- Email: [email protected]
The physical burden of prostate cancer
Urol Clin N Am 30 (2003) 305–313
The physical burden of prostate cancer David F. Penson, MD, MPHa,b,*, Mark S. Litwin, MD, MPHc a
VA Puget Sound Health Care System, Section of Urology, 112-UR 1660 S. Columbian Way, Seattle, WA 98108, USA b University of Washington School of Medicine, Box 356510 Seattle, WA 98195, USA c Department of Urology, UCLA School of Medicine, 66-124 CHS Box 951738, Los Angeles, CA, 90095-1738, USA
Prostate cancer remains the most frequently diagnosed solid tumor and the second leading cause of cancer death among American men. In 2001 alone, the American Cancer Society projected over 198,000 new diagnoses and 31,500 deaths from prostate cancer [1]. The sheer volume of prostate cancer cases represents a tremendous burden of disease that will probably increase in the future, primarily because patients are being diagnosed at a younger age and are living longer with their disease. Historically, prostate cancer has been considered a disease of elderly men. In the past decade, however, there has been a steady decrease in the average age at diagnosis [2] resulting at least in part from the introduction of serum prostate-specific antigen (PSA) testing. In fact, the largest increase in prostate cancer incidence during the PSA era, which began in the early 1990s, has occurred in men under age 65 years [2]. Recent data from the Seattle-Puget Sound Surveillance, Epidemiology and End Results (SEER) cancer registry for the period from 1995 to 1999 indicate that 33% of all incident prostate cancer cases are now diagnosed in men under age 65 years. The shift toward earlier age at diagnosis means that prostate cancer survivors will have longer life expectancies after diagnosis, regardless of treatment, and will therefore have more time to experience the physical, psychologic, and economic burdens of this highly prevalent malignancy.
* Corresponding author. VAPSHCS Section of Urology, 112-UR 1660 S. Columbian Way, Seattle, WA 98108. E-mail address: [email protected] (D.F. Penson).
In prostate cancer, the physical burden in particular can be onerous for the patient. Although there are many obvious examples of this burden, such as pain from metastatic bony lesions or discomfort caused by lower urinary tract symptoms from outlet obstruction, there are less apparent long-term effects of therapy that can cause significant physical problems for patients as well. All these physical effects of prostate cancer can profoundly affect quality of life. The shift toward earlier age at diagnosis means that prostate cancer survivors will have longer life expectancies after diagnosis, regardless of treatment, and will therefore have more time to experience the physical, psychologic, and economic burdens of this highly prevalent malignancy. This article provides a comprehensive description of the physical burden of both metastatic and localized prostate cancer and the associated treatments. Information in this report will be helpful for describing to patients the long-term effects of prostate cancer and its therapy and will aid in clinical decision-making while helping patients set reasonable expectations.
Assessing the physical burden of prostate cancer The physical impact of prostate cancer can profoundly affect quality of life. Therefore, one method of assessing the physical burden of this condition is to study health-related quality of life (HRQOL) in men with prostate cancer. Healthrelated quality of life involves patients’ perceptions of their own health and ability to function in life [3]. The concept of HRQOL includes not only functional status and symptoms of a given disease or treatment but also the degree of problems or
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difficulty that patients experience from their condition [4]. Health-related quality of life is a patient-centered variable, measured using questionnaires (also known as instruments) that are administered directly to patients in an objective manner. The principles of psychometric test theory are used to design instruments that reproducibly and accurately quantify HRQOL [5]. Healthrelated quality-of-life instruments typically contain questions, or items, that are organized into scales. Each scale measures a different aspect, or domain, of HRQOL. Typically, the items in a scale are combined to generate a numerical summary score for a particular domain; this score can then be used in statistical analyses. A number of established and validated HRQOL instruments have been specifically developed for men with prostate cancer. These instruments include the University of California, Los Angeles Prostate Cancer Index (UCLA PCI) [6,7], the Expanded Prostate Cancer Index Composite (EPIC) [8], the Functional Assessment of Cancer Therapy-Prostate (FACT-P) [9,10], and the Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) [11,12]. For more detail on the methodology of HRQOL measurement and the available instruments for assessing quality of life in prostate cancer, the reader is referred to the authors’ previous publication on this topic [13].
The physical burden of metastatic prostate cancer Given the predilection of prostate cancer to metastasize to bone as it advances, it is not surprising that patients with metastatic prostate cancer suffer a significant physical burden of disease that affects quality of life. Investigators have shown that as prostate cancer progresses, HRQOL worsens accordingly. For example, one study found that patients with hormone-resistant prostate cancer have worse outcomes than men with hormone-sensitive disease in the following HRQOL domains: role functioning (mean score= 63 versus 88); physical functioning (60 versus 85) and global quality of life (49 versus 74) [14]. Similarly, Kim et al [15] noted that among patients treated for metastases, those with progressive disease seemed to have worse quality of life than those with stable disease, particularly for pain, fatigue, sleep, and physical and role functioning. Although these studies demonstrate that the physical burden of metastatic disease and its impact on quality of life worsen as the disease progresses, other researchers have shown that the negative
effect of advancing disease on HRQOL can be reversed with appropriate treatment. For example, Albertsen et al [16] studied metastatic prostate cancer patients in remission treated with luteinizing hormone-releasing hormone (LHRH) agonists and flutamide and found that their general HRQOL was indistinguishable from an age-matched control population of men without prostate cancer. Taken as a whole, these studies indicate that advanced prostate cancer has a significant effect on the physical domains of HRQOL and that these effects can be reversed with administration of hormone ablation therapy in appropriate cases. Although hormone ablation therapy can improve HRQOL in men with symptomatic advanced prostate cancer, its role in asymptomatic patients with advanced disease is less clear. A number of studies now provide preliminary evidence that early hormonal therapy may prolong survival in men with asymptomatic advanced disease [17–19]. There is still considerable debate as to the optimal time to initiate therapy in these patients [20], because hormone ablation has a number of physical side effects that may affect HRQOL. Herr and O’Sullivan [21] compared patients receiving hormonal therapy versus observation for asymptomatic advanced disease. Although there may have been significant selection bias because of the observational nature of the study, patients who elected to defer treatment had better HRQOL than those who opted for early intervention. In particular, men who received early therapy experienced significantly more fatigue and hot flashes that affected quality of life than those who delayed treatment. This report confirmed findings from a similar, earlier study from the same group [22]. These data indicate that, when discussing immediate versus deferred hormone ablation therapy for asymptomatic advanced prostate cancer, patients and providers must carefully weigh the possible survival benefit against the physical side effects of early treatment and their impact on HRQOL. Once patients elect to receive treatment for metastatic prostate cancer, there is little difference in HRQOL outcomes between men undergoing medical versus surgical castration. Litwin et al [23] identified no differences in any of the general or disease-specific domains of the RAND 36 Item Health Survey (SF-36) or the UCLA Prostate Cancer Index when comparing men who underwent orchiectomy and those receiving combined androgen blockade. In a similar study, Cassileth et al [24] questioned 159 men who underwent
