Impact of comorbidity on health-related quality of life after prostate cancer treatment: combined analysis of two prospective cohort studies.

OBJECTIVE: To improve and individualise estimates of treatment outcomes for men diagnosed with prostate cancer, we examined the impact of baseline comorbidity on health-related quality of life (HRQL) outcomes in an analysis of two pooled, prospective cohort studies. PATIENTS AND METHODS: We studied 697 patients from three academic hospitals who received radical prostatectomy (RP), external beam radiation therapy (EBRT), or brachytherapy (BT). Measures of patient-reported bowel, urinary, and sexual symptoms along with physical and mental health were prospectively collected before treatment and 3, 12, 24, and 36 months after treatment. We assessed baseline comorbidity by the validated Index of Co-Existent Disease (ICED), abstracted from medical records. Regression mixed-models were built for each treatment group and HRQL outcome controlling for baseline age, education, marital status, risk group and patient-reported general health. RESULTS: About 71% of patients had one or more comorbid conditions at baseline. After adjusting for covariates, we found baseline comorbidity was independently associated with poorer sexual function after BT (P = 0.04) and RP (P = 0.03) but not EBRT (P = 0.35). Physical health was significantly worse for men receiving BT with more comorbidities (P = 0.02). Baseline comorbid conditions were not associated with urinary incontinence or bowel functioning. CONCLUSIONS: Comorbidity at baseline is significantly associated with poorer sexual function after prostate BT or RP. This information may help patients and their physicians anticipate outcomes after surgical and radiation treatments.

Using patient-reported outcomes to assess and improve prostate cancer brachytherapy.

OBJECTIVE: To describe a successful quality improvement process that arose from unexpected differences in control groups' short-term patient-reported outcomes (PROs) within a comparative effectiveness study of a prostate brachytherapy technique intended to reduce urinary morbidity. PATIENTS AND METHODS: Patients planning prostate brachytherapy at one of three institutions were enrolled in a prospective cohort study. Patients were surveyed using a validated instrument to assess treatment-related toxicity before treatment and at pre-specified intervals. Unexpectedly, urinary PROs were worse in one of two standard brachytherapy technique control populations (US-BT1 and US-BT2 ). Therefore, we collaboratively reviewed treatment procedures, identified a discrepancy in technique, made a corrective modification, and evaluated the change. RESULTS: The patient groups were demographically and clinically similar. In the first preliminary analysis, US-BT2 patients reported significantly more short-term post-treatment urinary symptoms than US-BT1 patients. The study's treating physicians reviewed the US-BT1 and US-BT2 treatment protocols and found that they differed in whether they used an indwelling urinary catheter. After adopting the US-BT1 approach, short-term urinary morbidity in US-BT2 patients decreased significantly. Brachytherapy procedures were otherwise unchanged. CONCLUSION: Many procedures in cancer treatments are not evaluated, resulting in practice variation and suboptimal outcomes. Patients, the primary medical consumers, provide little direct input in evaluations of their care. We used PROs, a sensitive and valid measure of treatment-related toxicity, for quality assessment and quality improvement (QA/QI) of prostate brachytherapy. This serendipitous patient-centred QA/QI process may be a useful model for empirically evaluating complex cancer treatment procedures and for screening for substandard care.

Patient-reported outcomes after 3-dimensional conformal, intensity-modulated, or proton beam radiotherapy for localized prostate cancer.

BACKGROUND: Recent studies have suggested differing toxicity patterns for patients with prostate cancer who receive treatment with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or proton beam therapy (PBT). METHODS: The authors reviewed patient-reported outcomes data collected prospectively using validated instruments that assessed bowel and urinary quality of life (QOL) for patients with localized prostate cancer who received 3DCRT (n = 123), IMRT (n = 153) or PBT (n = 95). Clinically meaningful differences in mean QOL scores were defined as those exceeding half the standard deviation of the baseline mean value. Changes from baseline were compared within groups at the first post-treatment follow-up (2-3 months from the start of treatment) and at 12 months and 24 months. RESULTS: At the first post-treatment follow-up, patients who received 3DCRT and IMRT, but not those who received PBT, reported a clinically meaningful decrement in bowel QOL. At 12 months and 24 months, all 3 cohorts reported clinically meaningful decrements in bowel QOL. Patients who received IMRT reported clinically meaningful decrements in the domains of urinary irritation/obstruction and incontinence at the first post-treatment follow-up. At 12 months, patients who received PBT, but not those who received IMRT or 3DCRT, reported a clinically meaningful decrement in the urinary irritation/obstruction domain. At 24 months, none of the 3 cohorts reported clinically meaningful changes in urinary QOL. CONCLUSIONS: Patients who received 3DCRT, IMRT, or PBT reported distinct patterns of treatment-related QOL. Although the timing of toxicity varied between the cohorts, patients reported similar modest QOL decrements in the bowel domain and minimal QOL decrements in the urinary domains at 24 months. Prospective randomized trials are needed to further examine these differences.

