Patterns of outcome and toxicity after salvage prostatectomy, salvage cryosurgery and salvage brachytherapy for prostate cancer recurrences after radiation therapy: a multi-center experience and literature review.

PURPOSE: Current salvage treatments for recurrent prostate cancer after primary radiation therapy include radical prostatectomy, cryosurgery and brachytherapy. Because toxicity and failure rates are considerable, salvage treatments are not commonly performed. As most centers perform only one preferred salvage technique, the literature only describes single-center outcomes from a single salvage technique with a limited number of patients. In this overview, five high-volume Dutch centers describe their toxicity and outcome data using different salvage techniques. This provides a view on how salvage is performed in clinical practice in The Netherlands. METHODS: A total of 129 patients from five different centers in the Netherlands were retrospectively analyzed. Biochemical failure (BF) was defined as PSA >0.1 ng/ml for the salvage prostatectomy group (n = 44) and PSA nadir + 2.0 ng/ml (Phoenix definition) for the salvage cryosurgery (n = 54) and salvage brachytherapy group (n = 31). Toxicity was scored according to the Common Toxicity Criteria for Adverse events (CTCAE v3.0). RESULTS: BF occurred in 25 (81%) patients in the brachytherapy group (mean follow-up 29 ± 24 months), 29 (66%) patients in the prostatectomy group (mean follow-up 22 ± 25 months) and 33 (61%) patients in the cryosurgery group (mean follow-up 14 ± 11 months). Severe (grade >3) genitourinary and gastrointestinal toxicity was observed in up to 30% of patients in all three groups. CONCLUSION: This overview shows clinical practice of prostate cancer salvage. Significant failure and toxicity rates are observed, regardless of salvage technique. Patients should be selected with great care before offering these salvage treatment strategies.

Comparison between external beam radiotherapy (70 Gy/74 Gy) and permanent interstitial brachytherapy in 890 intermediate risk prostate cancer patients.

PURPOSE: Aim of this analysis was to compare biochemical no evidence of disease (bNED) rates in intermediate-risk prostate-cancer patients treated at two centres of excellence using different approaches: permanent interstitial brachytherapy (BT) and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A total of 890 intermediate-risk prostate-cancer patients, who were treated from 1998 to 2008, were identified in the two local databases. In Utrecht 601 patients received I-125 BT applying a dose of 144 Gy. In Vienna 289 patients were treated by EBRT, applying a local dose of 70 Gy in 105 patients and 74 Gy in 184 patients. bNED-rates (Phoenix-definition) were assessed. RESULTS: Median follow-up was 48 months (1-150). 5-Year actuarial bNED-rates were 81% for BT-patients and 75% for EBRT-patients (67% for 70 Gy and 82% for 74 Gy), respectively. In univariate analysis no difference between BT and EBRT could be detected. In multivariate analysis including tumour-stage, GleasonScore, initial PSA, hormonal therapy and treatment-centre (BT vs. EBRT) only T-stage, GleasonScore and PSA were found to be significant. Additional analysis including radiation dose showed the same outcome. CONCLUSIONS: Intermediate-risk prostate cancer patients treated by permanent interstitial brachytherapy show biochemical tumour-control-rates which are comparable to EBRT of 74 Gy.

Prostate specific antigen bounce is related to overall survival in prostate brachytherapy.

PURPOSE: To investigate the association between prostate specific antigen (PSA) bounce and disease outcome after prostate brachytherapy. METHODS AND MATERIALS: We analyzed 975 patients treated with (125)I implantation monotherapy between 1992 and 2006. All patients had tumor Stage ≤ 2c, Gleason score ≤ 7 prostate cancer, a minimum follow-up of 2 years with at least four PSA measurements, and no biochemical failure in the first 2 years. Median follow-up was 6 years. Bounce was defined as a PSA elevation of +0.2 ng/mL with subsequent decrease to previous nadir. We used the Phoenix +2 ng/mL definition for biochemical failure. Additional endpoints were disease-specific and overall survival. Multivariate Cox regression analysis was performed to adjust for potential confounding factors. RESULTS: Bounce occurred in 32% of patients, with a median time to bounce of 1.6 years. More than 90% of bounces took place in the first 3 years after treatment and had disappeared within 2 years of onset. Ten-year freedom from biochemical failure, disease-specific survival, and overall survival rates were, respectively, 90%, 99%, and 88% for the bounce group and 70%, 93%, and 82% for the no-bounce group. Only 1 patient (0.3%) died of prostate cancer in the bounce group, compared with 40 patients (6.1%) in the no-bounce group. Adjusted for confounding, a 70% biochemical failure risk reduction was observed for patients experiencing a bounce (hazard ratio 0.31; 95% confidence interval 0.20-0.48). CONCLUSIONS: A PSA bounce after prostate brachytherapy is strongly related to better outcome in terms of biochemical failure, disease-specific survival, and overall survival.