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either medical or surgical castration for advanced disease and found no difference in satisfaction with treatment choice 3 months after initiation of therapy. Although the method of castration does not seem to have a significant impact on HRQOL, the presence or absence of additional androgen-blocker therapy does influence HRQOL. In a clinical trial of 739 men with stage M1 prostate cancer, patients randomly assigned to treatment with orchiectomy plus flutamide reported significantly more diarrhea than those who were randomly assigned to orchiectomy plus placebo [25]. The negative impact on HRQOL of the gastrointestinal side effects of androgen-receptor blockade may be less in patients receiving bicalutamide [26]. Because hormone ablation therapy has a significant effect on HRQOL, there has been an increasing interest in the potential role of bicalutamide monotherapy in the initial treatment of advanced prostate cancer. Studies have shown that patients who receive antiandrogen monotherapy have fewer sexual side effects than those who receive hormone ablation therapy. Boccardo et al [27] randomly assigned 220 men with advanced disease to receive either bicalutamide alone or combined androgen blockade. They found no difference in progression-free or overall survival (median follow up, 38 months), and the bicalutamide monotherapy group was noted to have better libido and erectile function (P ¼ 0.01 and 0.002, respectively) than the group treated with combined androgen blockade. In a similar study, Chodak et al [28] randomly assigned 486 men to receive either antiandrogen monotherapy or castration. As in the earlier study, these investigators found that the monotherapy group had better sexual interest and function than the castration group. These studies demonstrate that antiandrogen monotherapy may be a reasonable alternative to traditional hormone ablation regimens. Unfortunately, these studies do not provide long enough follow up to determine how the therapies compare in terms of survival. Intermittent hormone ablation therapy has also been popularized as a possible alternative in the treatment of advanced, hormonally sensitive prostate cancer, because it may result in better quality of life with minimal, if any, difference in overall survival. Bouchot et al [29] prospectively assessed HRQOL outcomes in 43 men with symptomatic, advanced prostate cancer treated with an intermittent hormone ablation regimen. They noted that, after initiation of hormonal ablation therapy, these patients had significant improvement in bony pain and urologic symptoms. When the patients went
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into an off-treatment period, urologic symptoms often recurred, whereas bony pain did not. Although these studies are promising, additional research is needed to identify clearly novel ways to minimize the physical impact of hormonally naive, metastatic prostate cancer and its treatments. Men with hormone-resistant prostate cancer have worse quality of life than those with hormone-sensitive disease. A number of studies have documented that various chemotherapeutic agents improve HRQOL in men with hormone-resistant disease. For example, Osoba et al [30] assessed HRQOL in 161 men randomly assigned to receive prednisone alone versus prednisone and mitoxantrone over a 26-week follow-up period. At 6 weeks, patients taking prednisone alone showed no improvement in HRQOL scores, whereas those taking mitoxantrone plus prednisone showed significant improvements in global quality of life (P=0.009) and in four functional domains (P < 0.01). In the crossover arm of the study, the addition of mitoxantrone to prednisone after failure of prednisone alone was associated with improvements in pain, pain impact, pain relief, insomnia, and global quality of life (P < 0.003) After 18 weeks of therapy, those receiving mitoxantrone plus prednisone continued to improve in 11 of the 14 function and symptom scales used to measure HRQOL. This study and others [31,32] demonstrate that palliative chemotherapy can lessen the physical burden of prostate cancer in men with advanced, hormone-resistant disease. Although these treatments may not prolong life expectancy, a documented quality-of-life advantage for a given treatment will result in benefit to the patient and should be strongly considered when choosing therapies.
The physical burden of localized disease Untreated disease When patients and providers think of the physical burden of localized prostate cancer, they tend to focus on the well-known side effects of aggressive treatment–impotence and incontinence [33]. Localized prostate cancer in and of itself can cause significant lower urinary tract symptoms (LUTS) and other physical problems if left untreated. Unfortunately, few studies have examined the quality-of-life impact of localized disease managed expectantly. Jonler et al [34] assessed HRQOL in 52 consecutive patients who elected watchful
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waiting and deferred treatment for localized prostate cancer. Over a median follow up of 3.3 years, 31% required transurethral resection of the prostate gland for LUTS or acute urinary retention. Patients in the study reported a high incidence of dripping at least some urine daily (37%), pad use (21%), problematic urinary incontinence (21%), and urethral strictures (21%). Thirty-five percent reported that they were bothered by their prostate cancer or by additional treatment they had received. This study indicates that localized prostate cancer has an independent physical impact on quality of life that often creates problems for patients. This is important information that providers and patients should consider if they are considering conservative management of localized prostate cancer. The physical impact of aggressive therapies on quality of life Currently, the most commonly used treatment modalities for localized prostate cancer include radical prostatectomy, external beam radiotherapy, and interstitial brachytherapy. All these treatments have side effects that can profoundly affect patients’ sexual, urinary, and bowel function. Numerous studies have looked at larger issues such as long-term physical function and bodily pain and have found no differences among these treatments. Litwin et al [7] compared general HRQOL in 214 men undergoing prostatectomy, radiotherapy, or conservative management and found no significant differences between the groups. Lim et al [35] and Shrader-Bogen et al [36] performed similar studies and noted no differences in general HRQOL among treatments. More recently, Sanchez-Ortiz et al [37] studied 171 patients who underwent either palladium or iodine interstitial brachytherapy and found no differences in general HRQOL outcomes between the two radiation sources. Although the aggressive therapies lead to similar outcomes in terms of general physical function, they differ significantly in long-term sexual, urinary, and bowel function following treatment. Sexual function Of the three aggressive therapies commonly used for treatment of localized prostate cancer, radical prostatectomy (RP) is commonly thought to have the highest incidence of post-treatment sexual dysfunction. Stanford et al [38] reported longitudinal quality of life outcomes of 1291 men who underwent RP for localized disease from the
Prostate Cancer Outcomes Study (PCOS), a population-based cohort of men diagnosed with prostate cancer from 6 geographic regions within the SEER program of the National Cancer Institute. At baseline, 73% of men reported erections firm enough for sexual intercourse, and 45% of men reported no difficulty in maintaining an erection. At 2 years following surgery, 19% of men reported erections firm enough for intercourse, and 7% of men reported no difficulties maintaining an erection. When asked how big a problem their sexual function was at 2 years following surgery, 14% said it was no problem, 23% said it was a small problem, and 42% said it was a moderate to big problem. This study demonstrates that patients have a significant amount of sexual dysfunction following surgery and that this dysfunction affects quality of life, because a considerable number of patients experience bother from their symptoms. It is important to note, however, that the degree of dysfunction and bother do not correlate as well one might expect, indicating that the effect of erectile dysfunction on patients’ quality of life is variable and highly idiosyncratic. The use of the nerve-sparing radical prostatectomy technique is purported to improve potency following surgery for localized prostate cancer. Studies examining quality-of-life outcomes following nerve-sparing prostatectomy have been mixed, however. Talcott et al [39] compared HRQOL outcomes in 28 men who underwent non–nerve-sparing radical prostatectomy with 66 men who underwent either unilateral or bilateral nerve-sparing surgery at a single institution. They found that men who underwent any type of nervesparing procedure had worse sexual function than had been previously reported and found no statistically significant differences in sexual functioning between the groups receiving nerve-sparing and non–nerve-sparing procedures. Using a multicenter observational disease registry, Litwin et al [40] studied 218 men who underwent nervesparing radical prostatectomy and 124 men who underwent the non–nerve-sparing technique. They found that the patients who underwent nerve-sparing surgery had significantly better sexual function than those who had non–nervesparing surgery at 6, 12, and 18 months following treatment, although the overall level of sexual function was low for both groups. Given the multi-institutional nature of this study, these results probably better represent the effectiveness of nerve-sparing surgery in the general population.
