Correlation between acute and late toxicity in 973 prostate cancer patients treated with three-dimensional conformal external beam radiotherapy.

PURPOSE: To analyze the correlation between acute and late injury in 973 prostate cancer patients treated with radiotherapy and to evaluate the effect of patient-, tumor-, and treatment-related variables on toxicity. METHODS AND MATERIALS: Of the 973 patients, 542 and 431 received definitive or postprostatectomy radiotherapy, respectively. Three-dimensional conformal radiotherapy included a six-field technique and two-dynamic arc therapy. Toxicity was classified according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. The correlation between acute and late toxicity (incidence and severity) was assessed. RESULTS: Multivariate analysis showed that age 70 Gy (p = .014), and radiotherapy duration (p = .05) correlated with greater acute urinary toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated with late rectal injury on multivariate analysis. Late urinary toxicity correlated with acute urinary events (p <.0001) and was inversely related to the use of salvage radiotherapy (p = .018). A highly significant correlation was found between the incidence of acute and late events for both rectal (p <.001) and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or greater) was predictive for the severity of late toxicity for both rectal and urinary events (p <.001). CONCLUSION: The results of our study have shown that the risk of acute reactions depends on both patient-related (age) and treatment-related (dose, technique) factors. Acute toxicity was an independent significant predictor of late toxicity. These findings might help to predict and prevent late radiotherapy-induced complications.

Health-related quality of life in patients with hormone refractory prostate cancer receiving gefitinib.

OBJECTIVES: Improvements in quality of life (QoL) and disease-related symptoms are key goals in the treatment of hormone refractory prostate cancer (HRPC). Our aim was to evaluate the impact of gefitinib on QoL of patients with HRPC. METHODS: Patients with HRPC received gefitinib 250 mg daily in addition to antiandrogen plus luteinizing hormone-releasing hormone (LHRH) analogue for at least 2 months or until disease progression. QoL was evaluated monthly by the European Organisation for Research on the Treatment of Cancer (EORTC) QLQ-C30 questionnaire. Pain was assessed daily by patients and scored by visual analogue scale and analgesic consumption in a diary. Monthly pain intensity was estimated using the McGill-Melzack questionnaire. RESULTS: Analysis of global health status according to EORTC QLQ-C30 showed an improvement of the status in only 6 patients (26%). The greatest benefit in the patients was in the subscale representing prostate-specific concerns (including appetite, pain, physical comfort, and genitourinary function). Improvement of symptoms was correlated with antiandrogen withdrawal. Global health status and QoL decreased during treatment according to tumor progression. CONCLUSIONS: Among HRPC patients treated with gefitinib, improvement of symptoms preceded evidence of biochemical response of prostate-specific antigen following antiandrogen withdrawal. These findings suggest no beneficial effect of gefitinib in QoL improvement.

Intraoperative radiotherapy for locally advanced prostate cancer: treatment technique and ultrasound-based analysis of dose distribution.

BACKGROUND: To present the technique and dose distribution of intraoperative radiotherapy (IORT) for prostate cancer. PATIENTS AND METHODS: Pelvic lymphadenectomy, prostate IORT and radical retropubic prostatectomy was performed in 11 prostate cancer patients. Prostate thickness and rectum depth were measured with intraoperative ultrasound. IORT was delivered by a mobile linear accelerator in the operating room (electron beam, 12 Gy at 90% isodose). RESULTS: The mean preoperative probability of organ-confined disease was 10% (Memorial Sloan Kettering Cancer Center nomograms). Mean prostate thickness, width and length were 3.4 cm, 4.6 and 4.9 cm, respectively. Mean rectum depth was 3.3 cm. Mean doses to the posterior prostate capsule, 5-mm lateral prostate margins and at the subsequent uretheral stump area were 4.6 Gy, 8. 7 Gy and 11.3 Gy, respectively. Maximum mean rectal dose was 4.9 Gy. CONCLUSION: IORT appeared a feasible approach for prostate cancer, showing a satisfactory dose coverage to the prostate bed with relatively low rectal dose. However, high variability in dose distribution calls for further study of patient selection criteria and dosimetry.

Gefitinib combined with endocrine manipulation in patients with hormone-refractory prostate cancer: quality of life and surrogate markers of activity.