Race, healthcare access and physician trust among prostate cancer patients.

OBJECTIVE: To study the effect of healthcare access and other characteristics on physician trust among black and white prostate cancer patients. METHODS: A three-timepoint follow-up telephone survey after cancer diagnosis was conducted. This study analyzed data on 474 patients and their 1,320 interviews over three time periods. RESULTS: Among other subpopulations, black patients who delayed seeking care had physician trust levels that were far lower than that of both Caucasians as well as that of the black patients overall. Black patients had greater variability in their levels of physician trust compared to their white counterparts. CONCLUSIONS: Both race and access are important in explaining overall lower levels and greater variability in physician trust among black prostate cancer patients. Access barriers among black patients may spill over to the clinical encounter in the form of less physician trust, potentially contributing to racial disparities in treatment received and subsequent outcomes. Policy efforts to address the racial disparities in prostate cancer should prioritize improving healthcare access among minority groups.

Patient-reported long-term outcomes after conventional and high-dose combined proton and photon radiation for early prostate cancer.

CONTEXT: Increased radiation doses improve prostate cancer control but also increase toxicity to adjacent normal tissue. Proton radiation may attenuate adverse effects. OBJECTIVE: To determine long-term, patient-reported, dose-related toxicity. DESIGN, SETTING, AND PATIENTS: We performed a post hoc cross-sectional survey of surviving participants in the Proton Radiation Oncology Group (PROG) 9509--a randomized trial comparing 70.2 Gy vs 79.2 Gy of combined photon and proton radiation for 393 men with clinically localized prostate cancer (stage T1b-T2b, prostate-specific antigen <15 ng/mL, and no radiographic evidence of metastasis). The estimated 10-year biochemical progression rate for patients receiving standard dose was 32% (95% confidence interval, 26%-39%) compared with 17% (95% confidence interval, 11%-23%) for patients receiving high dose (P < .001). We surveyed 280 of the surviving 337 patients (83%) from April 2007 to September 2008. MAIN OUTCOME MEASURES: Prostate Cancer Symptom Indices, a validated measure of urinary incontinence, urinary obstruction and irritation, bowel problems, and sexual dysfunction, and related quality-of-life instruments. RESULTS: At a median of 9.4 years after treatment (range, 7.4-12.1 years), participants' demographic and clinical characteristics were similar. Patient-reported outcomes were reported as mean (SD) scale score for standard dose vs high dose: urinary obstruction/irritation (23.3 [13.7] vs 24.6 [14.0]; P = .36), urinary incontinence (10.6 [17.7] vs 9.7 [15.8]; P = .99), bowel problems (7.7 [7.8] vs 7.9 [9.1]; P = .70), sexual dysfunction (68.2 [34.6] vs 65.9 [34.7]; P = .65), and most other outcomes were also similar, although patients receiving standard dose whose cancers had more often progressed expressed less confidence that their cancers were under control (mean [SD] scale score for standard dose, 76.0 [25.4] vs high dose, 86.2 [17.9]; P < .001). Many patients characterized their urinary and bowel function as normal despite reporting symptoms that, for other prostate cancer patients before and early after cancer treatment, caused substantial distress. CONCLUSION: Among men with clinically localized prostate cancer, treatment with higher-dose radiation compared with standard dose was not associated with an increase in patient-reported prostate cancer symptoms after a median of 9.4 years.

Androgen deprivation-mediated cytoreduction before interstitial brachytherapy for prostate cancer does not abrogate the elevated risk of urinary morbidity associated with larger initial prostate volume.

