Prostate cancer (PC) is a major health problem in men in the Western world. Definitive treatment options for localized PC routinely include radical retropubic prostatectomy (RP), external beam radiotherapy (EBRT), and brachytherapy or a combination of these methods. A recent review of 18,000 studies compared the outcomes of curative treatment of localized PC in the post-PSA era (1), and it was concluded that randomized studies are rare and there is a lack of evidence to determine whether any of the available treatment options are superior for prolonging survival. Therefore, it is necessary for patients to consider the morbidity and side-effects of the treatment modalities when deciding on treatment for PC. This underlines the importance of having detailed knowledge of health-related quality of life (HRQoL) and adverse events associated with different curative treatments. Early HRQoL research concerning treatment-related side-effects such as incontinence, bowel disturbances, and impact on sexual activity showed disparate profiles for the various treatment modalities (2–4). In the cited investigations, patients treated with RP reported more incontinence, which was acute but improved over the first 2 years after treatment. By comparison, bowel problems were worse in irradiated patients, continuing for up to 4 years, and urinary bother was increased in patients treated by brachytherapy with permanent implants. HRQoL studies concerning sexual problems have reported fewer initial problems after brachytherapy and EBRT than after RP, but the results are often hampered by a lack of baseline data.

During the 1990s, questions were raised about whether the traditional EBRT treatment dose of 66–70 Gy was sufficient to cure PC. Since then, several studies have shown increased disease-free survival after dose escalation (5). Such amplification can be done by several different methods: three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and combinations of these approaches with high-dose-rate brachytherapy (HDRBT), low-dose-rate brachytherapy or particle beam boosts. Some studies have compared acute effects of traditional and modern dose-escalated radiotherapy on HRQoL in PC patients (6,7), and the results indicated comparable HRQoL outcomes. However, few investigations have examined long-term effects in this clinical context.

The aim of the present study was to compare long-term HRQoL in men who were diagnosed with PC between 1988 and 1997 and had undergone one of the two curative treatment strategies that, with small adjustments, are still in routine use today. Our focus was on HRQoL after external beam radiotherapy combined with high-dose-rate brachytherapy (HDRBT-EBRT) and open retropubic prostatectomy (RP).

The initial cohort comprised 492 patients, but 71 (14.4%) of those individuals died before onset of the study. Thus, 421 patients were asked to participate in the HRQoL evaluation; 347 (82%) completed the questionnaires, and 42 declined to take part or did not respond. The initial number of patients in each treatment group, the number of respondents, and the number of deaths before administration of the questionnaires are listed in Table I.

Clinical and demographic patient characteristics for each treatment group are presented in Table II. There were no statistically significant differences in clinical parameters between the groups, except regarding T stage and PSA recurrence at the time of the questionnaires. The proportion of patients with locally advanced disease (T3–T4 tumors) was larger in the HDRBT-EBRT group than in the RP group (13 and 6%, respectively; P=0.01). PSA relapse at the time of the questionnaires was noted in 44% of the men in the RP group compared to 9% in the HDRBT-EBRT group (P<0.0001). All demographic parameters except education were equally distributed between the treatment groups.

HRQoL results for the normative population and the treatment groups are shown in Fig. 1. In general, the patients’ mean HRQoL scores were high and similar to the mean scores for the normative sample, with the exception of physical and role function, for which the patients’ scores were higher. Considering physical symptoms, compared to the normal population, the patients reported less pain but more pronounced problems with sleep disturbances.

The results of the univariate and multivariate analyses comparing the two treatment groups are outlined in Table III. Taking into account age, PSA recurrence, and neo-adjuvant hormonal treatment, there were no statistically significant differences between the groups in either the univariate or the multivariate regression analysis of the functional domains in the EORTC QLQ C-30 questionnaire. Adding ‘risk group at diagnosis’ or ‘time from diagnosis to time for questionnaire’ as confounding factors did not change the results (data not shown). Concerning the symptom scale, a higher level of problem with diarrhea was found in the HDRBT-EBRT group, and this difference was both statistically and clinically significant. Small clinically significant differences favoring the RP group were found for global quality of life, role functioning, fatigue, dyspnea, insomnia and diarrhea, but none of these differences were statistically significant.

Results concerning the disease-specific and treatment-related symptoms are presented in Table IV. Levels of bowel-related symptoms and urinary problems were higher in the HDRBT-EBRT patients than in the RP patients, and these results were statistically significant but the clinical significance were small. There was no statistically significant difference in sexual activity between the two treatment groups, although only 37% of the patients reported that they were sexually active and sexual function was low (mean score 57, SD 25).

