What is the optimal duration of androgen deprivation therapy in prostate cancer patients presenting with prostate-specific antigen levels > 20 ng/ml?

PURPOSE: To evaluate the optimal duration of androgen deprivation therapy (ADT) in patients with prostate cancer treated with external beam radiotherapy (EBRT), who present with PSA levels > 20 ng/mL. METHODS AND MATERIALS: A total of 307 patients presenting with a PSA > 20 ng/ml were treated with EBRT and ADT. The cohort was divided into four groups according to the duration of ADT: Group 1 received < 6 months (n = 71), group 2 received 6-12 months (n = 80), group 3 received 12-24 months (n = 72), and group 4 received > 24 months (n = 84) of ADT. The endpoints analyzed were biochemical control (bNED), overall survival (OS) and cause-specific survival (CSS). Statistical analysis was conducted using Kaplan-Meier estimates and Cox regression models. RESULTS: Compared to patients who received < 6 months of ADT, patients treated with 12-24 months or > 24 months of ADT experienced significantly improved bNED (p = 0.01 and p < 0.0001, respectively). Cause-specific survival with ADT durations 12-24 and > 24 months were significantly higher compared to < 6 months (p < 0.007 and 0.024, respectively). Overall survival with ADT durations > 24 months was also significantly higher compared to < 6 months (p = 0.0025). CONCLUSIONS: The present analysis supports the hypothesis that longer durations of ADT improves bNED, CSS and OS in patients presenting with a PSA > 20 ng/ml.

Prospective evaluation of the prevalence and severity of fatigue in patients with prostate cancer undergoing radical external beam radiotherapy and neoadjuvant hormone therapy.

OBJECTIVE: To prospectively evaluate the prevalence and severity of fatigue and its impact on quality of life (QOL) during and after radical external beam radiotherapy (RT) for prostate cancer. METHOD AND MATERIALS: Twenty-eight men with prostate cancer undergoing RT over 6-8 consecutive weeks were prospectively accrued. The Brief Fatigue Inventory (BFI), a validated fatigue assessment tool, was administered at five time points: baseline (week 1), middle of RT (week 3-4), end of RT (last week of RT), and follow-up (median 6.5 weeks after RT). The BFI contained nine questions, each using 0-10 ratings to quantify fatigue severity and interference with six QOL domains. The prevalence of moderate-severe fatigue was plotted as a function of time. Mean sum and subscale scores at each time point were compared to baseline scores using Wilcoxon tests. Linear regression analyses were performed to assess associations between fatigue scores and age, tumor and treatment characteristics. RESULTS: The median age was 69 years (range 57-84), Gleason score 7 (range 6-10), and presenting PSA 9.0 ng/mL (range 2.5 ng/mL-103.0 ng/mL). Patients were treated once daily to a median dose of 74 Gy (range 60 Gy-78 Gy) over a median of 37 fractions (range 30-39). Hormone therapy was used in all patients (median duration 12.2 months). The prevalence of moderate-severe present fatigue increased from 7% at baseline to 8% at mid-RT and 32% at RT completion. Compared to baseline (mean score 11.5), fatigue increased significantly mid-RT (mean score 14.6, p = 0.03) and peaked at the end of RT (mean score 23.5, p = 0.001). Fatigue significantly interfered with walking ability, normal work, daily chores, and enjoyment of life only at the end of RT. After RT completion, fatigue improved but remained higher compared to baseline at 6.5 weeks of follow-up (mean score 15.0, p = 0.02). On linear regression analysis, age, Gleason score, PSA, T-stage, hormone therapy duration, RT dose and fractions were not significantly associated with mean fatigue scores. CONCLUSION: Patients undergoing 6-8 weeks of RT experienced significant fatigue adversely affecting QOL persisting after therapy completion. Since walking ability was not affected until the end of RT, a walking exercise intervention to combat fatigue is likely feasible and is being investigated.

Endoscopic response predicts for survival and organ preservation after primary chemoradiotherapy for esophageal cancer.