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Significant sexual dysfunction can occur after both external beam radiotherapy and interstitial brachytherapy as well. In a study of 287 men who underwent conformal external beam radiation therapy for localized prostate cancer, Mantz et al [41] noted actuarial potency rates of 96%, 75%, 59%, and 53% at 1, 20, 40, and 60 months after therapy, respectively. Other studies have shown that, similar to the situation following surgery, the effect of erectile dysfunction on quality of life is highly individualized. Hamilton et al [42] studied the impact of external beam radiotherapy on 497 men from PCOS, a population-based cohort of patients with localized prostate cancer. They found that 43% of men who were potent before diagnosis were impotent 2 years after radiotherapy, but more than two thirds of these men were satisfied with their treatment and would choose the same option again, indicating that their sexual dysfunction was not a great problem for them. Fowler et al [43] studied 432 Medicare patients who underwent external beam radiotherapy and found that only 37% reported that their sexual function was a ‘‘medium or big problem,’’ although the amount of erectile dysfunction was no doubt higher than that. Helgason et al [44] studied 53 men who had undergone external beam radiotherapy for localized prostate cancer and noted that 77% reported diminished sexual desire, 34% reported erections insufficient for intercourse, and 77% reported some loss of stiffness. More importantly, 50% of men reported that their overall quality of life had decreased much or very much as a direct result of decreased erectile function. Clearly, sexual dysfunction is a relatively common occurrence after external beam radiotherapy, although, as after surgery, it may or may not be a significant problem for the patient. Finally, erectile dysfunction can also occur after interstitial brachytherapy. Brandeis et al [45] found that, at 3 to 17 months following treatment, sexual function in the brachytherapy group was significantly worse than in age-matched controls. Other studies have also noted that sexual function following brachytherapy is worse than that of agematched controls [46]. To quantify the degree of sexual dysfunction following this treatment, Krupski et al [47] studied HRQOL in 70 patients who received isolated brachytherapy for localized disease and found that at 3, 6, and 9 months following treatment, patients had an approximately 25%, 40%, and 55% probability of being able to achieve penile erection adequate for sexual intercourse. In another study, Talcott et al [48]
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reported a 44% incidence of complete impotence in men who had undergone brachytherapy with varying degrees of follow up following treatment. Further research with longer-term follow up is needed to understand better the impact of erectile dysfunction on quality of life in brachytherapy patients. These studies demonstrate that, like other aggressive treatment for localized prostate cancer, brachytherapy commonly results in erectile dysfunction that can affect HRQOL and represents a significant physical burden for patients with this disease. Urinary function Urinary dysfunction is also common after aggressive therapy for localized prostate cancer, although the type of dysfunction depends on the treatment received. Patients who undergo radical surgery are more likely to report stress urinary incontinence, whereas men undergoing either external beam radiotherapy or interstitial brachytherapy often experience significant irritative voiding symptoms [42,49,50]. Although the type of urinary dysfunction differs among treatments, the impact on HRQOL is considerable with both surgery and radiotherapy and represents a significant burden of disease for patients. Radical prostatectomy is associated with a significant incidence of postoperative side effects, including stress urinary incontinence and bladder neck contractures that can cause obstructive voiding symptoms and urinary retention. A recent publication from the Prostate Cancer Outcomes Study, a population-based cohort of men with prostate cancer, reported on longitudinal qualityof-life outcomes in 1291 men who underwent radical prostatectomy [38]. Two years after surgery, 32% of the men reported total urinary control, 40% reported occasional leakage, 7% reported frequent leakage, and 2% had no urinary control whatsoever. When questioned as to how big a problem their incontinence was, 38% said it was no problem, 34% said it was a small problem, and 9% said it was a moderate to big problem. This report is consistent with other large studies on urinary incontinence following radical prostatectomy. Kao et al [51] recently studied 1069 men who underwent radical prostatectomy in the United States military health care system and found that 66% reported some degree of incontinence following surgery. In addition, 21% of patients experienced urethral strictures or bladder neck contractures that required dilatation or surgery. They specifically asked patients to rate their overall quality of
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life and found that 59% felt they had the same or better quality of life following treatment, and 37% felt that their quality of life was worse than before. Patients who reported incontinence were significantly less likely to report better posttreatment quality of life than those who were continent following treatment (odds ratio [OR] ¼ 0.41; 95% confidence interval [CI], 0.30–0.55). Like sexual dysfunction following surgery, the relationship between urinary function and bother is highly individualized: not all patients who experience urinary leakage are bothered by it. In a study of 132 men who underwent radical prostatectomy, 57% reported leakage with coughing, and 52% used pad protection, but only 19% reported that their urinary problems impacted their quality of life ‘‘quite a bit’’ or ‘‘very much’’ [36]. In another study of 1072 Medicare patients who underwent radical prostatectomy, 79% of the 230 men who reported dripping but no pad use said this was a very small or just a small problem, and 13% said it was a moderate or big problem. Of the 222 men who reported wearing pads or using penile clamps, 44% said it was only a very small or small problem, whereas 53% said it was a moderate or big problem [52]. These studies indicate that although there is some correlation between urinary leakage and bother, the relationship is far from direct, demonstrating again that the physical burden of urinary symptoms following surgery is highly individualized. Although the incidence of urinary stress incontinence is considerably less following external beam radiotherapy, this treatment can cause significant irritative voiding dysfunction that can be a burden for patients and can affect quality of life. Fransson and Widmark [53] compared HRQOL in 120 men who underwent external beam radiotherapy with 125 age-matched controls at 4 and 8 years after external beam radiotherapy. At 8 years after treatment, 54% of patients and 31% of controls reported urinary problems. Urinary function remained stable between years 4 and 8 after therapy. In another study of 129 patients treated with external beam radiotherapy [54], 15% reported urinary dysfunction to the extent that they had to modify their activities of daily living, and 2% felt virtually housebound by their irritative voiding symptoms. Clearly, the irritative voiding symptoms that can occur after radiotherapy can be as great a physical burden as stress incontinence. The incidence of urinary leakage after radiotherapy is less than that after surgery. Patients undergoing radiotherapy may still experience some