Prostate brachytherapy and second primary cancer risk: a competitive risk analysis.

PURPOSE: To assess the risk of second primary cancer (SPC) after [(125)I]iodine prostate cancer brachytherapy compared with prostatectomy and the general population. PATIENTS AND METHODS: In a cohort consisting of 1,888 patients with prostate cancer who received monotherapy with brachytherapy (n = 1,187; 63%) or prostatectomy (n = 701; 37%), SPC incidences were retrieved by linkage with the Dutch Cancer Registry. Standardized incidence rates (SIRs) and absolute excess risks (AERs) were calculated for comparison. RESULTS: A total of 223 patients were diagnosed with SPC, 136 (11%) after brachytherapy and 87 (12%) after prostatectomy, with a median follow-up of 7.5 years. The SIR for all malignancies, bladder cancer, and rectal cancer were 0.94 (95% CI, 0.78 to 1.12), 1.69 (95% CI, 0.98 to 2.70), and 0.90 (95% CI, 0.41 to 1.72) for brachytherapy and 1.04 (95% CI, 0.83 to 2.28), 1.82 (95% CI, 0.87 to 3.35), and 1.50 (95% CI, 0.68 to 2.85) for prostatectomy, respectively. Bladder SPC risk was significantly increased after brachytherapy for patients age 60 years or younger (SIR, 5.84; 95% CI, 2.14 to 12.71; AER, 24.03) and in the first 4 years of follow-up (SIR, 2.14; 95% CI, 1.03 to 3.94; AER, 12.24). Adjusted for age, the hazard ratio (brachytherapy v prostatectomy) for all SPCs combined was 0.87 (95% CI, 0.64 to 1.18). CONCLUSION: Overall, we found no difference in SPC incidence between patients with prostate cancer treated with prostatectomy or brachytherapy. Furthermore, no increased tumor incidence was found compared with the general population. We observed a higher than expected incidence of bladder SPC after brachytherapy in the first 4 years of follow-up, probably resulting from lead time or screening bias. Because of power limitations, a small increased SPC risk cannot be formally excluded.

Pretreatment nomogram to predict the risk of acute urinary retention after I-125 prostate brachytherapy.

PURPOSE: Acute urinary retention (AUR) after iodine-125 (I-125) prostate brachytherapy negatively influences long-term quality of life and therefore should be prevented. We aimed to develop a nomogram to preoperatively predict the risk of AUR. METHODS: Using the preoperative data of 714 consecutive patients who underwent I-125 prostate brachytherapy between 2005 and 2008 at our department, we modeled the probability of AUR. Multivariate logistic regression analysis was used to assess the predictive ability of a set of pretreatment predictors and the additional value of a new risk factor (the extent of prostate protrusion into the bladder). The performance of the final model was assessed with calibration and discrimination measures. RESULTS: Of the 714 patients, 57 patients (8.0%) developed AUR after implantation. Multivariate analysis showed that the combination of prostate volume, IPSS score, neoadjuvant hormonal treatment and the extent of prostate protrusion contribute to the prediction of AUR. The discriminative value (receiver operator characteristic area, ROC) of the basic model (including prostate volume, International Prostate Symptom Score, and neoadjuvant hormonal treatment) to predict the development of AUR was 0.70. The addition of prostate protrusion significantly increased the discriminative power of the model (ROC 0.82). Calibration of this final model was good. The nomogram showed that among patients with a low sum score (<18 points), the risk of AUR was only 0%-5%. However, in patients with a high sum score (>35 points), the risk of AUR was more than 20%. CONCLUSION: This nomogram is a useful tool for physicians to predict the risk of AUR after I-125 prostate brachytherapy. The nomogram can aid in individualized treatment decision-making and patient counseling.

