Acute bowel morbidity after prostate brachytherapy with cesium-131

Article Outline

• Abstract
• Introduction
• Methods and materials
• Results
• Discussion
• Conclusion
• Appendix. 
• References
• Copyright

Abstract 

Purpose

The present study evaluates the severity and time to resolution of bowel symptoms in men undergoing prostate brachytherapy (PB) with cesium-131 (¹³¹Cs).

Methods and Materials

A longitudinal, prospective study of patients who had undergone PB with ¹³¹Cs at a single institution was performed. All patients were asked to complete the Expanded Prostate Cancer Index Composite preoperatively and at 2 weeks and 1, 3, and 6 months postoperatively. Outcomes were analyzed using descriptive statistics and Student’s t test.

Results

The first 142 patients to have undergone PB with ¹³¹Cs at our institution were included in the study. The mean Expanded Prostate Cancer Index Composite bowel summary score at baseline was 90.1±11.0 compared with 71.5±22.8 (p=0.000), 70.1±20.7, 87.1±13.8 (p=0.01), and 90.7±9.2 (p=0.70) at 2 weeks and 1, 3, and 6 months postoperatively, respectively.

Conclusions

In men undergoing PB as monotherapy with ¹³¹Cs, bowel symptoms returned to baseline by 3 months after the procedure. For patients undergoing PB with ¹³¹Cs as part of combination therapy, bowel symptoms return to their post–external beam radiotherapy, pre-PB baseline by 3 months after the procedure.

Keywords: Cesium-131, Quality of life, Brachytherapy, EPIC, Prostate cancer

Back to Article Outline

Introduction 

An estimated 192,280 cases of prostate cancer (CaP) will be diagnosed in 2009 with an estimated 27,360 deaths (1). Among the various available treatment options, prostate brachytherapy (PB) has been shown to be an effective treatment for clinically localized CaP (2). Several centers have published outcomes with long-term followup, demonstrating excellent cancer control, with prostate-specific antigen relapse–free survival equivalent to radical prostatectomy and external beam radiotherapy (EBRT) [3], [4], [5]. Given the lack of clear superiority in cancer control of the different treatment options and the slow growing nature of CaP, consideration of health-related quality of life (HRQOL) after treatment has become increasingly important (6).

Patients who choose PB are attracted to the minimally invasive nature of the procedure, the quick return to full activity, and the low risk of long-term urinary incontinence. Bothersome urinary and bowel symptoms, however, occur quite commonly after PB. These symptoms can persist for more than 12 months after the procedure and can significantly affect the quality of life [7], [8], [9], [10].

Recently, a new radioisotope, cesium-131 (¹³¹Cs) (IsoRay Medical Inc., Richland, Washington, DC), has been introduced for use in PB (11). A major proposed benefit of ¹³¹Cs is a shorter duration of the bothersome brachytherapy-related symptoms when compared with iodine-125 (¹²⁵I) and palladium-103 (¹⁰³Pd) [12], [13]. Our center has recently begun using ¹³¹Cs, and the present study reports the severity and duration of bowel morbidity in our initial experience.

Back to Article Outline

Methods and materials 

The present study is a longitudinal, prospective analysis of the first 142 patients who underwent PB with implantation of the ¹³¹Cs isotope at our institution and was approved by our Institutional Review Board. The isotope was implanted using real-time planning. Seeds were placed by afterloading with a Mick applicator (Mick Radio-Nuclear Instruments, Inc., Mount Vernon, NY). Prostate volume was measured preoperatively (by means of either CT or ultrasound) to estimate the activity required. At the time of the implant, the prostate volume was measured using a step section technique at 5-mm intervals from the base of the prostate to the apex.

Peripheral needles were placed first, approximately 8–10mm apart and just under the capsule of the prostate in the largest transverse image, and two to eight central needles (depending on prostate volume and geometry) were then placed to ensure adequate dosing of the central portion of the gland. Posterior needles were kept approximately 5mm from the posterior prostate capsule. After all the needles were placed, post-needle prostate volume was obtained by again contouring the prostate in transverse sections in 5-mm intervals from base to apex. Real-time intraoperative dosimetry (VariSeed 7.1; Varian Medical Systems, Palo Alto, CA) was used to determine the location of seed placement based on the post-needle prostate volume and geometry on ultrasound. Real-time planning indicates that the final plan was not created until all needles were placed and located on the planning software. A modified peripheral loading technique was used. Dosimetry targets were as follows: D₉₀>110%, V₁₀₀>90%, V₁₅₀<50%, V₂₀₀<15%, and R₁₀₀<1.5cc. For men undergoing combined radiotherapy, they underwent PB 4 weeks after their EBRT was complete.