PURPOSE: To determine the role of endoscopic surveillance in predicting organ preservation and survival after primary chemoradiotherapy (CRT) for esophageal cancer. MATERIALS AND METHODS: Fifty-six consecutive patients with nonmetastatic esophageal cancer were treated with primary CRT between May 1993 and April 1999 with curative intent and subsequent surveillance with endoscopy and CT scans. Patients with residual disease on endoscopy and/or CT 6 weeks after CRT were considered for immediate esophagectomy. The remaining patients continued endoscopic surveillance and were considered for esophagectomy only when local relapse was detected. Five-year survival was estimated using the Kaplan-Meier method, and univariate and multivariate analyses were performed to identify significant factors associated with disease-specific survival. RESULTS: With a median follow-up of 62 months, the 5-year overall and disease-specific survival was 30% (95% confidence interval [CI]: 17%-43%) and 37% (95% CI: 22%-50%), respectively. Fourteen of 24 (58%) patients who survived more than 2 years did not require an esophagectomy. On univariate analysis, favorable prognostic factors for disease-specific survival were female gender (p = 0.026), CT-defined N(0) status (p = 0.027), and negative endoscopy at 6 weeks after CRT (p < 0.0001). On multivariate analysis, N(0) status and negative endoscopy after CRT remained significant (p = 0.03 and p < 0.0001, respectively) for disease-specific survival. On multivariate analysis for overall survival, female gender and negative endoscopy were significant (p = 0.35 and p < 0.001, respectively). The hazard ratios for disease-specific survival with positive nodal status and positive endoscopy were 2.44 (95% CI: 1.14-5.3) and 5.18 (95% CI: 2.3-11.6), respectively. CONCLUSIONS: Endoscopic response after primary CRT for esophageal cancer was the most significant predictive factor for overall and disease-specific survival. Regular endoscopic surveillance after CRT achieved survival rates comparable to other strategies and successfully preserved the esophagus in the majority of patients who survived more than 2 years.

Is there a role for acupuncture in the symptom management of patients receiving palliative care for cancer? A pilot study of 20 patients comparing acupuncture with nurse-led supportive care.

PURPOSE: A pilot study to document changes in symptoms after acupuncture or nurse-led supportive care in patients with incurable cancer. METHODS: Patients receiving palliative care with estimated survival of at least 3 months were screened with the Edmonton Symptom Assessment System (ESAS). Patients (n=20) with significant symptoms were randomised to receive weekly acupuncture or nurse-led supportive care for 4 weeks. ESAS scores were obtained before and after each treatment, and weekly for 6 weeks after treatment by telephone. RESULTS: 42 of 170 patients screened were eligible. 20 gave consent for recruitment. The compliance rate was 90% for acupuncture and 80% for nurse-led supportive care. Total symptom scores were reduced by an average of 22% after each acupuncture visit and by 14% after each supportive care visit. Compared with baseline, ESAS scores at the end of the follow-up period were reduced by 19% for the acupuncture arm and 26% for nurse-led supportive care. CONCLUSION: Patients appear to benefit from incorporating acupuncture in the treatment of advanced incurable cancer. Acupuncture was well tolerated with no significant or unexpected side effects. Acupuncture had an immediate effect on all symptoms, whereas nurse-led supportive care had a larger impact 6 weeks after the final session. Both interventions appear helpful to this population and warrant further study.

Extreme-risk prostate adenocarcinoma presenting with prostate-specific antigen (PSA)>40 ng/ml: prognostic significance of the preradiation PSA nadir.

PURPOSE: To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml. METHODS AND MATERIALS: A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration and pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined. RESULTS: Median follow-up time was 6.45 years (range, 0.09-15.19 years). Actuarial bDFS, PCSS, and OS rates at 5 years were 39%, 87%, and 78%, respectively, and 17%, 64%, and 45%, respectively, at 10 years. On multivariate analysis, the pre-RT PSA level (≤0.1 versus >0.1 ng/ml) was the single most significant prognostic factor for bDFS (p=0.033) and OS (p=0.018) rates, whereas age, T stage, Gleason score, and ADT duration (≤6 versus >6 months) were not predictive of outcomes. CONCLUSION: In prostate cancer patients with high presenting PSA levels, >40 ng/ml, treated with combined modality, neoadjuvant ADT, and RT, the pre-RT PSA nadir, rather than ADT duration, was significantly associated with improved survival. This observation supports the use of neoadjuvant ADT to drive PSA levels to below 0.1 ng/ml before initiation of RT, to optimize outcomes for patients with extreme-risk disease.

Prospective evaluation of a 12-week walking exercise program and its effect on fatigue in prostate cancer patients undergoing radical external beam radiotherapy.