urinary leakage, although this leakage may not be caused by stress incontinence. In a populationbased study of 621 men who underwent external beam radiotherapy for localized prostate cancer, 7% wore pads to protect against wetness and leakage. In another population-based study of 2year quality-of-life outcomes in 421 men who underwent radiotherapy, 33% experienced some incontinence, and 44% experienced some urinary frequency. One fourth said that their incontinence was a small problem, and only 3% said it was a big problem. These studies indicate that incontinence can occur after external beam radiotherapy, although it is less of a problem than after surgery. Like men who undergo external beam radiotherapy for localized disease, patients receiving interstitial brachytherapy can experience urinary dysfunction. In a study of 51 men who underwent radioactive seed implantation at a single institution, 30% complained of persistent urinary symptoms 6 months following therapy. Forty percent of men complained of urinary frequency, and 17% complained of dysuria. In 3% of patients, urge incontinence, defined as difficulty in controlling urination, was reported. Ninety-three percent of patients required -blocker therapy for their urinary symptoms; of these patients, 75% reported improvement. Despite the high incidence of urinary problems, only 10% of patients reported decreased functional status [55] In another study, Lee et al [56] studied 46 men who received interstitial brachytherapy using a validated general HRQOL instrument, the FACT-P, and the International Prostate Symptom Score (IPSS). Three months after treatment, general quality of life had returned to baseline, but IPSS scores remained significantly higher than baseline (8.1 versus 15.3, P=0.0001), indicating that these patients had marked urinary symptoms. In another study of 70 men who received brachytherapy at a single institution, the probability of patients achieving urinary continence was approximately 40%, 50%, and 55% at 3, 6, and 9 months after therapy, respectively. Clearly, patients who undergo permanent radioactive seed implantation for prostate cancer experience significant urinary dysfunction after treatment. These symptoms can place a considerable burden on the patient and hence affect quality of life. Bowel function Although bowel dysfunction is fairly uncommon after prostatectomy, the unique mechanism of action of radiotherapy, either external beam or interstitial brachytherapy, can lead to significant
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bowel dysfunction in these patients. Widmark et al [57] reported that 59% of patients undergoing external beam radiotherapy report gastrointestinal problems, compared with 14% of agematched controls. Patients classified 90% of these problems as minor, however. This finding may explain why, despite a significant worsening of bowel function, most patients do not report any effect on HRQOL when compared with agematched controls [7]. In another study of 192 men who underwent external beam radiotherapy for localized disease, 25% reported moderate and 11% reported severe bowel changes, including fecal soiling (5% of total population) and bowel frequency (4%) [58]. Other series [54] have reported higher rates of fecal soiling and bowel frequency (10% and 7%, respectively). The effect of interstitial brachytherapy on bowel function has also been assessed. In one study of 51 brachytherapy patients [55], only 3% reported rectal bleeding, and no patients reported rectal discomfort or rectal ulceration. In contrast, Talcott et al [48] reported a 14% incidence in rectal urgency and a 6% incidence of rectal bleeding. Krupski et al [47] reported that the probability of experiencing problematic diarrhea following brachytherapy is approximately 20%, 15%, and 12% at 3, 6, and 9 months after therapy, respectively. Although few studies have examined the direct relationship between bowel dysfunction and overall quality of life following brachytherapy, there is no doubt that in some patients bowel symptoms, such as rectal urgency or diarrhea, do place a significant burden on those affected. Summary The physical burden of prostate cancer is considerable and affects quality of life in men with both localized and metastatic disease. This physical impact results as much from treatment for prostate cancer as from the disease itself. In advanced disease, although patients can experience considerable pain and discomfort from bony lesions, they also can experience bothersome fatigue and sleep disturbances from institution of hormone ablation therapy. In localized disease, although patients can have lower urinary tract symptoms from untreated prostate cancer, all aggressive treatments can result in urinary, sexual, and bowel dysfunction that can bother the patient and affect quality of life. Patients and providers must be vigilantly aware of the physical burden of prostate cancer when initiating treatment for this disease and during
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follow up after treatment. By being cognizant of the physical impact of prostate cancer on quality of life, providers can address patients’ problems early in their course of treatment and maximize patients’ HRQOL and overall satisfaction with care.
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[28] Chodak G, Sharifi R, Kasimis B, et al. Single-agent therapy with bicalutamide: a comparison with medical or surgical castration in the treatment of advanced prostate carcinoma. Urology 1995;46: 849–55. [29] Bouchot O, Lenormand L, Karam G, et al. Intermittent androgen suppression in the treatment of metastatic prostate cancer. Eur Urol 2000;38: 543–9. [30] Osoba D, Tannock IF, Ernst DS, et al. Healthrelated quality of life in men with metastatic prostate cancer treated with prednisone alone or mitoxantrone and prednisone. J Clin Oncol 1999; 17:1654–63. [31] Litwin MS, Lubeck DP, Stoddard ML, et al. Quality of life before death for men with prostate cancer: results from the CaPSURE database. J Urol 2001;165:871–5. [32] Turner SL, Gruenewald S, Spry N, et al. Less pain does equal better quality of life following strontium89 therapy for metastatic prostate cancer. Br J Cancer 2001;84:297–302. [33] Holmboe ES, Concato J. Treatment decisions for localized prostate cancer: asking men what’s important. J Gen Intern Med 2000;15:694–701. [34] Jonler M, Nielsen OS, Wolf H. Urinary symptoms, potency, and quality of life in patients with localized prostate cancer followed up with deferred treatment. Urology 1998;52:1055–62. [35] Lim AJ, Brandon AH, Fiedler J, et al. Quality of life: radical prostatectomy versus radiation therapy for prostate cancer. J Urol 1995;154:1420–5. [36] Shrader-Bogen CL, Kjellberg JL, McPherson CP, et al. Quality of life and treatment outcomes: prostate carcinoma patients’ perspectives after prostatectomy or radiation therapy. Cancer 1997;79:1977–86. [37] Sanchez-Ortiz RF, Broderick GA, Rovner ES, et al. Erectile function and quality of life after interstitial radiation therapy for prostate cancer. Int J Impot Res 2000;12(Suppl 3):S18–24. [38] Stanford JL, Feng Z, Hamilton AS, et al. Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study. JAMA 2000;283:354–60. [39] Talcott JA, Rieker P, Clark JA, et al. Patientreported symptoms after primary therapy for early prostate cancer: results of a prospective cohort study. J Clin Oncol 1998;16:275–83. [40] Litwin MS, Flanders SC, Pasta DJ, et al. Sexual function and bother after radical prostatectomy or radiation for prostate cancer: multivariate qualityof-life analysis from CaPSURE. Cancer of the Prostate Strategic Urologic Research Endeavor. Urology 1999;54:503–8. [41] Mantz CA, Song P, Farhangi E, et al. Potency probability following conformal megavoltage radiotherapy using conventional doses for localized prostate cancer. Int J Radiat Oncol Biol Phys 1997; 37:551–7.