Patients were generally discharged the day of the procedure. If patients were unable to void adequately, they were discharged with a foley catheter. Patients were instructed to follow up at 2 weeks and 1, 3, and 6 months after their procedure. Expanded Prostate Cancer Index Composite (EPIC) surveys were completed preoperatively and at each followup appointment; by collecting baseline HRQOL data, patients served as their own controls. For patients undergoing combined radiotherapy, preoperative EPIC surveys were completed after EBRT and before undergoing PB. The first 142 patients in our ¹³¹Cs experience were included in the study, as these patients were a minimum of 6 months out from their procedure.

The 50-item EPIC survey, which is based on modifications to the University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), has shown satisfactory survey characteristics in validation analyses; has test–retest reliability; and has internal consistency for urinary, bowel, sexual, and hormonal domains. The EPIC survey specifically addresses both urinary and bowel bother and function components (14) Each domain is scored from 0 to 100, with higher scores representing better HRQOL. Similar to other authors, our study used a mean difference of 10 points to define clinical significance, because this represented 1 standard deviation from the mean according to the authors of the original EPIC [15], [16]. The portion of the EPIC survey relating to bowel function appears in the Appendix.

Results were analyzed using descriptive statistics and Student’s t test using SAS 8.2 statistical software (SAS Institute, Cary, NC). All p-values are two sided, with p< 0.05 considered statistically significant.

Back to Article Outline

Results 

The patients’ demographic information appears in Table 1. The mean age at the time of treatment was 66.2±6.8 years, mean prostate-specific antigen was 6.6±6.6ng/mL, and median Gleason score was 7. There were no perioperative complications. The numbers of patients with low, intermediate, and high-risk prostate cancers, as defined by D’Amico et al., were 64 (45%), 62 (44%), and 16 (11%), respectively (18). Ninety-one patients (64%) had PB as monotherapy (115Gy), whereas 43 patients (30%) had combined radiotherapy, consisting of 5 weeks of EBRT (4500cGy in 25 fractions) followed by PB with ¹³¹Cs (85Gy). Within this cohort, 14 patients (10%) received trimodal therapy consisting of androgen-deprivation therapy (ADT), EBRT, and PB. Eight patients (6%) had PB and ADT.

Table 1. Patient characteristics

PSA=prostate-specific antigen.

aClinical stage is based on the American Joint Commission on Cancer Staging T stage (17).

bLow risk: T1c or T2a, PSA level⩽10, and Gleason score⩽6; intermediate risk: T2b, PSA level>10 and ⩽20, or Gleason score of 7; and high risk: T2c, PSA level>20, or Gleason score⩾8 (18).

A total of 568 EPIC surveys were completed. The numbers of preoperative, 2-week, and 1-, 3-, and 6-month surveys reviewed were 142 (100%), 124 (87.3%), 84 (59.1%), 128 (90.1%), and 90 (63.4%), respectively. If surveys were not complete, they were discarded and counted as no response.

Table 2 contains the pre- and posttreatment EPIC values for bowel summary scores as well as for the bowel function and bother subgroups for all patients. For the bowel summary scores and the function and bother subgroups, patients returned to their clinical baseline by 3 months and had scores that were not statistically different from baseline by 6 months. The bowel EPIC scores for the subgroup of patients who underwent combined radiotherapy with EBRT followed by PB appear in Table 3. In this group, using the patients’ post-EBRT and prebrachytherapy EPIC survey as their baseline before implantation, patients returned to both clinical and statistical baseline by 3 months. The 99 patients receiving PB as monotherapy are depicted in Table 4. Similar to the total cohort, these patients returned to clinical baseline by 3 months and had scores that were not statistically different from baseline by 6 months.