PURPOSE: We examined whether prostate volume reduction after a short course of androgen deprivation (AD) lowered the risks of acute and chronic urinary morbidity related to radioactive seed implantation for low-risk prostate cancer. METHODS AND MATERIALS: Eighty-one patients received AD for cytoreduction before interstitial brachytherapy alone. Urinary morbidity was carefully assessed for all patients during a median followup of 53 (range, 23-78) months after treatment. Outcomes were then compared with those of a control group of 81 patients who were matched 1:1 based on identical prostate volume measured at the time of radioactive seed implant, but who had not received AD. RESULTS: Despite effective cytoreduction (median, 30% prostate volume reduction) with AD, prolonged catheterization was required significantly more often for patients who had received AD when compared with the control group of patients who were implanted at identical prostate volumes but who had not received AD (27% vs. 9%, p = 0.02). This finding remained statistically significant on multivariate analysis (p = 0.04). Surgical intervention (9% vs. 4%, p = 0.09) and subsequent urinary incontinence (4% vs. 1%, p = 0.16) were also more frequent among patients who had received AD when compared with implant volume-matched controls. CONCLUSIONS: Patients who achieved smaller prostate volumes through the use of AD maintained a significantly elevated risk (threefold) for urinary complications, commensurate with their initially large prostate volume, when compared with a control group of patients who were implanted at identical prostate volumes but who had not received AD. Therefore, patients presenting with larger prostate glands that would warrant a short course of AD before implant should be counseled accordingly when discussing options for local therapy.

Measuring perceived effects of drinking an extract of basidiomycetes Agaricus blazei Murill: a survey of Japanese consumers with cancer.

BACKGROUND: To survey cancer patients who consume an extract of the Basidiomycetes Agaricus blazei Murill mushroom (Sen-Sei-Ro) to measure their self-assessment of its effects and to develop an instrument for use in future randomized trials. METHODS: We designed, translated and mailed a survey to 2,346 Japanese consumers of Sen-Sei-Ro self-designated as cancer patients. The survey assessed consumer demographics, cancer history, Sen-Sei-Ro consumption, and its perceived effects. We performed exploratory psychometric analyses to identify distinct, multi-item scales that could summarize perceptions of effects. RESULTS: We received completed questionnaires from 782 (33%) of the sampled Sen-Sei-Ro consumers with a cancer history. Respondents represented a broad range of cancer patients familiar with Sen-Sei-Ro. Nearly all had begun consumption after their cancer diagnosis. These consumers expressed consistently positive views, though not extremely so, with more benefit reported for more abstract benefits such as emotional and physical well-being than relief of specific symptoms. We identified two conceptually and empirically distinct and internally consistent summary scales measuring Sen-Sei-Ro consumers' perceptions of its effects, Relief of Symptoms and Functional Well-being (Cronbach's alpha: Relief of Symptoms, alpha = .74; Functional Well-Being, alpha = .91). CONCLUSION: Respondents to our survey of Sen-Sei-Ro consumers with cancer reported favorable perceived effects from its use. Our instrument, when further validated, may be a useful outcome in trials assessing this and other complementary and alternative medicine (CAM) substances in cancer patients.

Long-term quality of life after definitive treatment for prostate cancer: patient-reported outcomes in the second posttreatment decade.

Definitive treatment for prostate cancer includes radical prostatectomy (RP), external beam radiation therapy (EBRT), and brachytherapy (BT). The different side effect profiles of these options are crucial factors for patients and clinicians when deciding between treatments. This study reports long-term health-related quality of life (HRQOL) for patients in their second decade after treatment for prostate cancer. We used a validated survey to assess urinary, bowel, and sexual function and HRQOL in a prospective cohort of patients diagnosed with localized prostate cancer 14-18 years previously. We report and compare the outcomes of patients who were initially treated with RP, EBRT, or BT. Of 230 eligible patients, the response rate was 92% (n = 211) and median follow-up was 14.6 years. Compared to baseline, RP patients had significantly worse urinary incontinence and sexual function, EBRT patients had worse scores in all domains, and BT patients had worse urinary incontinence, urinary irritation/obstruction, and sexual function. When comparing treatment groups, RP patients underwent larger declines in urinary continence than did BT patients, and EBRT and BT patients experienced larger changes in urinary irritation/obstruction. Baseline functional status was significantly associated with long-term function for urinary obstruction and bowel function domains. This is one of the few prospective reports on quality of life for prostate cancer patients beyond 10 years, and adds information about the late consequences of treatment choices. These data may help patients make informed decisions regarding treatment choice based on symptoms they may experience in the decades ahead.

The Health Effects of Masculine Self-Esteem Following Treatment for Localized Prostate Cancer Among Gay Men.

