CyberKnife stereotactic radiotherapy as monotherapy for low- to intermediate-stage prostate cancer: Early experience, feasibility, and tolerance

Purpose: The CyberKnife (CK), a linear accelerator mounted on a robotic device, enables excellent dose conformation to the target and minimizes dose to surrounding normal tissue. It is a very suitable device for performing hypofractionated stereotactic body radiotherapy as monotherapy for low- to intermediate-risk prostate cancer patients. We report our early experience using this technique. Materials and Methods: Between June 2008 and June 2009, 10 patients underwent CK monotherapy as treatment for their prostate cancer (stage ≤T2b, Gleason score (GS) ≤7, initial PSA ≤15μg/L). The prescribed dose was 38 Gy in four daily fractions of 9.5 Gy. The International Prostate Symptom Score and Radiation Therapy Oncology Group symptom scale were prospectively administered before and at 0.5, 1, 2, 3, 6, and 12 months. Results: Median age of the patients was 71 years (range, 66-76). Three patients had stage T2a and 7a T1c disease, one patient had GS of 7, and all others had GS of 6. Median follow-up was 5.1 months. Median initial PSA was 8.3 ng/mL (range, 1.3-13.6 ng/mL). Median planning target volume delineated on computed tomography after matching with the magnetic resonance imaging scan was 107 cc (range, 42-158 cc). The median V100 of the prostate was 95.8% (range, 94.8-97.2). The D95 of the prostate was 38.3 Gy (range, 38.1-38.8 Gy). The constraints for the bladder, rectum, and urethra were well met. The International Prostate Symptom Scores after 3 months were stable compared with the pretreatment scores. Urinary and bowel Radiati

Five-year follow-up of health-related quality of life after primary treatment of localized prostate cancer

Although with earlier detection of prostate cancer more men face the long-term consequences of primary treatment, studies on the impact of treatment on long-term health-related quality of life (HRQoL) are scarce. We followed 314 men with newly diagnosed localized prostate cancer from 1 month before until 5 years after radical prostatectomy (n = 127) or external beam radiotherapy (n = 187; median follow-up = 52 months). Questionnaires addressing disease-specific (UCLA PCI) and generic (SF-36, EQ-5D) HRQoL were sent 1 month before and 6, 12 and 52 months after treatment. Repeated-measures modeling was used to study HRQoL over time. Regular urinary leakage was reported by 12% of prostatectomy patients before treatment and by 31% at the 52-month assessment. Erectile dysfunction before treatment was reported by 31% of prostatectomy patients and by 40% of radiotherapy patients; at the 52-month assessment, these percentages were 88% and 64%, respectively. Erectile dysfunction present at 1 year posttreatment can be considered permanent. Prostatectomy patients reported better generic functioning both before and after treatment than radiotherapy patients, who were on average 5.9 years older and had more comorbid conditions. General physical functioning of prostatectomy patients slightly improved over time, but declined in radiotherapy patients. The relation between age and physical scores was found to be nonlinear. The long-term physical decline in radiotherapy patients partly resulted from aging and its nonlinear impact on health, although treatment effects cannot be excluded. Scores of both patient groups remained above those of norm populations. Innovative graphs describing disease-specific and generic functions after treatment can help patients and physicians in their treatment choice

Deformation of prostate and seminal vesicles relative to intraprostatic fiducial markers

Purpose: To quantify the residual geometric uncertainties after on-line corrections with intraprostatic fiducial markers, this study analyzed the deformation of the prostate and, in particular, the seminal vesicles relative to such markers. Patients and Methods: A planning computed tomography (CT) scan and three repeat CT scans were obtained for 21 prostate cancer patients who had had three to four cylindrical gold markers placed. The prostate and whole seminal vesicles (clinical target volume [CTV]) were delineated on each scan at a slice thickness of 1.5 mm. Rigid body transformations (translation and rotation) mapping the markers onto the planning scan positions were obtained. The translation only (L-only) or both translation and rotation were applied to the delineated CTVs. Next, the residue CTV surface displacements were determined using nonrigid registration of the delineated contours. For translation and rotation of the CTV, the residues represented deformation; for L-only, the residues stemmed from deformation and rotation. L-only represented the residues for most currently applied on-line protocols. The patient and population statistics of the CTV surface displacements were calculated. The intraobserver delineation variation was similarly quantified using repeat delineations for all patients and corrected for. Results: The largest CTV deformations were observed at the anterior and posterior side of the seminal vesicles (population average standard deviation <= 3 mm). Prostate deformation was small (standard deviation <= 1 mm). The increase in these deviations when neglecting rotation (L-only) was small. Conclusion: Although prostate deformation with respect to implanted fiducial markers was small, the corresponding deformation of the seminal vesicles was considerable. Adding marker-based rotational corrections to on-line translation corrections provided a limited reduction in the estimated planning margins. (c) 2008 Elsevier Inc

FGFR3 and P53 Characterize Alternative Genetic Pathways in the Pathogenesis of Urothelial Cell Carcinoma

