Clinical Investigation
Dose Escalation and Quality of Life in Patients With Localized Prostate Cancer Treated With Radiotherapy: Long-Term Results of the Dutch Randomized Dose-Escalation Trial (CKTO 96-10 Trial)

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Purpose

To assess the impact of dose escalation of radiotherapy on quality of life (QoL) in prostate cancer patients.

Patients and Methods

Three hundred prostate cancer patients participating in the Dutch randomized trial (CKTO 69-10) comparing 68 Gy with 78 Gy were the subject of this analysis. These patients filled out the SF-36 QoL questionnaire before radiotherapy (baseline) and 6, 12, 24, and 36 months thereafter. Changes in QoL over time of ≥10 points were considered clinically relevant. Repeated-measures regression analyses were applied to estimate and test the QoL changes over time, the differences between the two arms, and for association with a number of covariates.

Results

At 3-year follow-up, the summary score physical health was 73.2 for the 68-Gy arm vs. 71.6 for the 78-Gy arm (p = 0.81), and the summary score mental health was 76.7 for the 68-Gy arm vs. 76.1 for the 78-Gy arm (p = 0.97). Statistically significant (p < 0.01) deterioration in QoL scores over time was registered in both arms in six scales. The deterioration over time was more pronounced in the high-dose arm for most scales. However, clinically relevant deterioration (>10 points) was seen for only two scales. None of the tested covariates were significantly correlated with QoL scores.

Conclusion

Dose escalation did not result in significant deterioration of QoL in prostate cancer patients. In both randomization arms, statistically significant decreases in QoL scores over time were seen in six scales. The deterioration of QoL was more pronounced in the physical than in the mental health domain and in some scales more in the high- than in the low-dose arm, but the differences between arms were not statistically significant.

Introduction

Prostate cancer has become the most frequent malignancy in men in Western countries. Beside definitive radiotherapy (RT), prostatectomy, and hormonal therapy (HT), observation might be applied in early-stage low-risk disease. Our group and others 1, 2, 3 have demonstrated that escalating the dose of RT not only improves tumor control but also increases late toxicity. The Dutch randomized trial (CKTO 96-10) has shown that freedom from failure at 7 years was significantly better in the 78-Gy arm compared with the 68-Gy arm (54% vs. 47%; p = 0.04). Although there was no difference in overall survival, late gastrointestinal (GI) toxicity was increased in the 78-Gy arm (p = 0.04) (3). Beside the achievement of cure as the primary goal of radical treatment of prostate cancer, toxicity and assessment of quality of life (QoL) have become very important secondary considerations, especially in view of the arguments in favor of watchful waiting.

To date, none of the randomized dose-escalation studies have thoroughly reported on the impact of dose escalation of RT on QoL by using validated QoL questionnaires.

The present analysis was undertaken within the framework of the Dutch randomized trial (CKTO 96-10) to assess the impact of dose escalation on QoL of prostate cancer patients treated with either 68 or 78 Gy using three-dimensional conformal RT techniques (3D-CRT). The analysis was done by intention to treat. We used a validated QoL questionnaire (SF-36) (4) to investigate the impact of increasing the dose of RT on QoL and the changes over time in different scales of SF-36 in these patients. Correlation of different independent covariates with QoL was also investigated.

Section snippets

Patients and Methods

Between June 1997 and February 2003, 669 patients with localized prostate cancer were enrolled in the Dutch trial (CKTO 96-10) and randomly assigned to receive either 68 or 78 Gy of 3D-CRT. The trial was carried out at four Dutch cancer institutions (3). Briefly, patients with localized prostate cancer with initial prostate-specific antigen (PSA) level ≤60 μg/L were eligible. Patients with low-risk disease, with lymphatic or distant metastases, and those having Karnofsky scores ≤70 were

Baseline patient characteristics

Of the 404 patients treated at the Erasmus MC–Daniel den Hoed Cancer Center, 300 patients (responders, 74%) have participated in the QoL part of the study, filling out at least one QoL questionnaire. There were no differences between responders and nonresponders with respect to age, tumor stage, PSA, adjuvant HT, or presence of comorbidity. More patients among responders had higher Gleason scores as compared with nonresponders (p = 0.005). Among the responders, patient characteristics were

Discussion

Several factors make the assessment of the impact of any treatment modality on QoL extremely important in patients with localized prostate cancer. First, most patients are asymptomatic, owing to the early diagnosis because of elevated PSA level. Second, there are several treatment modalities available, and watchful waiting is an alternative option for early-stage prostate cancer, especially in elderly men with a short expected life span. Third, patients may survive for a considerable period

Conclusion

Quality of life scores in prostate cancer patients as measured by the SF-36 questionnaire did not seem to be significantly decreased by escalating the dose of RT from 68 to 78 Gy. However, the decrease in QoL scores, in general, was more pronounced in the high-dose than in the low-dose arm and in the physical health than in the mental health domain. In both randomization arms, statistically significant decrease in QoL scores over time were seen in six scales, but the deterioration over time was

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Supported by the Dutch Cancer Society (Grants NKI 98-1830 and CKTO 96-10).

Conflict of interest: none.

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