D.F. Penson, M.S. Litwin / Urol Clin N Am 30 (2003) 305–313 [42] Hamilton AS, Stanford JL, Gilliland FD, et al. Health outcomes after external-beam radiation therapy for clinically localized prostate cancer: results from the Prostate Cancer Outcomes Study. J Clin Oncol 2001;19:2517–26. [43] Fowler Jr FJ, Barry MJ, Lu-Yao G, et al. Outcomes of external-beam radiation therapy for prostate cancer: a study of Medicare beneficiaries in three surveillance, epidemiology, and end results areas. J Clin Oncol 1996;14:2258–65. [44] Helgason AR, Fredrikson M, Adolfsson J, et al. Decreased sexual capacity after external radiation therapy for prostate cancer impairs quality of life. Int J Radiat Oncol Biol Phys 1995;32:33–9. [45] Brandeis J, Litwin M, Burnison C, et al. Quality of life outcomes after brachytherapy for early stage prostate cancer. J Urol 2000;163:851–7. [46] Joly F, Brune D, Couette JE, et al. Health-related quality of life and sequelae in patients treated with brachytherapy and external beam irradiation for localized prostate cancer. Ann Oncol 1998;9:751–7. [47] Krupski T, Petroni G, Bissonette E, et al. Qualityof-life comparison of radical prostatectomy and interstitial brachytherapy in the treatment of clinical localized prostate cancer. Urology 2000;55:736–42. [48] Talcott JA, Clark JA, Stark PC, et al. Long-term treatment related complications of brachytherapy for early prostate cancer: a survey of patients previously treated. J Urol 2001;166:494–9. [49] Merrick GS, Butler WM, Lief JH, et al. Temporal resolution of urinary morbidity following prostate brachytherapy. Int J Radiat Oncol Biol Phys 2000; 47:121–8. [50] Potosky AL, Legler J, Albertsen PC, et al. Health outcomes after prostatectomy or radiotherapy for
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The physical burden of prostate cancer David F. Penson, MD, MPHa,b,*, Mark S. Litwin, MD, MPHc a
VA Puget Sound Health Care System, Section of Urology, 112-UR 1660 S. Columbian Way, Seattle, WA 98108, USA b University of Washington School of Medicine, Box 356510 Seattle, WA 98195, USA c Department of Urology, UCLA School of Medicine, 66-124 CHS Box 951738, Los Angeles, CA, 90095-1738, USA
Prostate cancer remains the most frequently diagnosed solid tumor and the second leading cause of cancer death among American men. In 2001 alone, the American Cancer Society projected over 198,000 new diagnoses and 31,500 deaths from prostate cancer [1]. The sheer volume of prostate cancer cases represents a tremendous burden of disease that will probably increase in the future, primarily because patients are being diagnosed at a younger age and are living longer with their disease. Historically, prostate cancer has been considered a disease of elderly men. In the past decade, however, there has been a steady decrease in the average age at diagnosis [2] resulting at least in part from the introduction of serum prostate-specific antigen (PSA) testing. In fact, the largest increase in prostate cancer incidence during the PSA era, which began in the early 1990s, has occurred in men under age 65 years [2]. Recent data from the Seattle-Puget Sound Surveillance, Epidemiology and End Results (SEER) cancer registry for the period from 1995 to 1999 indicate that 33% of all incident prostate cancer cases are now diagnosed in men under age 65 years. The shift toward earlier age at diagnosis means that prostate cancer survivors will have longer life expectancies after diagnosis, regardless of treatment, and will therefore have more time to experience the physical, psychologic, and economic burdens of this highly prevalent malignancy.
* Corresponding author. VAPSHCS Section of Urology, 112-UR 1660 S. Columbian Way, Seattle, WA 98108. E-mail address: [email protected] (D.F. Penson).
In prostate cancer, the physical burden in particular can be onerous for the patient. Although there are many obvious examples of this burden, such as pain from metastatic bony lesions or discomfort caused by lower urinary tract symptoms from outlet obstruction, there are less apparent long-term effects of therapy that can cause significant physical problems for patients as well. All these physical effects of prostate cancer can profoundly affect quality of life. The shift toward earlier age at diagnosis means that prostate cancer survivors will have longer life expectancies after diagnosis, regardless of treatment, and will therefore have more time to experience the physical, psychologic, and economic burdens of this highly prevalent malignancy. This article provides a comprehensive description of the physical burden of both metastatic and localized prostate cancer and the associated treatments. Information in this report will be helpful for describing to patients the long-term effects of prostate cancer and its therapy and will aid in clinical decision-making while helping patients set reasonable expectations.
Assessing the physical burden of prostate cancer The physical impact of prostate cancer can profoundly affect quality of life. Therefore, one method of assessing the physical burden of this condition is to study health-related quality of life (HRQOL) in men with prostate cancer. Healthrelated quality of life involves patients’ perceptions of their own health and ability to function in life [3]. The concept of HRQOL includes not only functional status and symptoms of a given disease or treatment but also the degree of problems or
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difficulty that patients experience from their condition [4]. Health-related quality of life is a patient-centered variable, measured using questionnaires (also known as instruments) that are administered directly to patients in an objective manner. The principles of psychometric test theory are used to design instruments that reproducibly and accurately quantify HRQOL [5]. Healthrelated quality-of-life instruments typically contain questions, or items, that are organized into scales. Each scale measures a different aspect, or domain, of HRQOL. Typically, the items in a scale are combined to generate a numerical summary score for a particular domain; this score can then be used in statistical analyses. A number of established and validated HRQOL instruments have been specifically developed for men with prostate cancer. These instruments include the University of California, Los Angeles Prostate Cancer Index (UCLA PCI) [6,7], the Expanded Prostate Cancer Index Composite (EPIC) [8], the Functional Assessment of Cancer Therapy-Prostate (FACT-P) [9,10], and the Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) [11,12]. For more detail on the methodology of HRQOL measurement and the available instruments for assessing quality of life in prostate cancer, the reader is referred to the authors’ previous publication on this topic [13].