Table 2. Expanded Prostate Cancer Index Composite scores for bowel domains of all patients

SD=standard deviation.

aThe Student’s t test was used to test statistical significance. A p-value <0.05 was considered significant.

Table 3. Expanded Prostate Cancer Index Composite scores for bowel domains of patients post–external beam radiotherapy receiving brachytherapy

SD=standard deviation.

aThe Student’s t test was used to test statistical significance. A p-value <0.05 was considered significant.

Table 4. Expanded Prostate Cancer Index Composite scores for bowel domains of patients receiving prostate brachytherapy as monotherapy

SD=standard deviation.

aThe Student’s t test was used to test statistical significance. A p-value <0.05 was considered significant.

Patients who underwent PB as monotherapy were compared directly with patients who underwent PB as part of combination therapy with EBRT. The only significant differences between these two groups occurred in the bowel function subscale at 2 weeks and in both the bowel summary and bowel function subscales at 4 weeks. Men who underwent PB as monotherapy had lower scores in each of these occurrences (67.8 vs. 79.8 for bowel function at 2 weeks, 66.7 vs. 81.5 for bowel function at 4 weeks, and 66.9 vs. 79.4 for bowel summary at 4 weeks). Patients who received ADT were compared with patients who had not received ADT, and no statistically significant difference was found between the two groups at any time point.

The bowel portion of the EPIC survey contains 14 questions that address bowel symptoms, such as bowel urgency, frequency, abdominal pain, and bleeding, as well as the degree of bother from those symptoms. The bowel portion of the EPIC survey appears in the Appendix. The greatest change from baseline occurred in the questions dealing with rectal urgency, overall bother, and frequency. The smallest change from baseline occurred in the questions dealing with incontinence, consistency of bowel movements, and bloody stools. The only questions that did not return to statistical baseline by 3 months after the procedure were the questions dealing with bowel frequency and overall bother.

Back to Article Outline

Discussion 

This longitudinal, prospective study of the first 142 patients to undergo PB with the ¹³¹Cs radioisotope at a single institution describes the postoperative bowel morbidity in patients implanted with ¹³¹Cs. Using the EPIC survey as its instrument, the present study finds that bowel summary and subgroup scores were at their most severe levels 2–4 weeks after the procedure and generally returned to clinical baseline by 3 months and statistical baseline by 6 months after the procedure.

Over the past several years, ¹²⁵I and ¹⁰³Pd have been the most common isotopes used for PB. ¹³¹Cs is a newer radioisotope that we began using at our institution in 2006. The appeal of ¹³¹Cs is that its half-life of 9.7 days is shorter than the half-life of both ¹²⁵I (∼60 days) and ¹⁰³Pd (∼17 days), with an energy level similar to that of ¹²⁵I (∼29keV), which potentially leads to a shorter duration of bothersome brachytherapy-related side effects [12], [13], [19]. Currently, no long-term data exist for ¹³¹Cs. To our knowledge, this is the first study to examine the acute bowel symptoms after PB with the ¹³¹Cs radioisotope.

In our study, patients’ pre- and postoperative bowel symptoms were obtained using the validated EPIC survey, which allowed us to collect data prospectively and objectively in a longitudinal fashion. The issue of how statistical significance translates into clinical significance is important to consider. Several studies have described no direct relationship between p-values and clinical significance (20). Unlike the International Prostate Symptom Score (IPSS) questionnaire, the clinical meaningfulness of changes in the EPIC survey has not been studied. Frank et al. declared a 10-point differential in the EPIC survey as clinically significant, because 10 points represent 1 standard deviation from the mean according to the original authors of EPIC (15). The EPIC survey was developed at the University of Michigan, which created the instrument by expanding on the UCLA-PCI. Because the EPIC survey is based on the UCLA-PCI, it is important to note that differences of 10 points on the UCLA scales are also considered clinically meaningful (16). The present study, therefore, also uses a 10-point difference in the EPIC score to denote a clinically meaningful change.