Survival after prostate brachytherapy in patients aged 60 years and younger.

OBJECTIVE: • To compare survival after prostate brachytherapy in patients aged ≤60 years with patients aged >60 years. PATIENTS AND METHODS: • We analysed 419 locally confined prostate cancer patients, treated between 1989 and 2001 with I-125 implantation monotherapy. • Endpoints were biochemical failure (BF) according to the +2 ng/mL definition, disease-specific and overall survival. • Patients were subdivided into age ≤60 years and age >60 years. • Cox proportional-hazards regression analyses were performed to study the independent effect of age on BF and disease-specific survival. RESULTS: • The younger cohort consisted of 87 patients (21%), with smaller prostate volumes and a lower average prostate cancer risk class than the older cohort, consisting of 332 patients (79%). Mean follow-up was 9.1 years (±sd 2.8) for the younger cohort and 8.3 years (±sd 2.9) for the older cohort. • The 10-year (95% CI) freedom from BF, disease-specific survival and overall survival rates were 63% (51-75), 87% (78-96) and 81% (69-89), respectively, for the younger cohort and 46% (39-54), 83% (78-89) and 60% (54-66), respectively, for the older patient cohort. • Although a trend for better freedom from BF and disease-specific survival was observed in younger patients, the difference proved not clinically significant. CONCLUSION: • Prostate cancer risk group and the year of treatment relate to outcome, but not age. With respect to prostate cancer curability, there seems no objection to offer brachytherapy to patients aged 60 years and younger.

Influence of dose on risk of acute urinary retention after iodine-125 prostate brachytherapy.

PURPOSE: To assess the influence of dose on the risk of acute urinary retention (AUR) after iodine-125 prostate brachytherapy. METHODS AND MATERIALS: Between January 2005 and December 2008, 714 consecutive patients with localized prostate cancer were treated with iodine-125 prostate brachytherapy at our department. All patients completed four imaging studies: magnetic resonance imaging before and 4 weeks after treatment and intraoperative three-dimensional transrectal ultrasonography before and after implantation. The development of AUR was prospectively recorded. The evaluated treatment and dosimetric parameters included prostate volume, number of needles and seeds used, intra- and postoperative prostate edema, percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed dose to the prostate, minimal dose received by 90% of the prostate volume, and percentage of the urethra receiving 100%, 150%, and 200% of the prescribed dose. Logistic regression analysis was used to examine which factors were associated with AUR. RESULTS: Of the 714 patients, 57 (8.0%) developed AUR. On univariate analysis, the following treatment and dosimetric factors were significantly associated with AUR: International Prostate Symptom Score (odds ratio [OR], 2.07, per 10-point increase), preimplant prostate volume (OR, 1.06), postimplant prostate volume (OR, 1.04), number of needles used (OR, 1.09), and number of seeds used (OR, 1.03). On multivariate analysis, the only independent predictive factors for AUR were pretreatment prostate volume (OR, 1.05) and International Prostate Symptom Score (OR, 1.76, per 10-point increase). Patients with a pretreatment prostate volume >35 cm(3) had a 10.4% risk of developing AUR compared with 5.4% for those with a prostate volume of ≤ 35 cm(3). No association was found between any of the dosimetric parameters and the development of AUR. CONCLUSION: The radiation dose, within the range studied, did not influence the risk of AUR after iodine-125 prostate brachytherapy. Prostate volume and International Prostate Symptom Score were the most important predictors of AUR.

Acute urinary retention after I-125 prostate brachytherapy in relation to dose in different regions of the prostate.