The physical burden of metastatic prostate cancer Given the predilection of prostate cancer to metastasize to bone as it advances, it is not surprising that patients with metastatic prostate cancer suffer a significant physical burden of disease that affects quality of life. Investigators have shown that as prostate cancer progresses, HRQOL worsens accordingly. For example, one study found that patients with hormone-resistant prostate cancer have worse outcomes than men with hormone-sensitive disease in the following HRQOL domains: role functioning (mean score= 63 versus 88); physical functioning (60 versus 85) and global quality of life (49 versus 74) [14]. Similarly, Kim et al [15] noted that among patients treated for metastases, those with progressive disease seemed to have worse quality of life than those with stable disease, particularly for pain, fatigue, sleep, and physical and role functioning. Although these studies demonstrate that the physical burden of metastatic disease and its impact on quality of life worsen as the disease progresses, other researchers have shown that the negative
effect of advancing disease on HRQOL can be reversed with appropriate treatment. For example, Albertsen et al [16] studied metastatic prostate cancer patients in remission treated with luteinizing hormone-releasing hormone (LHRH) agonists and flutamide and found that their general HRQOL was indistinguishable from an age-matched control population of men without prostate cancer. Taken as a whole, these studies indicate that advanced prostate cancer has a significant effect on the physical domains of HRQOL and that these effects can be reversed with administration of hormone ablation therapy in appropriate cases. Although hormone ablation therapy can improve HRQOL in men with symptomatic advanced prostate cancer, its role in asymptomatic patients with advanced disease is less clear. A number of studies now provide preliminary evidence that early hormonal therapy may prolong survival in men with asymptomatic advanced disease [17–19]. There is still considerable debate as to the optimal time to initiate therapy in these patients [20], because hormone ablation has a number of physical side effects that may affect HRQOL. Herr and O’Sullivan [21] compared patients receiving hormonal therapy versus observation for asymptomatic advanced disease. Although there may have been significant selection bias because of the observational nature of the study, patients who elected to defer treatment had better HRQOL than those who opted for early intervention. In particular, men who received early therapy experienced significantly more fatigue and hot flashes that affected quality of life than those who delayed treatment. This report confirmed findings from a similar, earlier study from the same group [22]. These data indicate that, when discussing immediate versus deferred hormone ablation therapy for asymptomatic advanced prostate cancer, patients and providers must carefully weigh the possible survival benefit against the physical side effects of early treatment and their impact on HRQOL. Once patients elect to receive treatment for metastatic prostate cancer, there is little difference in HRQOL outcomes between men undergoing medical versus surgical castration. Litwin et al [23] identified no differences in any of the general or disease-specific domains of the RAND 36 Item Health Survey (SF-36) or the UCLA Prostate Cancer Index when comparing men who underwent orchiectomy and those receiving combined androgen blockade. In a similar study, Cassileth et al [24] questioned 159 men who underwent
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either medical or surgical castration for advanced disease and found no difference in satisfaction with treatment choice 3 months after initiation of therapy. Although the method of castration does not seem to have a significant impact on HRQOL, the presence or absence of additional androgen-blocker therapy does influence HRQOL. In a clinical trial of 739 men with stage M1 prostate cancer, patients randomly assigned to treatment with orchiectomy plus flutamide reported significantly more diarrhea than those who were randomly assigned to orchiectomy plus placebo [25]. The negative impact on HRQOL of the gastrointestinal side effects of androgen-receptor blockade may be less in patients receiving bicalutamide [26]. Because hormone ablation therapy has a significant effect on HRQOL, there has been an increasing interest in the potential role of bicalutamide monotherapy in the initial treatment of advanced prostate cancer. Studies have shown that patients who receive antiandrogen monotherapy have fewer sexual side effects than those who receive hormone ablation therapy. Boccardo et al [27] randomly assigned 220 men with advanced disease to receive either bicalutamide alone or combined androgen blockade. They found no difference in progression-free or overall survival (median follow up, 38 months), and the bicalutamide monotherapy group was noted to have better libido and erectile function (P ¼ 0.01 and 0.002, respectively) than the group treated with combined androgen blockade. In a similar study, Chodak et al [28] randomly assigned 486 men to receive either antiandrogen monotherapy or castration. As in the earlier study, these investigators found that the monotherapy group had better sexual interest and function than the castration group. These studies demonstrate that antiandrogen monotherapy may be a reasonable alternative to traditional hormone ablation regimens. Unfortunately, these studies do not provide long enough follow up to determine how the therapies compare in terms of survival. Intermittent hormone ablation therapy has also been popularized as a possible alternative in the treatment of advanced, hormonally sensitive prostate cancer, because it may result in better quality of life with minimal, if any, difference in overall survival. Bouchot et al [29] prospectively assessed HRQOL outcomes in 43 men with symptomatic, advanced prostate cancer treated with an intermittent hormone ablation regimen. They noted that, after initiation of hormonal ablation therapy, these patients had significant improvement in bony pain and urologic symptoms. When the patients went
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into an off-treatment period, urologic symptoms often recurred, whereas bony pain did not. Although these studies are promising, additional research is needed to identify clearly novel ways to minimize the physical impact of hormonally naive, metastatic prostate cancer and its treatments. Men with hormone-resistant prostate cancer have worse quality of life than those with hormone-sensitive disease. A number of studies have documented that various chemotherapeutic agents improve HRQOL in men with hormone-resistant disease. For example, Osoba et al [30] assessed HRQOL in 161 men randomly assigned to receive prednisone alone versus prednisone and mitoxantrone over a 26-week follow-up period. At 6 weeks, patients taking prednisone alone showed no improvement in HRQOL scores, whereas those taking mitoxantrone plus prednisone showed significant improvements in global quality of life (P=0.009) and in four functional domains (P < 0.01). In the crossover arm of the study, the addition of mitoxantrone to prednisone after failure of prednisone alone was associated with improvements in pain, pain impact, pain relief, insomnia, and global quality of life (P < 0.003) After 18 weeks of therapy, those receiving mitoxantrone plus prednisone continued to improve in 11 of the 14 function and symptom scales used to measure HRQOL. This study and others [31,32] demonstrate that palliative chemotherapy can lessen the physical burden of prostate cancer in men with advanced, hormone-resistant disease. Although these treatments may not prolong life expectancy, a documented quality-of-life advantage for a given treatment will result in benefit to the patient and should be strongly considered when choosing therapies.