Fibroblast growth factor receptor 3 (FGFR3) and P53 mutations are frequently observed in bladder cancer. We here describe the distribution of FGFR3 mutations and P53 overexpression in 260 primary urothelial cell carcinomas. FGFR3 mutations were observed in 59% and P53 overexpression in 25%. Interestingly, FGFR3 and P53 alterations were mutually exclusive, because they coincided in only 5.7% of tumors. Consequently, we propose that they characterize two alternative genetic pathways in urothelial cell carcinoma pathogenesis. The genetic alterations were reflected in the pathology and the clinical outcome, i.e., FGFR3 mutations were found in low-stage/-grade tumors and were associated with a favorable disease course, whereas P53 alterations were tied to adverse disease parameters

High-dose-rate brachytherapy and external-beam radiotherapy for hormone-naïve low- and intermediate-risk prostate cancer: A 7-year experience

Purpose: To report clinical outcomes and early and late complications in 264 hormone-naïve patients with low- and intermediate-risk prostate cancer treated with high-dose-rate brachytherapy (HDR-BT) in combination with external-beam radiotherapy (EBRT). Methods and Materials: Between February 2000 and July 2007, 264 patients underwent HDR-BT in combination with EBRT as a treatment for their low- to intermediate-risk prostate cancer. The HDR-BT was performed using ultrasound-based implantation. The total HDR-BT dose was 18 Gy in 3 fractions within 24 h, with a 6-h minimum interval. The EBRT started 2 weeks after HDR-BT and was delivered in 25 fractions of 1.8 Gy to 45 Gy within 5 weeks. Results: After a mean follow-up of 74.5 months, 4 patients (1.5%) showed prostate-specific antigen progression according to the American Society for Radiation Oncology definition and 8 patients (3%) according to the Phoenix definition. A biopsy-proven local recurrence was registered in 1 patient (0.4%), and clinical progression (bone metastases) was documented in 2 patients (0.7%). Seven-year actuarial freedom from biochemical failure was 97%, and 7-year disease-specific survival and overall survival were 100% and 91%, respectively. Toxicities were comparable to other series. Conclusions: Treatment with interstitial HDR-BT plus EBRT shows a low incidence of late complications and a favorable oncologic outcome after 7 years follow-up

The effect of age on the efficacy of maintenance bacillus Calmette-Guérin relative to maintenance epirubicin in patients with stage Ta T1 urothelial bladder cancer: results from EORTC genito-urinary group study 30911

Although maintenance bacillus Calmette-Guérin (BCG) is the recommended treatment in high-risk non-muscle-invasive bladder cancer (NMIBC), its efficacy in older patients is controversial. To determine the effect of age on prognosis and treatment outcome in patients with stage Ta T1 NMIBC treated with maintenance BCG. A total of 957 patients with intermediate- or high-risk Ta T1 (without carcinoma in situ) NMIBC were randomized in European Organization for Research and Treatment of Cancer (EORTC) trial 30911 comparing six weekly instillations of epirubicin, BCG, and BCG plus isoniazid followed by three weekly maintenance instillations over 3 yr. Cox multivariate proportional hazards regression models were used to assess the relative importance of age for recurrence, progression, overall survival, and NMIBC-specific survival with adjustment for EORTC risk scores. Overall, 822 eligible patients were included: 546 patients in the BCG with or without INH arms and 276 in the epirubicin arm. In patients treated with BCG with or without INH, 34.1% were >70 yr of age and 3.7% were >80 yr. With a median follow-up of 9.2 yr, patients >70 yr had a shorter time to progression (p=0.028), overall survival (p 70 yr. In intermediate- and high-risk Ta T1 urothelial bladder cancer patients treated with BCG, patients >70 yr of age have a worse long-term prognosis; however, BCG is more effective than epirubicin independent of patient age. Intravesical bacillus Calmette-Guérin for non-muscle-invasive bladder cancer is less effective in patients >70 yr of age, but it is still more effective than epirubicin. This study was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC 30911; http://www.cancer.gov/clinicaltrials/search/view?cdrid=77075&version=HealthProfessional&protocolsearchid=12442243#StudyIdInfo_CDR0000077075

Patients' perceived burden of cystoscopic and urinary surveillance of bladder cancer: a randomized comparison

OBJECTIVE: To compare, in patients with non-muscle-invasive low-grade (pTa/pT1, G1/G2) urothelial cell carcinoma of the urinary bladder, the perceived burden of flexible cystoscopy or surveillance by microsatellite analysis (MA) in voided urine, as such patients are normally recommended to adhere to regular cysto-urethroscopic surveillance (CUS). PATIENTS AND METHODS: In all, 220 participants of a randomized trial comparing CUS and surveillance by MA were asked to complete questionnaires 1 week after cystoscopy or urine sample collection. We assessed the discomfort and pain reported during CUS, experiences with MA, and physical symptoms, medical consumption and general functioning in the week after CUS/urine sampling. RESULTS: We analysed data from 732 questionnaires (197 patients) completed after CUS and 184 (67 patients) after collecting urine. The introduction of the cystoscope was reported to cause discomfort in 39% and pain in 35% of the responses to the questionnaires; the waiting time for the results of MA was reported as burdensome in 19%. Painful micturition was significantly more frequent in the week after CUS than after MA (30% and 12%, respectively). The frequency of fever (1% and 2%) and haematuria (7% and 6%) was similar in both groups. Older patients reported significantly less pain and discomfort from cystoscopy, and this was not related to having more previous cystoscopies. CONCLUSION: CUS caused pain and discomfort in about a third of patients. The burden of MA appeared fully attributable to the waiting time for the test result. The present results are a further motivation in the search for less invasive surveillance test