PURPOSE: To assess the influence of dose in different prostate regions, and the influence of anatomic variation on the risk of acute urinary retention (AUR) after I-125 prostate brachytherapy. METHODS AND MATERIALS: In this case-control study, dosimetry and anatomy were compared between 50 patients with AUR (cases) and 50 patients without AUR (controls). Cases and controls were randomly selected from our database. The following structures were delineated on magnetic resonance imaging: prostate, urethra, peripheral zone, transitional zone, apex, base, midprostate, lower sphincter, and bladder neck. The dosimetric parameters analyzed were D(10), D(50), D(90), V(100), V(150), and V(200). The anatomic parameters analyzed were prostate protrusion into the bladder, bladder overlap, urethra angle, and urethra-bladder angle. The delineator was blinded to the patient's AUR status. Logistic regression analysis was used to investigate the association of these factors with AUR. RESULTS: The dose delivered to different regions of the prostate was not significantly associated with the risk of AUR. Only dose to the bladder neck was significantly associated with AUR (odds ratio 1.13 per 10 Gy; 95% CI 1.02;1.26; p = 0.023). Mean bladder neck D(90) was 65 Gy in AUR cases vs. 56 Gy in controls (p = 0.016), and mean bladder neck D(10) was 128 Gy vs. 107 Gy, respectively (p = 0.018). Furthermore, on univariate analysis, a larger extent of both bladder overlap and of prostate protrusion were associated with a higher risk of AUR (odds ratio 1.16; 95% CI 1.04-1.28; p = 0.005, and odds ratio 1.83; 95% CI 1.37-2.45; p < 0.001, respectively). The mean extent of prostate protrusion was 3.5 mm in AUR cases vs. 1.0 mm in controls (p < 0.001). Odds ratios did not change substantially after adjustment for potential confounders. On multivariate analysis, the extent of prostate protrusion seemed to be a stronger risk factor for AUR than bladder overlap. CONCLUSION: The risk of AUR is not associated with dose delivered to different regions of the prostate. However, a higher dose to the bladder neck and a larger extent of prostate protrusion into the bladder are risk factors for the development of AUR after I-125 prostate brachytherapy.

Loose seeds versus stranded seeds in I-125 prostate brachytherapy: differences in clinical outcome.

PURPOSE: To assess clinical outcome in terms of biochemical No evidence of disease (bNED) for patients with stranded seed implants versus loose seed implants in prostate brachytherapy. METHODS: From December 2000 until October 2006, we treated 896 T< or =2C Nx/0 Mx/0, prostate cancer patients with either stranded seed (n=538) or loose seed (n=358) I-125 implants. A total of 211 patients received a 6 months course of anti-androgen therapy, before treatment, for prostate volume reduction to <50 cc. Patients with very small and large gland volumes or a history of transurethral prostate resection, were preferably treated with stranded seeds, otherwise selection was arbitrary. RESULTS: The 5-year bNED rates (95% Confidence Interval) for stranded seed patients and loose seed patients were respectively 86% (82-90) and 90% (85-95), the total 5-year bNED rate was 87% (85-90). When adjusted for possible confounding factors in a Cox-regression analysis, type of seed was significantly associated with biochemical failure with a 43% risk reduction (hazard ratio: 0.57; 95% CI: 0.34-0.97) for loose seeds versus stranded seeds. CONCLUSIONS: These results suggest that seed-type affects clinical outcome in prostate brachytherapy, with better bNED for patients with loose seed implants.

MRI-guided robotic system for transperineal prostate interventions: proof of principle.

In this study, we demonstrate the proof of principle of the University Medical Center Utrecht (UMCU) robot dedicated to magnetic resonance imaging (MRI)-guided interventions in patients. The UMCU robot consists of polymers and non-ferromagnetic materials. For transperineal prostate interventions, it can be placed between the patient's legs inside a closed bore 1.5T MR scanner. The robot can manually be translated and rotated resulting in five degrees of freedom. It contains a pneumatically driven tapping device to automatically insert a needle stepwise into the prostate using a controller unit outside the scanning room. To define the target positions and to verify the needle insertion point and the needle trajectory, a high-resolution 3D balanced steady state free precession (bSSFP) scan that provides a T2/T1-weighted contrast is acquired. During the needle insertion fast 2D bSSFP images are generated to track the needle on-line. When the target position is reached, the radiation oncologist manually places a fiducial gold marker (small seed) at this location. In total two needle trajectories are used to place all markers. Afterwards, a high-resolution 3D bSSFP scan is acquired to visualize the fiducial gold markers. Four fiducial gold markers were placed transperineally into the prostate of a patient with a clinical stage T3 prostate cancer. In the generated scans, it was possible to discriminate the patient's anatomy, the needle and the markers. All markers were delivered inside the prostate. The procedure time was 1.5 h. This study proves that MRI-guided needle placement and seed delivery in the prostate with the UMCU robot are feasible.