The physical burden of localized disease Untreated disease When patients and providers think of the physical burden of localized prostate cancer, they tend to focus on the well-known side effects of aggressive treatment–impotence and incontinence [33]. Localized prostate cancer in and of itself can cause significant lower urinary tract symptoms (LUTS) and other physical problems if left untreated. Unfortunately, few studies have examined the quality-of-life impact of localized disease managed expectantly. Jonler et al [34] assessed HRQOL in 52 consecutive patients who elected watchful
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waiting and deferred treatment for localized prostate cancer. Over a median follow up of 3.3 years, 31% required transurethral resection of the prostate gland for LUTS or acute urinary retention. Patients in the study reported a high incidence of dripping at least some urine daily (37%), pad use (21%), problematic urinary incontinence (21%), and urethral strictures (21%). Thirty-five percent reported that they were bothered by their prostate cancer or by additional treatment they had received. This study indicates that localized prostate cancer has an independent physical impact on quality of life that often creates problems for patients. This is important information that providers and patients should consider if they are considering conservative management of localized prostate cancer. The physical impact of aggressive therapies on quality of life Currently, the most commonly used treatment modalities for localized prostate cancer include radical prostatectomy, external beam radiotherapy, and interstitial brachytherapy. All these treatments have side effects that can profoundly affect patients’ sexual, urinary, and bowel function. Numerous studies have looked at larger issues such as long-term physical function and bodily pain and have found no differences among these treatments. Litwin et al [7] compared general HRQOL in 214 men undergoing prostatectomy, radiotherapy, or conservative management and found no significant differences between the groups. Lim et al [35] and Shrader-Bogen et al [36] performed similar studies and noted no differences in general HRQOL among treatments. More recently, Sanchez-Ortiz et al [37] studied 171 patients who underwent either palladium or iodine interstitial brachytherapy and found no differences in general HRQOL outcomes between the two radiation sources. Although the aggressive therapies lead to similar outcomes in terms of general physical function, they differ significantly in long-term sexual, urinary, and bowel function following treatment. Sexual function Of the three aggressive therapies commonly used for treatment of localized prostate cancer, radical prostatectomy (RP) is commonly thought to have the highest incidence of post-treatment sexual dysfunction. Stanford et al [38] reported longitudinal quality of life outcomes of 1291 men who underwent RP for localized disease from the
Prostate Cancer Outcomes Study (PCOS), a population-based cohort of men diagnosed with prostate cancer from 6 geographic regions within the SEER program of the National Cancer Institute. At baseline, 73% of men reported erections firm enough for sexual intercourse, and 45% of men reported no difficulty in maintaining an erection. At 2 years following surgery, 19% of men reported erections firm enough for intercourse, and 7% of men reported no difficulties maintaining an erection. When asked how big a problem their sexual function was at 2 years following surgery, 14% said it was no problem, 23% said it was a small problem, and 42% said it was a moderate to big problem. This study demonstrates that patients have a significant amount of sexual dysfunction following surgery and that this dysfunction affects quality of life, because a considerable number of patients experience bother from their symptoms. It is important to note, however, that the degree of dysfunction and bother do not correlate as well one might expect, indicating that the effect of erectile dysfunction on patients’ quality of life is variable and highly idiosyncratic. The use of the nerve-sparing radical prostatectomy technique is purported to improve potency following surgery for localized prostate cancer. Studies examining quality-of-life outcomes following nerve-sparing prostatectomy have been mixed, however. Talcott et al [39] compared HRQOL outcomes in 28 men who underwent non–nerve-sparing radical prostatectomy with 66 men who underwent either unilateral or bilateral nerve-sparing surgery at a single institution. They found that men who underwent any type of nervesparing procedure had worse sexual function than had been previously reported and found no statistically significant differences in sexual functioning between the groups receiving nerve-sparing and non–nerve-sparing procedures. Using a multicenter observational disease registry, Litwin et al [40] studied 218 men who underwent nervesparing radical prostatectomy and 124 men who underwent the non–nerve-sparing technique. They found that the patients who underwent nerve-sparing surgery had significantly better sexual function than those who had non–nervesparing surgery at 6, 12, and 18 months following treatment, although the overall level of sexual function was low for both groups. Given the multi-institutional nature of this study, these results probably better represent the effectiveness of nerve-sparing surgery in the general population.
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Significant sexual dysfunction can occur after both external beam radiotherapy and interstitial brachytherapy as well. In a study of 287 men who underwent conformal external beam radiation therapy for localized prostate cancer, Mantz et al [41] noted actuarial potency rates of 96%, 75%, 59%, and 53% at 1, 20, 40, and 60 months after therapy, respectively. Other studies have shown that, similar to the situation following surgery, the effect of erectile dysfunction on quality of life is highly individualized. Hamilton et al [42] studied the impact of external beam radiotherapy on 497 men from PCOS, a population-based cohort of patients with localized prostate cancer. They found that 43% of men who were potent before diagnosis were impotent 2 years after radiotherapy, but more than two thirds of these men were satisfied with their treatment and would choose the same option again, indicating that their sexual dysfunction was not a great problem for them. Fowler et al [43] studied 432 Medicare patients who underwent external beam radiotherapy and found that only 37% reported that their sexual function was a ‘‘medium or big problem,’’ although the amount of erectile dysfunction was no doubt higher than that. Helgason et al [44] studied 53 men who had undergone external beam radiotherapy for localized prostate cancer and noted that 77% reported diminished sexual desire, 34% reported erections insufficient for intercourse, and 77% reported some loss of stiffness. More importantly, 50% of men reported that their overall quality of life had decreased much or very much as a direct result of decreased erectile function. Clearly, sexual dysfunction is a relatively common occurrence after external beam radiotherapy, although, as after surgery, it may or may not be a significant problem for the patient. Finally, erectile dysfunction can also occur after interstitial brachytherapy. Brandeis et al [45] found that, at 3 to 17 months following treatment, sexual function in the brachytherapy group was significantly worse than in age-matched controls. Other studies have also noted that sexual function following brachytherapy is worse than that of agematched controls [46]. To quantify the degree of sexual dysfunction following this treatment, Krupski et al [47] studied HRQOL in 70 patients who received isolated brachytherapy for localized disease and found that at 3, 6, and 9 months following treatment, patients had an approximately 25%, 40%, and 55% probability of being able to achieve penile erection adequate for sexual intercourse. In another study, Talcott et al [48]