The difficulty in correlating statistical significance with clinical significance in patient-completed surveys is certainly illustrated in the present study. For example, although the difference in bowel summary scores for all patients is still statistically significant at 3 months, the preoperative mean score was 90.1, and the mean score at 3 months was 87.1. It seems hard to argue that significant clinical differences existed 3 months post-procedure when the difference between mean scores was only 3 points out of a 100-point scale with similar standard deviations. Similar small differences in mean scores at 3 months are seen for bowel function and bowel bother domains in all patients as well as the subgroups of men undergoing PB as monotherapy and men undergoing combined radiotherapy.

Rectal morbidity is a well-known side effect of PB. Severe rectal complications after PB are rare, but 4–12% of the patients develop self-limited proctitis and <1% progress to ulceration and/or fistula formation [20], [21]. Merrick et al. followed a cohort of 219 patients at 28 and 66 months and 9 years after PB treatment with either ¹²⁵I or ¹⁰³Pd [22], [23], [24]. These patients did not report any severe changes in bowel function, and the percentages of patients who noted worsening bowel function after PB were 19%, 12%, and 10%, at 28 and 66 months and 9 years, respectively. These findings were consistent with those of Miller et al., who reported that bowel morbidity, although persistent among a subset of patients 4–8 years after treatment with PB, was less problematic than that in the first 2 years of followup (25). Hence, acute rectal morbidity is important to note, not only for short-term quality of life but also for long-term function.

Few studies have analyzed acute bowel morbidity with the EPIC survey. Sanda et al., in their review of quality of life among patients undergoing either radical prostatectomy, PB, or EBRT, had patients complete the EPIC survey preoperatively and at 2, 6, 12, and 24 months postoperatively (26). The results were represented in figures, making direct comparison of values with the present study difficult, but most patients reported a decrease in quality of life related to bowel function at 1 year. Nine percent of patients reported distress related to rectal urgency, frequency, pain, fecal incontinence, or hematochezia at that time (26). Ash et al. (8) reported data on 673 patients who had undergone PB with ¹²⁵I between 1995 and 2004. Patients who had presented with prostate volumes >50mL underwent 3 months of neoadjuvant hormone therapy, which was discontinued within 1 month of implantation. Most patients completed an IPSS questionnaire, and a subgroup of 116 patients completed the EPIC survey preoperatively and at 4–6 weeks, every 4 months for the first year and every 6 months in the second year (8). The mean bowel summary score was 92.2 preoperatively, 84.7 at 6 weeks, and had returned to that at baseline at 1 year (8). Ash et al. did not show a clinically significant difference in bowel function at 6 weeks, and bowel patterns returned to statistical baseline at 1 year (8).

Ferrer et al. evaluated 614 patients, of whom 275 underwent PB as monotherapy with ¹²⁵I for treatment of localized prostate cancer (27). Data from EPIC surveys were evaluated from preoperative assessment as well as at 3, 6, 12, and 24 months postoperatively (27). Pretreatment EPIC score for the bowel summary domain was 97.0±6.2. Compared with baseline scores, bowel summary scores were 95.3 (p=0.07), 95.2 (p=0.11), 96.8 (p=1.0), and 97.9 (p=0.26), at 3, 6, 12, and 24 months, respectively. No clinically or statistically significant difference was detected in the bowel summary score at any postoperative period, starting at 3 months (27).

In comparing the results of these studies with the present study, the preoperative bowel summary score in the present study was 90.1±11.0, which was lower than those of both Ash et al. (92.2) (8) and Ferrer et al. (97.0) (27). Bowel summary score in the present study reached a nadir at 4 weeks (70.1±20.7, p=0.000) and returned to statistical baseline by 6 months (90.7±9.2, p=0.70). The other bowel domains (function and bother) followed a similar pattern. Overall, the duration of the bowel morbidity among patients in the present study was similar to those reported by Ash et al. (8) and Ferrar et al. (27) and less than those in other studies that reported a return to statistical baseline a year or more after treatment [7], [8], [9], [10].

When comparing the bowel morbidity of patients who had EBRT before PB with those who had not received EBRT, patients curiously had a return to baseline sooner, reaching both clinical and statistical baseline by 3 months. This subgroup had a similar baseline bowel summary score as the overall cohort (89.9 vs. 90.6). The likely explanation for this finding is that the additive symptoms from PB were not as noticeable after having already experienced bowel symptoms from prior EBRT.