Health-related quality of life up to six years after (125)I brachytherapy for early-stage prostate cancer.

PURPOSE: Health-related quality of life (HRQOL) after prostate brachytherapy has been extensively described in published reports but hardly any long-term data are available. The aim of the present study was to prospectively assess long-term HRQOL 6 years after (125)I prostate brachytherapy. METHODS AND MATERIALS: A total of 127 patients treated with (125)I brachytherapy for early-stage prostate cancer between December 2000 and June 2003 completed a HRQOL questionnaire at five time-points: before treatment and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTCQLQ-C30), and the tumor-specific EORTC prostate cancer module (EORTC-PR25). A change in a score of >/=10 points was considered clinically relevant. RESULTS: Overall, the HRQOL at 6 years after (125)I prostate brachytherapy did not significantly differ from baseline. Although a statistically significant deterioration in HRQOL at 6 years was seen for urinary symptoms, bowel symptoms, pain, physical functioning, and sexual activity (p <.01), most changes were not clinically relevant. A statistically significant improvement at 6 years was seen for mental health, emotional functioning, and insomnia (p <.01). The only clinically relevant changes were seen for emotional functioning and sexual activity. CONCLUSION: This is the first study presenting prospective HRQOL data up to 6 years after (125)I prostate brachytherapy. HRQOL scores returned to approximately baseline values at 1 year and remained stable up to 6 years after treatment. (125)I prostate brachytherapy did not adversely affect patients' long-term HRQOL.

The impact of acute urinary retention after iodine-125 prostate brachytherapy on health-related quality of life.

PURPOSE: To evaluate the impact of acute urinary retention (AUR) in patients treated with (125)I prostate brachytherapy on short- and long-term health-related quality of life (HRQOL); and to assess whether pretreatment HRQOL has additional value in the prediction of AUR. METHODS AND MATERIALS: For 127 patients treated with (125)I brachytherapy for localized prostate cancer between December 2000 and June 2003, toxicity and HRQOL data were prospectively collected. Patients received a HRQOL questionnaire at five time points: before and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30), the tumor-specific EORTC prostate cancer module (EORTC QLQ-PR25), and the American Urological Association (AUA) symptom index. RESULTS: Of 127 patients, 13 (10.2%) developed AUR. Patients with AUR had a significantly worse urinary QOL at all time points compared with patients without AUR. The mean difference over time (6 years) between both groups for the EORTC QLQ-PR25 urinary symptom score was 13.0 points (p < 0.001) and for the AUA urinary symptom score was 15.7 points (p = 0.001). Global QOL scores (EORTC QLQ-C30) over time for patients who developed AUR were significantly worse compared with patients without AUR (mean difference 6.7 points; p = 0.043). In multivariate logistic regression analysis, pretreatment International Prostate Symptom Score (p = 0.004) and neoadjuvant hormonal treatment (p = 0.034) were predictors of AUR. Quality of life did not have added predictive value. CONCLUSION: Acute urinary retention after prostate brachytherapy has a significant negative impact on patient's HRQOL up to 6 years after treatment, in terms of both global QOL measures and urinary symptom scores. Furthermore, our results suggest limited value of pretreatment HRQOL measures for the prediction of AUR.

Focal salvage guided by T2-weighted and dynamic contrast-enhanced magnetic resonance imaging for prostate cancer recurrences.

