High dose rate brachytherapy boost for localized prostate cancer : clinical and patient-reported outcomes

Curative treatment of prostate cancer is controversial. The therapeutic effects of surgery and radiotherapy (RT) have hitherto proved to be similar, why other endpoints such as health related quality of life (HRQoL) stay important in decision-making.

The aims of this thesis were to evaluate clinical and patient-reported outcomes after combined external beam RT and high dose rate (HDR) brachytherapy boost including neoadjuvant androgen deprivation therapy (ADT). Four samples from a cohort of 870 consecutive patients treated 1998-2003 at the Department of Oncology, Karolinska University Hospital, were studied.

Longitudinal studies of HRQoL after combined RT are scarce. Using the EORTC QLQ-C30 and PR25 questionnaires, short-term HRQoL was prospectively assessed twice in 80 patients at an 18 month interval 0- 18 months after RT. Analysis included 2 subgroups of relapse-free patients in order to detect differences in acute and late reactions. The levels of HRQoL were generally high, did not change over time and were in large comparable to normative data. Urinary, bowel and sexual HRQoL outcomes corresponded to known acute and late effects of radical RT and ADT. Effects of ADT seemed to be substantial but mostly transitory.

Self-reported urinary, bowel and sexual side effects were investigated prospectively at the outpatient clinic, Radiumhermmet, at multiple assessment points before and 2-34 months after combined RT by means of a prostate-specific questionnaire. 525 patients responded to at least one questionnaire. Baseline sexual function was reported statistically significantly worse in patients receiving ADT. Urinary, bowel and sexual problems increased after RT and persisted at higher levels compared to baseline. Though there were signs of hormonal restitution, erectile dysfunction persisted. Side effects seemed comparable with those of other RT series.

Late HRQoL more than 5 years after RT was evaluated in 158 patients, using the EORTC QLQ-C30 and PR25 questionnaires. In comparison with normative data, minor differences in general HRQoL were demonstrated, possibly suggesting "response shift" effects. Longitudinal analysis of discase-specific HRQoL showed that urinary urgency, increased stool frequency and erectile problems persisted five years after treatment. Few signs of hormonal disturbances were noted. The frequency of late rectal bleeding was low. Fecal incontinence was reported by 25% of patients of which 80% considered it to be a minor problem.

A survival analysis included 154 patients. The 5-year relapse-free survival was 84%, comparable to other published series. No local recurrence was seen. Median PSA was non-measurable. 68% of patients staged T3 were relapse-free. In multivariate Cox regression, WHO grade statistically significantly influenced outcome (HR 2.46 95% Cl 1.44-4.18). Using nomograms, predicted 5-year relapse-free survival rates for surgery and RT were 54% and 70 % respectively. Late RTOG grade 3 toxicity developed in 1% (bowel) and 4% (urinary) of patients.

In conclusion, combined RT provides high cure rates, but entails a risk of side effects of which most seem to be of limited duration.

List of scientific papers

I. Wahlgren T, Brandberg Y, Haggarth L, Hellstrom M, Nilsson S (2004). Health-related quality of life in men after treatment of localized prostate cancer with external beam radiotherapy combined with (192)ir brachytherapy: a prospective study of 93 cases using the EORTC questionnaires QLQ-C30 and QLQ-PR25. Int J Radiat Oncol Biol Phys. 60(1): 51-9.
https://doi.org/10.1016/j.ijrobp.2004.02.004

II. Wahlgren T, Nilsson S, Ryberg M, Lennernas B, Brandberg Y (2005). Combined curative radiotherapy including HDR brachytherapy and androgen deprivation in localized prostate cancer: a prospective assessment of acute and late treatment toxicity. Acta Oncol. 44(6): 633-43.
https://doi.org/10.1080/02841860510029716

III. Wahlgren T, Nilsson S, Lennernäs B, Brandberg Y (2006). Promising long-term health related quality of life after high dose rate brachytherapy boost for localized prostate cancer. [Submitted]

IV. Kälkner KM, Wahlgren T, Ryberg M, Cohn-Cedermark G, Castellanos E, Zimmerman R, Nilsson J, Lundell M, Fowler J, Levitt S, Hellström M, Nilsson S (2006). Clinical outcome in patients with prostate cancer treated with external beam radiotherapy and high dose-rate 192-Iridium brachytherapy boost: A 6-year follow-up. Acta Oncologica. [Accepted]
https://doi.org/10.1080/02841860601156140