Long-term follow-up after active surveillance or curative treatment: quality-of-life outcomes of men with low-risk prostate cancer

In this paper, long-term patient reported QoL of men on AS, men who underwent RP or RT, and a reference group of men without prostate cancer was compared. Generic anxiety levels were similarly low for all four groups. In this observational study, for the first time, condition-specific function was measured with a single patient reported outcome measure (EPIC-26) across three treatment groups and a reference group without PCa. Statistically significant differences were found regarding urinary function and urinary incontinence with the AS group reporting better urinary function and less incontinence compared to the RP group. A statistically and clinically relevant (≥0.5SD) difference was found regarding sexual function. When comparing AS to RT, a statistically significant difference was seen regarding sexual function, with the AS group reporting better sexual function. This difference was, however, not clinically relevant. These observed differences in prostate-specific functioning between treatment groups could be expected, as AS has a less invasive character than RP and RT. Results furthermore indicate that the QoL of men on AS was very comparable to that of men without PCa.

Our data showed that only few men, i.e., 8% in the AS group, 12% in the RT and reference group, and 13% in the RP group, reported high levels of anxiety. There is a tendency to assume that men who choose AS and therewith live with untreated cancer, combined with the potential of missing the window of curability, will experience anxiety. Observational studies have shown results of AS cohorts in which anxiety levels are low [22, 23] versus studies in which anxiety levels of around 20% were seen [9, 24]. These observational studies involved selected groups of patients who chose to follow an AS strategy. In the recently published ProtecT trial, a randomized controlled trial in which men were randomly allocated to either active monitoring, RP or RT, longitudinal 5 year follow-up results were presented. With respect to anxiety, measured through the Hospital Anxiety and Depression Scale (HADS), no significant differences among the treatment groups were seen (p = 0.27), suggesting that men on AS are not more anxious than men on RP or RT [25]. This might indicate that psychological support is less needed for men on AS. However, it should be noted that only 62% (1643/2664) of eligible men underwent randomization in the ProtecT trial, while 38% selected their own treatment (based on own or urologist preferences). Furthermore, men who were randomized to active monitoring had regular contact with a specialist nurse with whom any concerns could be discussed. Furthermore, our data confirm the results that Bellardita et al. describe in their review study [8], summarizing findings of mainly short-term studies.

Although the RP group reported frequent urinary incontinence and both RP and RT groups reported limited sexual function, they reported similar levels of bother as the AS and reference groups, with the latter reporting hardly any urinary incontinence and better sexual functioning. The pattern of impaired function but no related bother can possibly be explained by response shift [26, 27]. Sprangers and Schwartz describe response shift as “a change in the meaning of one’s self-evaluation of QoL as a result of a change in one’s internal standards of measurement (i.e., recalibration), the importance attributed to component domains constituting QoL (i.e., change in values), or construal of the meaning of QoL (i.e., concept redefinition) [26, 28].” It may be that over time men have accepted the changes in, e.g., their sexual functioning, because they perceived these as an inevitable consequence of PCa treatment; a condition thought to be life threatening by at least a part of men with PCa [27, 29]. As a result, men may have changed the importance they attach to sexual activity to soften the negative influence of deteriorating sexual function (i.e., change in values) [28]. Behavioural scientists tend to refer to the response shift process as cognitive adaptation [30, 31]. Ageing may play a role as well [32]. In addition to the higher prevalence of erectile dysfunction in older men, Korfage et al. found that diminishing sexual activity with increasing age was considered more or less normal amongst a group of treated PCa patients [27, 33].

While patients are often able to adapt to a new situation and accept side-effects, it is important to enable them to consider potential consequences of treatment beforehand. We want to provide relevant PCa treatment information, and therewith enable men to base their treatment-choice on what they consider important and to avoid those side-effects they find least acceptable. The here presented outcomes for the three treatments can support men and their physicians in deciding what treatment fits the patient best in terms of QoL. By discussing, amongst others, the side-effects of each type of treatment as well as patients’ preferences, we furthermore hope to stimulate shared decision-making between patients and physicians, as patient participation may positively affect treatment decision-making. A recent study amongst 1529 men with clinically localized PCa explored whether active patient involvement in decision-making and greater patient knowledge are associated with better treatment decision-making experiences and QoL [34]. The authors concluded that the men who were knowledgeable about PCa and the side-effects of treatment at the time of treatment decision-making experienced better QoL 6 months after treatment because of realistic expectations regarding side-effects [34].

This study has limitations. Differences related to baseline clinical and demographic characteristics of the participants were seen. Because men were not randomized into treatment groups, clinical and demographic characteristics slightly varied per group. However, the study design we report does represent current clinical practice, where choice for treatment is selective and individualized. Our findings furthermore highlight the importance and need of a baseline, i.e., pre-diagnostic biopsy, measurement. Future studies, such as the mixed-method study by Ruane-McAteer et al. [35], will, by including such a baseline measurement, provide further valuable information on the impact on QoL of either AS or direct curative treatment on both mental and physical health of the patient. The RT group in our study is heterogeneous. As we acknowledge that there is a difference between brachytherapy and external radiation, we stratified QoL outcomes in the individual radiotherapy groups (i.e., mono brachytherapy and brachytherapy followed by external radiation and Cyberknife) in appendix Table 4. When comparing mono brachytherapy with brachytherapy + external radiation, mainly, a difference on the sexuality domain was seen with the mono brachytherapy group showing better sexual function. In comparing the brachytherapy + external radiation and Cyberknife groups, significantly higher bowel domain scores were seen for the Cyberknife group indicating better bowel function in the latter group. We furthermore chose an age-matched cohort of screening arm participants without PCa from the ERSPC Rotterdam study to reflect the general population. The previous studies have shown that ERSPC-Rotterdam participants differ from the general population, in the sense that they seem to be healthier [36, 37]. However, the entire RP group, 20% of the AS group, and 37% of the RT group also participated in ERSPC Rotterdam. Strengths of our study are the considerable length of follow-up of 4–10 years, the good questionnaire response rates, the use of one validated patient reported outcome measure—the EPIC—to compare prostate-specific function across all four groups, the inclusion of a non-PCa reference group, and, for the first time, the reporting of long-term QoL results for an AS cohort.

To conclude, in this cross-sectional study, we compared long-term QoL of PCa patients on AS to that of PCa patients who followed direct curative regimens and a reference group of men without PCa. Generic anxiety was similarly low amongst all four groups and in terms of prostate-specific functioning, the AS group reported better sexual function as compared to the RP and RT groups and better urinary function than the RP group. The QoL of men on AS was very comparable to that of men without PCa. Our results indicate men who followed an AS strategy for a long-term period were not anxious and accepted it well, suggesting that AS may be a good treatment option for men with low-risk PCa.