PURPOSE: Salvage treatment of the entire prostate for local recurrent cancer after primary radiotherapy is associated with high toxicity rates. Our goal was to show that, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the visualization of a recurrence, focal salvage treatment can be performed, with, potentially, a reduction in toxicity. METHODS AND MATERIALS: We performed MRI, including a DCE sequence, in 7 patients with biopsy-proven locally recurrent prostate cancer. The specific regions of interest suspect for containing tumor were delineated using DCE and T(2)-weighted MRI scans. Subsequently, focal salvage high-dose-rate brachytherapy plans were created to illustrate the principle of focal salvage. Total salvage treatment plans were also created for comparison. RESULTS: The transfer constant (K(trans)) values from the DCE were 0.33-0.67 min(-1) for areas suspect for tumor and 0.07-0.25 min(-1) for normal tissue. In 4 cases, a focal salvage plan could be generated; 93-100% of the gross tumor volume was covered with the prescribed dose, with relative sparing of the bladder, rectum, and urethra. In the total salvage plans, 24-53% of the gross tumor volume was covered, and the organs at risk received high doses. In 3 cases, a focal salvage plan could not be created because of multifocal tumor, seminal vesicle extension, or capsular extension. CONCLUSION: Focal salvage treatment plans can be created in patients with local recurrent prostate cancer after radiotherapy. DCE-MRI supports the localization of the target area. This could lead to less toxicity in patients with local recurrent prostate cancer.

Treatment outcome and toxicity after salvage 125-I implantation for prostate cancer recurrences after primary 125-I implantation and external beam radiotherapy.

PURPOSE: To evaluate the outcome and toxicity after salvage iodine-125 (125-I) implantation in patients with locally recurrent prostate cancer after primary 125-I implantation and external beam radiotherapy. METHODS AND MATERIALS: Retrospectively, 31 patients were analyzed with pathology-proven local recurrent prostate cancer after primary external beam radiotherapy (n=20) or 125-I implantation (n=11), and who had undergone salvage 125-I implantation between 1994 and 2009. For recording biochemical failure rates, the Phoenix definition and the American Society for Therapeutic Radiology and Oncology definition were applied. Toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) (Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD). RESULTS: The mean (+/-standard deviation [SD]) followup was 9 years (+/-4). The freedom from biochemical failure after 1 and 5 years' followup were 51% and 20%, respectively. Fourteen (45%) patients died of prostate cancer after a mean (+/-SD) followup of 73 (+/-39) months. Grade 1, 2, or 3 toxicity of the genitourinary tract was reported in 29%, 58% and 3% of the patients, respectively, in the acute phase, and in 16%, 39%, and 19%, respectively, in the late phase. Grade 1, 2, or 3 toxicity of the gastrointestinal tract was reported in 45%, 10%, and 0% of the patients, respectively, in the acute phase, and in 48%, 3%, and 6%, respectively, in the late phase. Grade 4 toxicity of any tract occurred in none of the patients in the acute or the late phase. CONCLUSIONS: Freedom from biochemical failure after salvage 125-I implantation for locally recurrent prostate cancer after radiotherapy is limited, and both genitourinary and gastrointestinal toxicity occur frequently.

Body mass index is not a prognostic marker for prostate-specific antigen failure and survival in Dutch men treated with brachytherapy.

OBJECTIVE: To examine the relationship between body mass index (BMI) and biochemical recurrence (BCR), cancer-specific (CSS) and overall survival (OS) in men treated with permanent prostate brachytherapy (PPB), as there is limited information on the affect of obesity on treatment outcomes for prostate cancer. PATIENTS AND METHODS: In all, 1530 patients with clinically localized prostate cancer who underwent PPB were studied. Clinical and pathological data were retrospectively obtained from medical records. The BMI was classified as normal (< 25 kg/m(2)), overweight (25-30 kg/m(2)) and obese (> or = 30 kg/m(2)). BCR was defined as a rise in PSA levels of > or = 2 ng/mL after the nadir had been reached. The cause of death was determined for each deceased patient. Patients with metastatic prostate cancer who died of any cause were classified as prostate cancer deaths. RESULTS In all, 617 (40%) patients were classified as having a normal weight, 754 (49%) overweight and 159 (10%) were obese. The Kaplan-Meier 8-year risk of BCR (95% confidence interval) was 33.3% (27.2-39.4), 29.2% (23.5-34.9) and 29.3% (12.4-46.2) for patients with a BMI of < 25 kg/m(2), 25-30 kg/m(2) and > or = 30 kg/m(2), respectively. The 8-year CSS was 88.2% (83.1-93.3), 88.6% (83.7-93.5) and 90.6% (79.9-101.4) and the 8-year OS was 70.1% (63.6-76.6), 72.9% (66.6-79.2) and 81.8% (69.3-94.3) for these three groups, respectively. Multivariate proportional hazard regression analyses of BMI and established prognostic factors for BCR confirmed the absence of any prognostic value of BMI on BCR, CSS and OS. CONCLUSIONS: BMI did not appear to have any prognostic value for BCR, CCS or OS in patients with clinically localized prostate cancer treated with PPB.