Many HRQOL studies report cross-sectional data and/or use age-matched controls [15], [22], [23], [24], [25], [28]. The strengths of this study are that it is a prospective, longitudinal study with multiple followup measurements, represents the first clinical data available for ¹³¹Cs PB in terms of short-term bowel morbidity, and contains a large number of patients. The results in the present study are based on short-term followup; long-term results are needed to determine if, in the small percentage of patients with prolonged rectal morbidity, symptoms continue to improve with time as they do in patients undergoing PB with ¹²⁵I and ¹⁰³Pd [24], [25].

The present study does have several limitations. The results are from a single institution, which raises the question of their generalizability. Although the longitudinal, prospective nature of this study is an improvement over a study that is cross-sectional and retrospective, shifting internal criteria, values, or conceptualization of life may render assessments over time incomparable (29). A large multicentered, randomized, prospective trial comparing outcomes of patients who have received ¹³¹Cs, ¹²⁵I, or ¹⁰³Pd radioisotopes would be helpful in guiding patient decisions but, unfortunately, is unlikely to occur. The results of this study, however, will be useful in advising patients on the acute bowel morbidity associated with ¹³¹Cs.

Back to Article Outline

Conclusion 

¹³¹Cs has recently been introduced for use in PB, and clinical information regarding its acute side-effect profile is scarce. The present study is the first to report short-term bowel morbidity after PB with ¹³¹Cs. In men undergoing PB as monotherapy with ¹³¹Cs, bowel symptoms returned to baseline by 3 months after the procedure. For patients undergoing PB with ¹³¹Cs as part of combination therapy, bowel symptoms return to their post-EBRT, pre-PB baseline by 3 months after their procedure.

Back to Article Outline

Appendix. 

Items comprising the bowel domain of the Expanded Prostate Cancer Index Composite survey instrument

Reprinted from Wei JT, Dunn RL, Litwin MS, et al. Development and validation of the EPIC for comprehensive assessment of health-related quality of life in men with prostate cancer. Urology, 56(6):899–905, © 2000.¹⁴ With permission from Elsevier.

