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.

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.

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.

Quality of life of patients after permanent prostate brachytherapy in relation to dosimetry.

PURPOSE: To investigate changes in quality of life (QoL) after permanent prostate brachytherapy and to correlate these changes with postimplant dosimetry based on magnetic resonance (MR) images. METHODS AND MATERIALS: For this study, 127 patients with low-stage prostate cancer and treated with brachytherapy received a QoL questionnaire at five time points: before treatment and at 4 weeks, 6 months, 1 year, and 2 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer (EORTC) core questionnaire, the tumor-specific EORTC prostate cancer module, and the American Urological Association symptom index. Postimplant dosimetry was based on registered T1 spin echo transversal, T2 turbo spin echo transversal, and T2 turbo spin echo sagittal MR images and CT images taken 4 weeks after implantation of the iodine-125 seeds. Calculated parameters were prostate volume, prostate volume receiving 100% (V100) and 150% (V150) dose, dose to 90% of the prostate volume (D90), maximum dose in 1-, 2-, and 5-cm3 rectum volume, distance between prostate and anterior rectum wall, and the maximum dose in 1%, 2%, and 5% urethra volume. Analysis of variance for repeated measures was used for comparison of the means of all variables in the different questionnaires. Linear regression analysis (stepwise) was used to investigate the correlations between QoL parameters and dosimetry parameters. RESULTS: On average, only the QoL at 4 weeks after implant was significantly different from (worse than) the QoL at the other time points. Regression analysis showed a significant correlation between changes in bowel problems and the maximum dose in 2-cm3 rectum volume, between changes in urinary symptoms and prostate volume, and between changes in urinary problems and the D90 value of the prostate. CONCLUSIONS: The QoL for patients with permanent prostate implants was worse in the first months after treatment but returned to baseline values 1 year after implant. Significant correlations were found between dose distribution and QoL.

Measurement of prostate rotation during insertion of needles for brachytherapy.

BACKGROUND AND PURPOSE: The purpose of this study is to investigate whether prostate rotation due to needle insertion for prostate brachytherapy is predictable and if so, to quantify this rotation, and to see whether locking needles reduce the magnitude of prostate rotation. PATIENTS AND METHODS: The measurements are done at the beginning of the procedure for brachytherapy with a Foley catheter in situ. After a needle is inserted into the prostate, a 3D ultrasound scan is made. Then the seeds are delivered using RAPID Strands (Oncura), and the needle is withdrawn. A second 3D scan is made. The needle and seed positions are determined in these scans. To determine the rotation of the prostate, the angle between the needle and the seed trajectory is calculated. RESULTS: The prostate rotations have been measured in 16 patients, eight without the use of locking needles and eight with locking needles. In total 62 needles were inserted. The maximum rotation was 13.8 degrees and occurred in the coronal plane when no locking needles were used with a significant correlation (P<0.01, R=0.637) between the place of insertion and rotation. It was shown that the method (with or without locking needles) had a significant (P<0.001) influence on the rotation in the coronal plane. Rotations in the sagittal plane ranged from -8.5 degrees to +10.2 degrees without correlation with the insertion point of the needle or the use of locking needles. CONCLUSIONS: This study showed that prostate rotation during needle insertion for prostate brachytherapy is relatively large and unpredictable. Locking needles reduce prostate rotation in the coronal plane, but not in the sagittal plane. Minimising this rotation is necessary for accurate seed delivery, especially when a robotic implantation technique is used.

Biologically effective dose for permanent prostate brachytherapy taking into account postimplant edema.

PURPOSE: To study the influence of radiobiologic and physical parameters and parameters related to edema on the biologically effective dose (BED) for permanent prostate implants and to determine the optimal timing of seed reconstruction for BED calculation. METHODS AND MATERIALS: On the basis of the linear-quadratic model, an expression for the BED was derived, including the edema parameters. A set of parameter values was defined, and these parameter values were varied one at a time to examine the effect on the BED and the theoretically effective treatment time (t(eff)). A ratio epsilon was defined to investigate the optimal timing of seed reconstruction. RESULTS: The maximal BED decreases when the extent of lethal damage is smaller, the potential tumor doubling time is smaller, the half-life time of the seeds is shorter, and the magnitude of prostate volume increase is larger. For 125I, the optimal timing of seed reconstruction is 25 days after implantation. Seed reconstruction 1 day after the implantation results in an underestimation of the BED of at most 43%, depending on the magnitude and half-life of edema. An overestimation of the BED of at most 22% is calculated when seed reconstruction took place at the effective treatment time. CONCLUSION: The maximal BED depends strongly on the value of alpha, the potential tumor doubling time, and the choice of isotope. If prostate volume increase due to edema is not taken into account, the BED will be underestimated shortly after the implantation and overestimated if the calculations are based on images taken several months after implantation. The optimal timing of BED evaluation for 125I seed implants and typical prostate edema values is 25 days after implantation.

Cataract after total body irradiation and bone marrow transplantation: degree of visual impairment.