We investigated efficacy of gefitinib in hormone-refractory prostate cancer. Between March 2003 and December 2004, 23 patients with hormone-refractory prostate cancer were assigned to receive 250 mg oral gefitinib daily in addition to antiandrogen and luteinizing hormone-releasing hormone analogue for at least 2 months or until disease progression. Patients with progression stopped antiandrogen therapy, and received gefitinib and the luteinizing hormone-releasing hormone analogue. Serum HER2 and epidermal growth factor receptor extracellular domain were evaluated every 2 months. Gefitinib treatment did not result in any objective measurable response or responses in prostate-specific antigen. Median time to progression was 70 days (33-336). Median overall survival was 293 days (25-75 percentile: 235-349). HER2 extracellular domain mean value was 9.6 ng/ml (range 6.9-13.3) at basal time and was 10.1 (range 6.0-14.1) after 2 months. Epidermal growth factor receptor mean basal value was 51.0 ng/ml (range 41.4-75.3). After 2 months of treatment the mean value was 51.1 ng/ml (range 41.5-61.4). One patient had reduction in the pain score from baseline without an increase in the analgesic score. Four patients (17%) out of 23 had pain progression with an increase from baseline of at least 25% in the analgesic score. The study was discontinued before target accrual was reached owing to lack of efficacy of the drug. Our results do not support the efficacy of gefitinib in combination with endocrine treatment for hormone-refractory prostate cancer.

Sensitivity and detection rate of a 12-core trans-perineal prostate biopsy: preliminary report.

OBJECTIVES: The various prostate biopsy methods are usually compared in terms of the diagnosis rate of prostate cancer. However, the prevalence of cancer in patients with a negative prostatic biopsy is not usually known. We determined the sensitivity and detection rate of 12-core transperineal biopsies in patients not previously investigated for prostate cancer. METHODS: We performed prostate biopsy in 63 patients (median age 67 years) before radical cystoprostatectomy for high-grade bladder cancer. We then assessed the relationships between biopsy result, prostate cancer in the surgical specimen, and other variables. RESULTS: 17.2% of patients had a positive biopsy and 54% had prostate cancer on definitive histology. Biopsy sensitivity was 32.3% overall, 75% for clinically significant cancers, and 11% for non-significant cancers. Median PSA was 1.2ng/ml, PSA levels did not correlate with the presence of prostate cancer, the presence of clinically significant cancer, bioptic diagnosis, or prostate volume. Age correlated with risk of cancer. CONCLUSIONS: According to autopsy series, the prevalence of prostate cancer is greater than 50% in males older than 60, yet low PSA levels do not reliably indicate disease absence. The sensitivity of double sextant biopsy is unsatisfactory overall (32%), but acceptable (75%) for diagnosing clinically significant cancer.

Synchronous collecting duct carcinoma and papillary renal cell carcinoma: a case report and review of the literature.

The coexistence of multiple and synchronous primary neoplasms in the same organ (including kidney) has only rarely been described in the literature. We herein present a case of collecting duct carcinoma (CDC) combined with papillary renal carcinoma (RCC) having a 57-month disease-free survival CDC is a rather rare and aggressive neoplasm of the kidney. Sharing probably the same embryological origin, synchronous or metachronous association with in situ orpapillary transitional cell carcinoma (TCC) may be found; association with RCC has been only once reported in the literature. The high incidence of c-erbB-2 oncogene amplification in CDC further characterizes this tumor as a separate entity from renal cell carcinoma, and shows some genetic characteristics in common with TCC. The histological diagnosis of Bellini CDC can be confirmed by the positive immunohistochemical staining with a collecting duct marker and distal tubule marker and negative staining with a proximal tubule marker.

Localization of avidin in superficial bladder cancer: a potentially new approach for radionuclide therapy.

OBJECTIVE: To verify whether native avidin, made radioactive through the binding with technetium-99m labeled biotin (99mTc-biotin), selectively accumulated in superficial tumor tissues following intravesical administration. METHODOLOGY: A total of fifteen patients with transitional cell bladder cancer were instilled intravesically with radiolabeled avidin. Cold biopsies were obtained from macroscopically normal and tumor tissues before transurethral resection (TUR) and the radioactivity in the samples was measured. RESULTS: Increased accumulation of radiolabeled avidin was observed in tumor tissue compared to normal bladder tissue and in some cases, remarkably high quotients of uptake (q) in tumor versus normal tissues were determined (86 and 44). The three patients instilled with a deglycosylated avidin at neutral pI, who served as a control, showed no significant uptake in either tumor or normal urothelium and no difference in relative uptake (q=1.0). CONCLUSION: This pilot study indicated that intravesical administration of radiolabeled avidin resulted in a preferential accumulation in tumor tissue compared to normal urothelium. The instillation of radiolabeled avidin warrant further investigations in order to explore the possibility to treat superficial bladder neoplasms locally by replacing 99mTc with high energy beta emitting radionuclides associated with biotin.