Long-term biochemical and survival outcome of 921 patients treated with I-125 permanent prostate brachytherapy.

PURPOSE: To assess long-term biochemical and survival outcome after permanent prostate brachytherapy (BT). METHODS AND MATERIALS: Data on 921 patients, treated with permanent interstitial BT monotherapy between 1989 and 2004 for or=50cc received 6 months of antiandrogen therapy before treatment. Patients were classified into risk groups with 232 defined as low-, 369 intermediate-, and 320 high-risk disease. The median follow-up was 69 months (range, 4-186 months); mean age was 67 years. RESULTS: Average 5- and 10-year biochemical no evidence of disease (bNED) rates were 79% and 57%. Average 10-year bNED rates by risk group were 88% for low-risk, 61% for intermediate-risk, and 30% for high-risk disease. The average 10-year overall and disease-specific survival rates were 59% and 82%. Ten-year overall and disease-specific survival rates by risk group were, respectively, 68% and 96% for low-risk, and 64% 87% for intermediate-risk, and 49% and 69% for high-risk disease. In multivariate Cox regression analysis, both risk group and treatment era were independent predictors of bNED and survival. CONCLUSIONS: These data on long-term survival continue to support the use of I-125 monotherapy for prostate cancer in low-risk patients and, in particular, demonstrate its efficacy in intermediate-risk patients.

[Guideline on urothelial carcinoma of the bladder]. / Richtlijn urotheelcarcinoom van de blaas.

Urothelial carcinoma of the bladder is diagnosed predominantly in people over 60 years of age. The most common symptom is haematuria. Smoking is an important risk factor (relative risk 2.5 to 3). Cystoscopy is performed whenever bladder carcinoma is suspected. The recurrence rate of a non-muscle invasive urothelial carcinoma is high (31-78% within 5 years). A single intravesical instillation with a chemotherapeutic agent within 24 hours of transurethral resection (TUR) reduces the risk of recurrence. Carcinoma in situ (CIS) should be treated as high-grade urothelial carcinoma. Standard treatment for patients with non-metastasized muscle-invasive urothelial carcinoma is cystectomy in combination with extensive lymph node dissection. There are several possibilities for urinary diversion following cystectomy, none of which are any better than the others. Bladder-sparing brachytherapy may be used in patients with solitary T1 - T2 urothelial carcinoma < 5 cm. Neoadjuvant cisplatin-containing chemotherapy prior to cystectomy in muscle-invasive carcinoma only slightly improves survival. Cisplatin-containing combination chemotherapy is the standard treatment for metastasized urothelial carcinoma.

Concurrent versus sequential chemotherapy and radiotherapy in limited disease small cell lung cancer: a retrospective comparative study.

BACKGROUND: Patients with limited-disease small cell lung cancer are treated with chemotherapy and chemotherapy combined with radiotherapy. Treatment schemes with curative intention include sequential or concurrent chemoradiotherapy, both combined with prophylactic cranial irradiation (PCI). It is unclear which scheme is superior. PATIENTS AND METHODS: Until 2001, patients received 4-5 cycles of chemotherapy. In cases of no complete response, palliative radiotherapy (RT) was given in 13 fractions of 3 Gy (CT-RT group, N=26). A total of 89 patients did not receive RT after chemotherapy (CT group). After complete response, curatively intended RT was given, of 16x2.5 Gy, concurrently with PCI of 15x2 Gy (SCT-RT group, N=111). From 2001, 40 patients received 4-5 cycles of chemotherapy concurrently with RT of 25x1.8 Gy. PCI was applied to patients with complete response (CCT-RT group). Endpoints were median survival time (MST) and overall survival (OS). RESULTS: MST of CT, CT-RT, SCT-RT and CCT-RT were 8.1, 12.5, 14.0 and 21.8 months, and 5-year OS 3.5, 4.8, 10.5 and 26.9%, respectively. Frequencies of brain metastasis after PCI in SCT-RT and CCT-RT patients were 16.4% and 8.7%, respectively. CONCLUSION: Concurrent chemoradiotherapy resulted in longer MST and higher OS than sequential chemoradiotherapy, chemotherapy with palliative radiotherapy or chemotherapy alone. Results may improve further by applying PCI at an earlier stage and increasing the RT dose.

