This study is the first to examine changes in multiple dimensions of the symptom experience (i.e., occurrence, severity, and distress) for six of the most common symptoms reported by patients prior to, during, and following RT for prostate cancer. Whereas genitourinary and gastrointestinal symptoms were reported by 40% or more of these patients, four additional symptoms (pain, lack of energy, feeling drowsy, difficulty sleeping) emerged as significant clinical problems for these men with prostate cancer that are highly prevalent and are not well studied. Although fatigue is known to be a significant symptom during RT (29
), the potentially associated symptoms of feeling drowsy and difficulty sleeping are equally common, severe, and distressing to patients with prostate cancer during and after RT. These two symptoms may be more amenable to targeted interventions than fatigue and may reduce some of the fatigue reported by these patients. The finding of a relatively high prevalence of pain in these patients early in the course RT is important. Although the cause of the pain was not identified, the fact that nearly half of these patients reported its presence highlights the need for a thorough assessment and ongoing treatment of pain throughout the course of RT.
An evaluation of the trajectories for occurrence, severity, and distress for all six of the most common symptoms demonstrates that patient’s ratings across all three dimensions followed similar trends. Problems with urination and diarrhea were the only exceptions. Between weeks 17 and 25, occurrence and distress ratings related to problems with urination remained constant whereas severity ratings increased. The general trend for problems with urination (that is, an increase after treatment initiation with a subsequent decline) mirrors findings from previous studies (2
). The subtle finding, that distress related to problems with urination is correlated with occurrence rather than severity suggests that continued emotional support, even after treatment ends, is warranted, at least as long as symptoms persist.
Consistent with previous reports (3
), diarrhea increased in frequency during treatment and subsequently decreased, with similar trajectories for ratings of severity and distress. However, the use of piecewise modeling revealed that this particular cohort reported a delayed lesser yet significant increase in the symptom, between 17 and 25 weeks after treatment. The reason for this increase in diarrhea is unclear. One explanation may be that patients received more frequent follow-up and better symptom management for up to 17 weeks after treatment. An equally plausible explanation is that patients may have adhered to special diets until roughly that time. Generally speaking, it is proposed that as time since treatment lengthens and usual lifestyles resume, chronic side effects become more apparent. This new finding, that all three dimensions of this symptom had a delayed significant increase, is important because it changes the expected trajectory of treatment-related diarrhea and provides evidence that patients need more long-term symptom management support.
For all three dimensions, the trajectories of the other four symptoms studied (pain, lack of energy, feeling drowsy, difficulty sleeping) followed a similar pattern. Occurrence, severity, and distress were highest at baseline and decreased by roughly 5% with each additional week. No other study has reported a steady downward pain trajectory. Results of previous studies suggest that pain remains stable, increases, or varies depending on the type of RT received (3
). The reason that pain decreased over time in this study is unclear and warrants additional investigation.
Despite the fact that fatigue is known to be one of the most common and significant symptoms associated with RT, in this study, for all of the symptom dimensions the trajectories of lack of energy, feeling drowsy, and difficulty sleeping steadily improved over the course of treatment. Thomas et al. (18
) found the equally puzzling result that despite reporting fewer hours of sleep through six months after treatment, all other measures of sleep (i.e., trouble falling asleep, sleep adequacy, sleep latency) improved or remained constant over time. Taken together, these findings suggest the need for additional research on these symptoms.
Consistent with the findings for problems with urination and diarrhea in this study, in the three studies that evaluated the impact of functional status on urinary, bowel, and sexual function (5
), lower functional status was associated with worse symptom trajectories. No studies were found that evaluated the impact of functional status on other RT-related symptoms. In this study, the odds of reporting problems with urination, diarrhea, feeling drowsy, and difficulty sleeping at the beginning of treatment steadily increased as KPS score decreased. Interestingly, no association was found between the occurrence of pretreatment lack of energy and KPS score. Of note, baseline levels of symptom severity and distress had an inverse relationship with KPS score for all symptoms except pain. It is not entirely clear why KPS score affected only the baseline levels of these symptoms and not the trajectories of the various symptoms.