OBJECTIVE: To evaluate tolerability and compliance to a walking exercise program and its effect on fatigue during and after radical external beam radiation therapy (EBRT) for prostate cancer. METHODS: A total of 50 subjects with prostate cancer undergoing EBRT over 6 to 8 weeks were prospectively accrued to an exercise intervention group, matched for age and clinical characteristics to 30 subjects in a historical control group who underwent EBRT with no specific exercise intervention. Starting 1 week before EBRT, exercise participants performed moderate-intensity walking targeting 60% to 70% age-predicted maximum heart rate, at least 20 min/d, 3 d/wk over 12 weeks. The Brief Fatigue Inventory was administered at baseline, mid-EBRT (week 3-4), end-EBRT (week 6-8), and 6 months post-EBRT. RESULTS: Of 50, 42 (84%) of exercise participants completed the walking program. There were no cardiovascular complications, musculoskeletal injuries, or other adverse events. A total of 89% subjects reported "Good-Excellent" satisfaction during and up to 6 months post-EBRT. Fatigue in control subjects escalated from baseline to end-EBRT, remaining high at 6 months post-EBRT (P[r] = 0.03). In contrast, mean total fatigue scores in exercise subjects were stable from baseline up to 6 months post-EBRT (P = 0.52). Trends for higher fatigue interference with quality of life were observed in the control group as compared with the exercise group. CONCLUSIONS: Moderate-intensity walking exercise during radical EBRT is safe and feasible. The high convenience and satisfaction ratings, in conjunction with the observed fatigue trends, indicate that this activity has the potential to attenuate fatigue and improve quality of life for patients with localized prostate cancer undergoing curative therapy.

Prognostic significance of blood transfusions in patients with esophageal cancer treated with combined chemoradiotherapy.

OBJECTIVE: Anemia occurs commonly in patients with esophageal cancer. This study evaluates the effect of blood transfusion on survival outcomes in patients with esophageal cancer treated with combined chemoradiotherapy (CRT). PATIENTS AND METHODS: Fifty-six consecutive patients with unresectable esophageal cancer received 50 Gy in 25 fractions over 5 weeks concurrent with cycles 2 and 3 of cisplatin and 5-fluorouracil chemotherapy. Data on hemoglobin before and during radiation therapy (RT) and blood transfusion use were abstracted by chart review. Each patient had a blood count before every chemotherapy cycle, and the test was repeated if the blood count was low. Five-year Kaplan-Meier overall survival (OS) and relapse-free survival (RFS) estimates were compared according to pre-RT hemoglobin levels and transfusion use. Multivariate analysis using Cox regression modeling was performed to determine the prognostic significance of pre-RT hemoglobin and transfusion use on survival outcomes. RESULTS: The 5-year OS and RFS rates were 30% and 37%, respectively. Seventeen patients (30%) received transfusions during CRT. Among 18 patients (32%) with a hemoglobin of < or =12 g/dL at the start of RT, 9 received transfusions. Pre-RT hemoglobin levels of < or =12 g/dL were strongly associated with the use of blood transfusions (P = 0.03). Five-year Kaplan-Meier OS was 65% versus 21% in patients treated with, versus without, a transfusion (P = 0.006). On multivariate analysis, the use of blood transfusion was associated with improved OS (hazard ratio, 0.26; 95% confidence interval, 0.09-0.75, P = 0.01). CONCLUSIONS: The use of blood transfusion is a significant treatment-related factor associated with improved survival in patients undergoing CRT for esophageal cancer.

Examining time intervals between diagnosis and treatment in the management of patients with limited stage small cell lung cancer.

OBJECTIVE: To examine time intervals between diagnosis and treatment of limited stage small cell lung cancer (L-SCLC) and to evaluate its effect on clinical outcomes. MATERIALS AND METHODS: Data on 166 patients with L-SCLC referred to a regional cancer center between January 1991 and December 1999 were analyzed. The time intervals studied were defined as: interval A, first abnormal chest x-ray to pathologic diagnosis: interval B, diagnosis to first oncology consultation; interval C, oncology consultation to first day of thoracic radiotherapy (RT); interval D, oncology consultation to first day of chemotherapy; and interval E, first day of chemo to first day of RT. Cox proportional hazards models were used to examine associations between the time intervals and thoracic relapse (TR) and overall survival (OS) outcomes. Logistic regression analysis was used to model associations between time and complete response (CR) rates. RESULTS: The median time duration of intervals A to E were 20, 12, 63.5, 15, and 48 days, respectively. When time was analyzed as a continuous variable, no statistically significant association between the interval lengths and outcomes studied was observed. Dichotomizing each interval using the median value as cut-off revealed that interval A >20 days was significantly associated with improved CR (odds ratio = 3.573; P = 0.027) whereas interval B >12 days was associated with a trend toward lower CR (odds ratio = 0.348; P = 0.073). CONCLUSIONS: Short median times from first abnormal chest x-ray to diagnosis and from diagnosis to oncology consultation indicate that L-SCLC patients were diagnosed and referred promptly in the community setting. OS and TR appeared independent of the time intervals analyzed. Individual variations in disease presentation and tumor biology may explain the observed associations between early pathologic diagnosis and inferior CR rates.