Back to Article Outline

References 

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–249
   • View In Article
   • CrossRef
2. Cesaretti JA, Stone NN, Skouteris VM, et al. Brachytherapy for the treatment of prostate cancer. Cancer J. 2007;13:302–312
   • View In Article
   • CrossRef
3. Joseph J, Al-Qaisieh B, Ash D, et al. Prostate-specific antigen relapse-free survival in patients with localized prostate cancer treated by brachytherapy. BJU Int. 2004;94:1235–1238
   • View In Article
   • MEDLINE
   • CrossRef
4. Grimm PD, Blasko JC, Sylvester JE, et al. 10-Year biochemical (prostate-specific antigen) control of prostate cancer with (125)I brachytherapy. Int J Radiat Oncol Biol Phys. 2001;51:31–40
   • View In Article
   • Full Text
   • Full-Text PDF (16 KB)
   • CrossRef
5. Zelefsky MJ, Hollister T, Raben A, et al. Five-year biochemical outcome and toxicity with transperineal CT-planned permanent I-125 prostate implantation for patients with localized prostate cancer. Int J Radiat Oncol Biol Phys. 2000;47:1261–1266
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (108 KB)
   • CrossRef
6. Penson DF, Litwin MS, Aaronson NK. Health related quality of life in men with prostate cancer. J Urol. 2003;169:1653–1661
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (104 KB)
   • CrossRef
7. Van Gellekom MP, Moerland MA, Van Vulpen M, et al. Quality of life of patients after permanent prostate brachytherapy in relation to dosimetry. Int J Radiat Oncol Biol Phys. 2005;63:772–780
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (178 KB)
   • CrossRef
8. Ash D, Bottomley D, Al-Qaisieh B, et al. A prospective analysis of long-term quality of life after permanent I-125 brachytherapy for localized prostate cancer. Radiother Oncol. 2007;84:135–139
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (101 KB)
   • CrossRef
9. Talcott JA, Manol J, Clark JA, et al. Time course and predictors of symptoms after primary prostate cancer therapy. J Clin Oncol. 2003;21:3979–3986
   • View In Article
   • CrossRef
10. Downs TM, Sadetsky N, Pasta DJ, et al. Health related quality of life patterns in patients treated with interstitial prostate brachytherapy for localized prostate cancer—Data from CaPSURE. J Urol. 2003;170:1822–1827
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (98 KB)
    • CrossRef
11. IsoRay Medical Inc., CS-1 131Cs product information sheet and company website. Available at: http://www.isoray.com/.
    • View In Article
12. Kinsey RR. The NuDat program for nuclear data on the web, National Nuclear Data Center, Brookhaven National Laboratory. Available at http://www.nndc.bnl.gov/nndc/nudat/Accessed January 4, 2010
    • View In Article
13. Nath R, Anderson LL, Luxton G, et al. Dosimetry of interstitial brachytherapy sources: recommendations of the AAPM Radiation Therapy Committee Task Group No. 43. Med Phys. 1995;22:209–234
    • View In Article
    • MEDLINE
    • CrossRef
14. Wei JT, Dunn RL, Litwin MS, et al. Development and validation of the expanded prostate cancer index composite (EPIC) for comprehensive assessment of health-related quality of life in men with prostate cancer. Urology. 2000;56:899–905
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (789 KB)
    • CrossRef
15. Frank SJ, Pisters LL, Davis J, et al. An assessment of quality of life following radical prostatectomy, high dose external beam radiation therapy and brachytherapy iodine implantation as monotherapies for localized prostate cancer. J Urol. 2007;177:2151–2156
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (392 KB)
    • CrossRef
16. Brandeis JM, Litwin MS, Burnison CM, et al. Quality of life outcomes after brachytherapy for early stage prostate cancer. J Urol. 2000;163:851–857
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (337 KB)
    • CrossRef
17. Greene FL, Page DL, Fleming ID, et al. AJCC cancer staging manual. 6th ed.. New York, NY: Springer; 2002;pp. 309–316
    • View In Article
18. D’Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969–974
    • View In Article
    • MEDLINE
    • CrossRef
19. Heysek RV. Modern brachytherapy for treatment of prostate cancer. Cancer Control. 2007;14:238–243
    • View In Article
20. Merrick GS, Wallner KE, Butler WM. Minimizing prostate brachytherapy-related morbidity. Urology. 2003;62:786–792
    • View In Article
    • Full Text
    • Full-Text PDF (118 KB)
    • CrossRef
21. Howard A, Wallner K, Han B, et al. Clinical course and dosimetry of rectal fistulas after prostate brachytherapy. J Brachyther Int. 2001;17:37–42
    • View In Article
22. Merrick GS, Butler WM, Dorsey AT, et al. Rectal function following prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2000;48:667–674
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (597 KB)
    • CrossRef
23. Merrick GS, Butler WM, Wallner KE, et al. Late rectal function after prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2003;57:42–48
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (172 KB)
    • CrossRef
24. Merrick GS, Butler WM, Wallner KE, et al. Long-term rectal function after permanent prostate brachytherapy. Cancer J. 2007;13:95–104
    • View In Article
    • MEDLINE
    • CrossRef
25. Miller DC, Sanda MG, Dunn RL, et al. Long-term outcomes among localized prostate cancer survivors: Health-related quality-of-life changes after radical prostatectomy, external radiation, and brachytherapy. J Clin Oncol. 2005;23:2772–2780
    • View In Article
    • CrossRef
26. Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med. 2008;358:1250–1261
    • View In Article
    • CrossRef
27. Ferrer M, Suárez JF, Guedea F, et al. Health-related quality of life 2 years after treatment with radical prostatectomy, prostate brachytherapy, or external beam radiotherapy in patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008;72:421–432
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (1003 KB)
    • CrossRef
28. Davis JW, Kuban DA, Lynch DF, et al. Quality of life after treatment for localized prostate cancer: differences based on treatment modality. J Urol. 2001;166:947–952
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (56 KB)
    • CrossRef
29. Sprangers MA, Moinpour CM, Moynihan TJ, et al. Assessing meaningful change in quality of life over time: A users’ guide for clinicians. Mayo Clin Proc. 2002;77:561–571
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (130 KB)
    • CrossRef