PURPOSE: To identify factors associated with masculine self-esteem in gay men following treatment for localized prostate cancer (PCa) and to determine the association between masculine self-esteem, PCa-specific factors, and mental health factors in these patients. METHODS: A national cross-sectional survey of gay PCa survivors was conducted in 2010-2011. To be eligible for the study, men needed to be age 50 or older, reside in the United States, self-identify as gay, able to read, write, and speak English, and to have been treated for PCa at least 1 year ago. One hundred eleven men returned surveys. RESULTS: After simultaneously adjusting for the factors in our model, men aged 50-64 years and men aged 65-74 years reported lower masculine self-esteem scores than men aged 75 years or older. Lower scores were also reported by men who reported recent severe stigma. Men who reported feeling comfortable revealing their sexual orientation to their doctor reported higher masculine self-esteem scores than men who were not. The mental component score from the SF-12 was also positively correlated with masculine self-esteem. CONCLUSION: PCa providers are in a position to reduce feelings of stigma and promote resiliency by being aware that they might have gay patients, creating a supportive environment where gay patients can discuss specific sexual concerns, and engaging patients in treatment decisions. These efforts could help not only in reducing stigma but also in increasing masculine self-esteem, thus greatly influencing gay patients' recovery, quality of life, and compliance with follow-up care.

Patients' perceptions of quality of life after treatment for early prostate cancer.

PURPOSE: Treatment for early prostate cancer produces problematic physical side effects, but prior studies have found little influence on patients' perceived health status. We examined psychosocial outcomes of treatment for early prostate cancer. PATIENTS AND METHODS: Patients with previously treated prostate cancer and a reference group of men with a normal prostate-specific antigen (PSA) level and no history of prostate cancer completed questionnaires. Innovative scales assessed behavioral consequences of urinary dysfunction, sexuality, health worry, PSA concern, perceived cancer control, treatment decision making, decision regret, and cancer-related outlook. Urinary, bowel, and sexual dysfunction were assessed with symptom indexes; health status was assessed by the Physical and Mental Summaries of the Short Form (SF-12) Health Survey. RESULTS: Compared with men without prostate cancer, prostate cancer patients reported greater urinary, bowel, and sexual dysfunction, but similar health status. They reported worse problems of urinary control, sexual intimacy and confidence, and masculinity, and greater PSA concern. Perceptions of cancer control and treatment decisions were positive, but varied by treatment: prostatectomy patients indicated the highest and observation patients indicated the lowest cancer control. Bowel and sexual dysfunction were associated with poorer sexual intimacy, masculinity, and perceived cancer control; masculinity and PSA concern were associated with greater confidence in treatment choice; and diminished sexual intimacy and less interest in PSA were associated with greater regret. CONCLUSION: The lack of change in global measures of health status after treatment for early prostate cancer obscures important influences in men's lives; cancer diagnosis and treatment complications may result in complex outcomes. Aggressive treatment may confer confidence in cancer control, yet be countered by diminished intimate relationships and masculinity, which accompany sexual dysfunction.

Time course and predictors of symptoms after primary prostate cancer therapy.

PURPOSE: Understanding the distinctive patterns of treatment-related dysfunction after alternative initial treatments for early prostate cancer (PC) may improve patients' choice of treatment and later help them adjust to its consequences. We characterized the time course of treatment complications while adjusting for potentially confounding pretreatment factors hindering other observational studies. PATIENTS AND METHODS: In a prospective cohort study of 417 men we assessed urinary, bowel, and sexual function from before primary treatment to 24 months after. To control for potential confounding, we measured sociodemographic and PC prognostic factors, medical comorbidity, and pretreatment function commonly affected by PC and its treatment. RESULTS: Patients who underwent external beam radiotherapy (EBRT), radical prostatectomy (RP), and brachytherapy (BT) differed significantly in sociodemographic factors, cancer prognostic factors, and pretreatment symptom status, especially sexual function. Urinary incontinence increased sharply after RP, while bowel problems and urinary irritation/obstruction rose after EBRT and BT. Sexual dysfunction increased in all patients, particularly after radical prostatectomy, and nerve-sparing surgical technique had little apparent benefit. There was no change in urinary function and little change in overall bowel function after 12 months, but the time course of sexual dysfunction varied by treatment and, for bowel function, by symptom. Multiple regression modeling confirmed that treatment influences all 24-month outcomes, but residual confounding persisted. CONCLUSION: Pretreatment function and the primary treatment modality for early stage PC strongly predict the affected organ systems and time course of dysfunction. With this information, patients and their physicians may refine their choice of treatment and better anticipate its consequences.

American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer.

PURPOSE: To develop a clinical practice guideline for the management of men with metastatic, recurrent, or progressive carcinoma of the prostate. The focus of this document is on the use, combinations, and timing of various forms of androgen deprivation therapy (ADT) for the palliation of men with androgen-sensitive disease. METHODS: An expert panel and writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature was performed, which included a search of online databases, bibliographic review, and consultation with content experts. A priori criteria were used to select studies for analysis and study authors were contacted when necessary. RESULTS: There were 10 randomized controlled trials, six systematic reviews, and one Markov model available to inform the guidelines. CONCLUSION: A full discussion between practitioner and patient should occur to determine which therapy is best for the patient. Bilateral orchiectomy or luteinizing hormone releasing hormone agonists are the recommended initial treatments. Nonsteroidal antiandrogen therapy may be discussed as an alternative, but steroidal antiandrogens should not be offered as monotherapy. Patients willing to accept the increased toxicity of combined androgen blockage for a small benefit in survival should be offered nonsteroidal antiandrogen in addition to castrate therapy. Until data from studies using modern medical diagnostic/biochemical tests and standardized follow-up schedules become available, no specific recommendations can be issued regarding the question of early versus deferred ADT. A discussion about the pros and cons of early versus deferred ADT should occur.

