study was excellent, with all men being followed for at least 4 years. The authors described the mechanism by which they followed the patients, which was very tedious, including permitting patients to email them about any concerning side effects.
  • The main limitation of this study is that it does not include a comparison to other treatment modalities, including IMRT. Because of the high cost of proton beam therapy, the main concern is the relative comparison in quality of life in proton versus IMRT treatment techniques.
    • There have been two publications, which have raised concern that the GI toxicity may be higher with proton beam therapy (Sheets et al. JAMA 2012).
    • Hopefully, the randomized clinical trial will bring definitive answers to this question.

MEAN EPIC SCORES 0-100 (std deviation, * denotes clinically significant change)

EPIC Domain

Baseline

1-Year

2-Year

3-Year

4-Year

Change from
baseline to 4-Year

Statistically significant change
from baseline (p-value)

CLINICALLY significiant change
from baseline (p-value)

Urinary Summary

90 (10.1)

88.9

89.8

89.4

89.7

0.3

0.935

0.99

Urinary Function

96
(8.8)

93.5

93.8

93.4

93.5

2.5

0.002

0.99

Urinary Bother

85.4 (13.2)

85.4

87

86.5

86.8

1.6

0.089

0.99

Bowel Summary

94.8 (6.1)

87.5*

89*

90.7*

91.4

3.3

<0.001

0.35

Bowel Function

93.8 (7.1)

88.2*

89.3*

90.9*

91.3

2.4

<0.001

0.95

Bowel Bother

95.7 (6.7)

87*

88.7*

90.4*

91.4

4.4

<0.001

0.99

Sexual Summary

54.5 (27.4)

51.3

49.2

48.8

46.8

7.5

<0.001

0.99

Sexual Function

50.9 (27.5)

48.3

45.9

45.3

42.7

8.0

<0.001

0.99

Sexual Bother

62.5 (33.2)

59.4

57.5

57.8

57

5.4

<0.001

0.99


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