Clinically localized PC can be treated effectively by use of conceptually different treatment approaches with contrasting patterns of acute and late side-effects. Hence overall and disease-specific HRQoL following treatment has become an important aspect in patients with such disease. In general, the studies published to date concern HRQoL during the first 3–5 years after treatment. The number of longer follow-ups is limited, and, in particular, few investigations have compared late effects of surgery and modern dose-escalated radiotherapy.

The present cross-sectional cohort study explored long-term HRQoL in PC patients 7 years after curative treatment by two different methods, RP and HDRBT-EBRT. The results were compared with age-matched HRQoL data on the normal male population in Sweden. We found that the levels of overall quality of life were high, irrespective of curative treatment modality. In short, the scores were high on functional scales and low on symptom scales in all domains, and they concurred with age-adjusted normative data. The data from the disease-specific questionnaire revealed a small but statistically significant difference in bowel and urinary problems between the treatment groups, in favor of the RP group.

The differences we observed between the study groups agree with the findings of other investigators concerning general HRQoL in PC patients following curative treatment (17–20). In the disease-specific EORTC QLQ-PR25 instrument, more bowel and urinary tract symptoms were reported by patients in the HDRBT-EBRT group than by those in the RP group. Similar results concerning bowel symptoms have been reported by other researchers (3,17–20). These studies also revealed a pattern of increased urinary problems and incontinence in RP patients, but more extensive urinary bother (e.g., urgency and frequency) among irradiated patients, especially those treated with permanent seeds. HRQoL data on the combined HDRBT-EBRT treatment are limited. However, similar to our findings, a study of HRQoL 5 years after treatment in a cohort of PC patients given HDR brachytherapy and EBRT indicated that urinary symptoms were more common than bowel symptoms (21). The authors suggested that the standard strategy applied at the time of their investigation (i.e., assuming that a central position of the urethra represents a good estimate of the location of urethra, when defining the treatment dose) might have led to administration of higher doses to the urethra than intended and hence affected the incidence of treatment-induced chronic urethritis. A similar technique was used in Gothenburg in the 1990s, which might explain the difference observed in the present study. Moreover, other investigators (19) have reported that urinary and bowel symptoms, as well as sexual problems, are increased after radiotherapy combined with NHT.

Only about one third of the patients in our study were sexually active, and no differences in sexual function were found between the treatment groups. The interpretation of the results in this domain was limited by lack of individual baseline data and data on the normal population. Our analyses were also restricted by the small sample size with respect to this variable. In a comparison of men treated with EBRT, permanent seed implants, and RP, Litwin et al (18) noted that the EBRT group reported superior sexual function after 24 months compared to the other groups. However, severe sexual problems were experienced to the same extent in all groups, regardless of treatment. Other studies of HRQoL have demonstrated a general decrease in sexual function after 3–5 years of follow-up in patients treated with RP and EBRT (2019).

The differences we observed between the patient cohort and the normal population agree with the results of a 5-year follow-up investigation of HRQoL in Swedish PC patients (20), which showed that the patients had better physical and role function and lower levels of pain compared to men in the normal population. An explanation for this might be that the PC patients based their questionnaire responses on different standards compared to the non-PC subjects, a phenomenon that has been referred to as ‘response shift’ (22).

Limitations of the present study include the lack of baseline HRQoL assessment and the lack of randomization to treatment, thus, it is possible that confounding factors affected the results. Although, the RP and the HDRBT-EBRT groups were equivalent regarding the majority of clinical parameters previously shown to be relevant, there was a striking difference between the two groups concerning the PSA recurrence rate at the time of the questionnaires (44 and 9%, respectively). A plausible explanation for this discrepancy is that different definitions of PSA recurrence were applied in our study depending on the treatment modality used: for RP, PSA ≥0.2 ng/ml; for HDR-EBRT, PSA ≥2 ng/ml above nadir. The present study was performed in the early 2000s, at which time RP and dose-escalated radiotherapy were the standard treatment options for localized PC. Technically, both the open RP and the HDRBT-EBRT are still performed in manners similar to those that were employed during the study period. Therefore, our results can provide physicians and PC patients with valuable information concerning long-term effects on HRQoL after treatment of PC, which is particularly important considering that few investigations have compared long-term HRQoL after RP and dose-escalated radiotherapy.

The present study also had several strengths. First of all, it was large, population based, and had a high overall response rate (82%). Furthermore, the public health system in Sweden offers a unique opportunity to follow patients over long periods, and thus, potential inter-individual differences in staging, grading, treatment procedures, and follow-up during the study period were at a minimum in our investigation. Another advantage is that two validated questionnaires were used in our evaluation, one of which is disease specific, and age-adjusted normative data were available.

In conclusion, we found that long-term HRQoL after curative treatment of localized PC by RP or HDRBT-EBRT was high and agreed with age-adjusted normative data. Statistically significant differences in bowel and urinary symptoms were observed in favor of the RP group, but the clinical significance concerning these disparities was small.