Quality of life in prostate cancer.

Little more than a decade ago, measurements of health-related quality of life (HRQOL) of prostate cancer patients began to enter the medical literature. Initially controversial and of little apparent relevance to clinical care, HRQOL has grown in importance in prostate cancer to the point that providing it in treatment discussions is now considered a core element of clinical care. The United States (US) Food and Drug Administration has used it to make approval decisions for prostate cancer drugs, and Europeans have endorsed its central role in prostate cancer as well [Altwein J, Ekman P, Barry M, et al. How is quality of life in prostate cancer patients influenced by modern treatment? The Wallenberg symposium. Urology 1997, 49(Suppl 4A), 66-76.]. We propose to characterise the treatment dilemmas facing patients with prostate cancer, the clinical relevance of HRQOL research, its central conceptual elements, the characteristics of some available instruments to measure it, the use of HRQOL in clinical studies, and some of the remaining challenges we have identified during our 13 years in the field.

Patient-reported acute gastrointestinal toxicity in men receiving 3-dimensional conformal radiation therapy for prostate cancer with or without neoadjuvant androgen suppression therapy.

OBJECTIVE: To investigate the impact of 2 months of neoadjuvant and 2 months of concurrent hormonal therapy on the acute gastrointestinal (GI) toxicities associated with 3-dimensional conformal radiation therapy (3D-CRT) for prostate adenocarcinoma. METHODS: The study cohort consisted of 80 men who underwent 3D-CRT with (n=40) or without (n=40) neoadjuvant and concurrent hormonal therapy. Computerized tomography-based planning occurred after neoadjuvant hormonal therapy. All patients completed a previously validated, quality-of-life self-assessment tool on 7 GI symptoms, including diarrhea, urgency, pain, rectal bleeding, cramping, mucus, and tenesmus, at baseline and weekly during radiation therapy. RESULTS: Patients who received hormonal therapy were more likely to have T2b, T2c, T3a, or T3b (P<0.001) or Gleason score 7, 8, or 9 (P=0.02) disease compared to those that did not. The dose delivered to the planning target volume was 70 Gy for both groups. Median radiation treatment volume was numerically smaller for the hormone group but not to a statistically significant degree (949 vs. 1043 cc, P=0.30). Patients who received hormonal therapy had less rectal pain (P<0.01) and tenesmus (P=0.02) but more rectal mucus (P=0.03) compared to those who did not. CONCLUSIONS: Prostate gland volume reduction after androgen suppression therapy may reduce patient-reported acute GI toxicities associated with 3D-CRT for prostate cancer.

Suspected spinal cord compression in cancer patients: a multidisciplinary risk assessment.

Investigators involved in this study sought to identify independent clinical predictors of spinal cord compression (SCC) in cancer patients by analyzing a comprehensive set of potential risk factors based on the results of spine magnetic resonance imaging (MRI). In all, the investigators analyzed 136 episodes of suspected SCC among 134 cancer patients evaluated with spine MRI. Each subject was interviewed within 7 days of the spine MRI to collect accurate self-reported symptom data. Neurologic examination data were detailed by the physician examining the subject prior to the spine MRI; uniform demographic and clinical information regarding the subject's cancer history was abstracted from the medical record. Multivariable logistic regression analysis was used to identify independent predictors of SCC. Clinically significant SCC was defined as thecal sac compression (TSC), which occurred in 50 episodes (37%). Four independent predictors of TSC were identified and included information from the neurologic examination (abnormal neurologic examination), subject-reported symptoms (middle or upper back pain), and the oncologic history (known vertebral metastases and metastatic disease at initial diagnosis). These four predictors stratified patients experiencing episodes into subgroups with varying risks of TSC, ranging from 8% (no risk factors) to 81% (three or four risk factors). These results confirmed earlier retrospective studies indicating that the evaluation of cancer patients with suspected SCC should be based upon clinical information that includes cancer-related history, symptom data,and the presence of pertinent neurologic signs. These predictors may help clinicians to assess risk in this patient population.