Decline of dose coverage between intraoperative planning and post implant dosimetry for I-125 permanent prostate brachytherapy: comparison between loose and stranded seed implants.

BACKGROUND AND PURPOSE: In permanent prostate brachytherapy the dose distributions 4 weeks post implant differ from the intraoperative dose distributions. The purpose of this study is to compare intraoperative planning and post implant dosimetry for loose and stranded seed implants. MATERIALS AND METHODS: This study investigates prostate dose coverage in 389 patients with stage T1 or T2 prostate cancer treated in the years 2005, 2006 and 2007. The patients received either a loose seed or a stranded seed implant. All patients had US-based intraoperative planning and CT/MRI-based post implant dosimetry after 4 weeks. RESULTS: Intraoperative and post implant D(90) values amounted 183+/-13 Gy (mean+/-standard deviation) and 161+/-30 Gy, respectively. Decline of D(90) values (mean and 95% confidence interval) between intraoperative planning and post implant dosimetry for RAPID strand (n=67), Intersource strand (n=136) and loose selectSeeds (n=186) implants amounted to -40 (-45 to -34) Gy, -25 (-28 to -21) Gy and -15 (-18 to -21) Gy, respectively. CONCLUSIONS: The patients treated in the period 2005-2007 with stranded or loose seed implants had on average adequate D(90) values of 161+/-30 Gy. Post implant D(90) values were 22+/-27 Gy lower compared to intraoperative planning. Decline of dose coverage between intraoperative planning and post implant dosimetry was significantly larger for the stranded seed implants.

External beam radiation therapy followed by interstitial radiotherapy with iridium-192 for solitary bladder tumours: results of 111 treated patients.

BACKGROUND: Evaluation of bladder-preserving treatment protocol. OBJECTIVE: To evaluate the long-term results of iridium-192 brachytherapy-based bladder-sparing treatment strategy in patients with solitary invasive bladder tumours. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective analysis of 111 patients with solitary T1G3-T2Gall bladder tumours (< or = 5 cm), who were treated with iridium-afterloading brachytherapy between February 1988 and May 2007. INTERVENTION: After transurethral tumour resection, external beam radiotherapy (28 Gy; 12 fractions) was given, followed by brachytherapy (Iridium-192; 40 Gy). Partial cystectomy was part of the treatment strategy in nine patients. In five of those patients a T3 tumour was found, and they were included in the analysis. MEASUREMENTS: The 5-, 10- and 15-yr overall survival rate (OS); disease-specific survival rate (DSS); and disease-free survival rate (DFS) estimates were determined using the Kaplan-Meier method. RESULTS AND LIMITATIONS: Mean follow-up period was 6.2 yr (range: 0.2-16.3 yr). At the last follow-up 75 patients were alive without evidence of disease, whereas 17 patients had died without evidence of disease. Nineteen patients died of bladder cancer after a mean follow-up period of 2.9 yr (range: 0.5-9.0). OS rates at 5 yr, 10 yr, and 15 yr were 70%, 55%, and 51%, respectively. DSS rates at 5 yr, 10 yr, and 15 yr were 82%, 73% and 73%, respectively. DFS rates at 5 yr, 10 yr, and 15 yr were 60%, 47%, and 23%, respectively. Higher tumour stage (T3 vs T1) was negatively associated with DSS (hazard ratio [HR]:19.8; p=0.01) and DFS (HR: 4.67; p=0.02). No prognostic factor was found for OS. Local recurrence occurred in 27% of patients and salvage cystectomy was performed in 9% of patients. Bladder function was able to be preserved in 99 of 111 patients (89%). CONCLUSIONS: In patients with solitary stage T1-T2 bladder cancer (< or = 5 cm) who refuse radical cystectomy or who are poor candidates for major surgical procedures, this modality is a valuable treatment alternative.