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reported a 44% incidence of complete impotence in men who had undergone brachytherapy with varying degrees of follow up following treatment. Further research with longer-term follow up is needed to understand better the impact of erectile dysfunction on quality of life in brachytherapy patients. These studies demonstrate that, like other aggressive treatment for localized prostate cancer, brachytherapy commonly results in erectile dysfunction that can affect HRQOL and represents a significant physical burden for patients with this disease. Urinary function Urinary dysfunction is also common after aggressive therapy for localized prostate cancer, although the type of dysfunction depends on the treatment received. Patients who undergo radical surgery are more likely to report stress urinary incontinence, whereas men undergoing either external beam radiotherapy or interstitial brachytherapy often experience significant irritative voiding symptoms [42,49,50]. Although the type of urinary dysfunction differs among treatments, the impact on HRQOL is considerable with both surgery and radiotherapy and represents a significant burden of disease for patients. Radical prostatectomy is associated with a significant incidence of postoperative side effects, including stress urinary incontinence and bladder neck contractures that can cause obstructive voiding symptoms and urinary retention. A recent publication from the Prostate Cancer Outcomes Study, a population-based cohort of men with prostate cancer, reported on longitudinal qualityof-life outcomes in 1291 men who underwent radical prostatectomy [38]. Two years after surgery, 32% of the men reported total urinary control, 40% reported occasional leakage, 7% reported frequent leakage, and 2% had no urinary control whatsoever. When questioned as to how big a problem their incontinence was, 38% said it was no problem, 34% said it was a small problem, and 9% said it was a moderate to big problem. This report is consistent with other large studies on urinary incontinence following radical prostatectomy. Kao et al [51] recently studied 1069 men who underwent radical prostatectomy in the United States military health care system and found that 66% reported some degree of incontinence following surgery. In addition, 21% of patients experienced urethral strictures or bladder neck contractures that required dilatation or surgery. They specifically asked patients to rate their overall quality of
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life and found that 59% felt they had the same or better quality of life following treatment, and 37% felt that their quality of life was worse than before. Patients who reported incontinence were significantly less likely to report better posttreatment quality of life than those who were continent following treatment (odds ratio [OR] ¼ 0.41; 95% confidence interval [CI], 0.30–0.55). Like sexual dysfunction following surgery, the relationship between urinary function and bother is highly individualized: not all patients who experience urinary leakage are bothered by it. In a study of 132 men who underwent radical prostatectomy, 57% reported leakage with coughing, and 52% used pad protection, but only 19% reported that their urinary problems impacted their quality of life ‘‘quite a bit’’ or ‘‘very much’’ [36]. In another study of 1072 Medicare patients who underwent radical prostatectomy, 79% of the 230 men who reported dripping but no pad use said this was a very small or just a small problem, and 13% said it was a moderate or big problem. Of the 222 men who reported wearing pads or using penile clamps, 44% said it was only a very small or small problem, whereas 53% said it was a moderate or big problem [52]. These studies indicate that although there is some correlation between urinary leakage and bother, the relationship is far from direct, demonstrating again that the physical burden of urinary symptoms following surgery is highly individualized. Although the incidence of urinary stress incontinence is considerably less following external beam radiotherapy, this treatment can cause significant irritative voiding dysfunction that can be a burden for patients and can affect quality of life. Fransson and Widmark [53] compared HRQOL in 120 men who underwent external beam radiotherapy with 125 age-matched controls at 4 and 8 years after external beam radiotherapy. At 8 years after treatment, 54% of patients and 31% of controls reported urinary problems. Urinary function remained stable between years 4 and 8 after therapy. In another study of 129 patients treated with external beam radiotherapy [54], 15% reported urinary dysfunction to the extent that they had to modify their activities of daily living, and 2% felt virtually housebound by their irritative voiding symptoms. Clearly, the irritative voiding symptoms that can occur after radiotherapy can be as great a physical burden as stress incontinence. The incidence of urinary leakage after radiotherapy is less than that after surgery. Patients undergoing radiotherapy may still experience some
urinary leakage, although this leakage may not be caused by stress incontinence. In a populationbased study of 621 men who underwent external beam radiotherapy for localized prostate cancer, 7% wore pads to protect against wetness and leakage. In another population-based study of 2year quality-of-life outcomes in 421 men who underwent radiotherapy, 33% experienced some incontinence, and 44% experienced some urinary frequency. One fourth said that their incontinence was a small problem, and only 3% said it was a big problem. These studies indicate that incontinence can occur after external beam radiotherapy, although it is less of a problem than after surgery. Like men who undergo external beam radiotherapy for localized disease, patients receiving interstitial brachytherapy can experience urinary dysfunction. In a study of 51 men who underwent radioactive seed implantation at a single institution, 30% complained of persistent urinary symptoms 6 months following therapy. Forty percent of men complained of urinary frequency, and 17% complained of dysuria. In 3% of patients, urge incontinence, defined as difficulty in controlling urination, was reported. Ninety-three percent of patients required -blocker therapy for their urinary symptoms; of these patients, 75% reported improvement. Despite the high incidence of urinary problems, only 10% of patients reported decreased functional status [55] In another study, Lee et al [56] studied 46 men who received interstitial brachytherapy using a validated general HRQOL instrument, the FACT-P, and the International Prostate Symptom Score (IPSS). Three months after treatment, general quality of life had returned to baseline, but IPSS scores remained significantly higher than baseline (8.1 versus 15.3, P=0.0001), indicating that these patients had marked urinary symptoms. In another study of 70 men who received brachytherapy at a single institution, the probability of patients achieving urinary continence was approximately 40%, 50%, and 55% at 3, 6, and 9 months after therapy, respectively. Clearly, patients who undergo permanent radioactive seed implantation for prostate cancer experience significant urinary dysfunction after treatment. These symptoms can place a considerable burden on the patient and hence affect quality of life. Bowel function Although bowel dysfunction is fairly uncommon after prostatectomy, the unique mechanism of action of radiotherapy, either external beam or interstitial brachytherapy, can lead to significant
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bowel dysfunction in these patients. Widmark et al [57] reported that 59% of patients undergoing external beam radiotherapy report gastrointestinal problems, compared with 14% of agematched controls. Patients classified 90% of these problems as minor, however. This finding may explain why, despite a significant worsening of bowel function, most patients do not report any effect on HRQOL when compared with agematched controls [7]. In another study of 192 men who underwent external beam radiotherapy for localized disease, 25% reported moderate and 11% reported severe bowel changes, including fecal soiling (5% of total population) and bowel frequency (4%) [58]. Other series [54] have reported higher rates of fecal soiling and bowel frequency (10% and 7%, respectively). The effect of interstitial brachytherapy on bowel function has also been assessed. In one study of 51 brachytherapy patients [55], only 3% reported rectal bleeding, and no patients reported rectal discomfort or rectal ulceration. In contrast, Talcott et al [48] reported a 14% incidence in rectal urgency and a 6% incidence of rectal bleeding. Krupski et al [47] reported that the probability of experiencing problematic diarrhea following brachytherapy is approximately 20%, 15%, and 12% at 3, 6, and 9 months after therapy, respectively. Although few studies have examined the direct relationship between bowel dysfunction and overall quality of life following brachytherapy, there is no doubt that in some patients bowel symptoms, such as rectal urgency or diarrhea, do place a significant burden on those affected. Summary The physical burden of prostate cancer is considerable and affects quality of life in men with both localized and metastatic disease. This physical impact results as much from treatment for prostate cancer as from the disease itself. In advanced disease, although patients can experience considerable pain and discomfort from bony lesions, they also can experience bothersome fatigue and sleep disturbances from institution of hormone ablation therapy. In localized disease, although patients can have lower urinary tract symptoms from untreated prostate cancer, all aggressive treatments can result in urinary, sexual, and bowel dysfunction that can bother the patient and affect quality of life. Patients and providers must be vigilantly aware of the physical burden of prostate cancer when initiating treatment for this disease and during
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follow up after treatment. By being cognizant of the physical impact of prostate cancer on quality of life, providers can address patients’ problems early in their course of treatment and maximize patients’ HRQOL and overall satisfaction with care.
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