Ethnicity was found to have a significant interaction with only the occurrence of problems with urination between baseline and six weeks. Nonwhite patients were more likely than white patients to report an increase in problems with urination during this time. The reason for this finding is not entirely clear and warrants investigation in future studies.
It is interesting that none of the predictors evaluated affected any dimension of pain at baseline or the trajectories of pain. In contrast, pretreatment pain was predictive of occurrence of lack of energy, and occurrence and severity of problems with urination at baseline. Those patients with pretreatment pain experienced more rapid improvement in energy level over time. In addition, those patients with pretreatment pain had a less marked peak in problems with urination during treatment. These findings suggest that pain is not necessarily related to performance status and that better pain management, especially at the onset of treatment, may have a positive effect on symptom trajectories. Whereas Blesch et al. (32
) found that pain was highly correlated with fatigue in cancer patients, the relationship between pain and other symptoms in prostate cancer patients undergoing RT is virtually unexplored and warrants further investigation.
Consistent with previous reports (8
), no interactions were found between hormonal treatment prior to RT and problems with urination or diarrhea. However, patients who received hormonal treatment prior to RT were more likely to report the occurrence of and distress related to lack of energy over time than those who had not received hormonal treatment. This information can be used to educate patients about risk factors for fatigue. In addition, it is interesting that distress level followed the same trajectory as occurrence rather than severity. This finding suggests that any complaint of lack of energy should be taken seriously, regardless of severity.
It is notable that patients in this study did not report their symptoms to be more than moderately severe. Furthermore, for all time points, with the exception of problems with urination, the greatest likelihood that patients would report even slight symptom severity or mild symptom distress was only approximately 50% or 40%, respectively. These findings suggest, that during and after RT, clinicians must listen carefully for reports of difficulty with symptom management because patients with prostate cancer are not likely to rate their symptoms as severe or very distressing.
Many studies have explored the effects of RT on sexual function in patients with prostate cancer. In this study, problems with sexual interest or activity were not found to be one of the most common symptoms. One explanation for this finding is that perhaps not all patients were sexually active. This finding is important because it suggests that a greater number of patients would benefit from future research on symptoms that are more common and not as well characterized (e.g., pain, feeling irritable).
Limitations of this study include the relatively small sample size and high proportion of white patients. Future studies that include more ethnically diverse samples are needed to further explore the relationship between ethnicity and symptom trajectories. Because patients in this study had an initial KPS score of ≥ 60 and no metastatic disease, its results cannot be generalized to prostate cancer patients with lower functional status or more extensive disease. Although the trajectories of multiple dimensions of pain were evaluated, as well as how its presence at the initiation of RT affected the trajectories of other common symptoms, the causes of pain were not assessed. More detailed information on the causes and nature of pain in this population would be useful in the application of these findings to the clinical setting.
In summary, this study is the first to report on which six symptoms are the most common in men with prostate cancer who underwent RT. In addition, it is the first to simultaneously examine the trajectories of occurrence, severity, and distress for these symptoms in the same sample of patients. Through an evaluation of how a number of predictors influence these trajectories, we determined that lower KPS score at the initiation of RT leaves one more likely to report, with increased severity and distress, problems with urination, diarrhea, feeling drowsy, and difficulty sleeping at that time. It is remarkable that no predictors for pain were identified, including KPS score. The presence of pretreatment pain was the only predictor of the presence of lack of energy before treatment. This finding suggests that better pain control, regardless of treatment phase, may lead to improvements in fatigue. We were only able to examine the trajectories of the six most frequent symptoms in this population but there are a number of other common symptoms that warrant further attention. For example, it is notable that roughly one- third of the men in this study reported feeling irritable, having difficulty concentrating, and sweats. These symptoms are prime areas for future patient-centered research, and results of this study might be used by others to further prioritize efforts.