PURPOSE: To assess the degree of visual impairment as a result of cataract formation after total body irradiation (TBI) for bone marrow transplantation. METHODS AND MATERIALS: The data from 93 patients who received TBI in 1 or 2 fractions as a part of their conditioning regimen for bone marrow transplantation were analyzed with respect to the degree of visual impairment as a result of cataract formation. The probability to develop severe visual impairment (SVI) was determined for all patients, and the degree of visual impairment was assessed for 56 patients with stabilized cataract, using three categories: no, mild, or severe. RESULTS: For all 93 patients, the probability of developing a cataract causing SVI was 0.44. For allogeneic patients, it was 0.33 without and 0.71 with steroid treatment (p <0.001). All SVI-free probability curves reached a plateau distinct from the cataract-free curves. Apparently, cataracts developing late in the follow-up period rarely cause SVI. Of the patients with stabilized cataract, 32% had no visual impairment, 16% had mild, and 52% severe impairment. No or mild visual impairment was present in 61% of all patients with stable cataract and no steroid treatment compared with only 13% of the patients treated with steroids (p = 0.035). CONCLUSION: SVI occurs in only some of the patients (52%) with stable cataract after TBI for bone marrow transplantation in 1 or 2 fractions. Steroid treatment markedly increases the probability of developing visual problems as result of a cataract after TBI.

Three-dimensional controlled interstitial hyperthermia combined with radiotherapy for locally advanced prostate carcinoma--a feasibility study.

PURPOSE: To perform a feasibility study of three-dimensional spatially controlled interstitial hyperthermia for locally advanced prostate cancer. METHODS AND MATERIALS: Twelve patients with prostate cancer (T3NxM0) were treated with conventional external beam radiotherapy and one interstitial hyperthermia treatment. Hyperthermia was delivered with the 27-MHz multielectrode current source (MECS) interstitial hyperthermia technique on an outpatient basis. Guided by transrectal ultrasonography, 12 catheters (range 7-16) were placed in the prostate through a template. Two electrodes per probe were inserted. Thermometry (average 100 sensors) was performed from within the probes for online temperature control. Additional thermometry was done in the prostate, rectum, urethra, and bladder. Reconstruction was done by sonography. Prostate perfusion was estimated from the thermal decay at the end of treatment. The full three-dimensional temperature distribution was calculated. RESULTS: No toxicities greater than Grade 2 were recorded. A learning curve for implantation, position verification, reconstruction, and temperature simulation was experienced. Perfusion was 47 mL/100 g/min (range 30-65). The average measured temperature was T(90) (90% of the prostate reached a temperature of at least:) 39.9 degrees C and T(50) 44.1 degrees C. The average calculated temperatures were lower: T(90), 39.4 degrees C and T(50), 41.8 degrees C, because the entire prostate was taken into account. The tumor temperatures were T(90), 40.7 degrees C and T(50), 43.0 degrees C. The bladder and rectal temperatures were below the safety limits. CONCLUSION: Multielectrode-current-source interstitial hyperthermia is technically feasible and well tolerated. It was not possible to achieve the goal temperature of 42-43 degrees C because of high perfusion and implantation limitations.

Results of permanent prostate brachytherapy, 13 years of experience at a single institution.

BACKGROUND AND PURPOSE: To understand the influence of treatment techniques on the final outcome, as well as the relation of risk groups and of PSA nadir on the outcome, we reviewed our experience over more than 10 years. PATIENTS AND METHODS: Patients were treated in the period 1989 through 2000. Available for this evaluation are 351 patients. The distribution of cases by T stage was T1a, b (9%), T1c (49%), T2 (42%), and by grading G1 (58%), G2 (38%), G3 (1%) and Gx (3%). The technique of plantation of seeds varied over the years, starting with single seeds using a Mick applicator (104 patients), followed by Rapid strands without (70) and with pre-planning (177). Risk groups are categorised as low (iPSA <10 ng/ml, T1-2, grade 1), 116 patients; intermediate (iPSA 10-20 ng/ml, or grade 2-3), 114 patients; and high risk (both factors, or iPSA >20 ng/ml), 121 patients. The mean follow-up time was 50 months, median 48 and range 24-123 months. RESULTS: Overall actuarial survival at 5 and 7 years was 85 and 76%, respectively. Forty patients died, eight (2%) because of or with prostate cancer. Alive are 310 patients (88%), with 223 patients bNED (71%), 51 (16%) with PSA failure, 21 (7%) with local and 15 (5%) with distant recurrence. Total bNED was 72%. Although results are better since the introduction of Rapid strands, 79% bNED versus 54% bNED for single seeds (P = 0.14) also the increase in activity per cm(3) prostate volume accounts for this improvement. With pre-planning a significant better result (P < 0.03) is obtained as compared to single seeds or strands without planning. Categorisation into risk groups results in a significant difference (P < 0.007) of bNED with risk factors, respectively, 57% for the high, 75% for the intermediate and 89% for the low risk group. Also PSA nadir had a significant effect on outcome; patients who reach a nadir of < or =0.5 ng/ml have a 91% chance of cure. CONCLUSIONS: Results of permanent seed implantation improved with the introduction of strands, however, better staging and the increase in activity per cm(3) prostate volume also contributed to this improvement. A significant better result was obtained with pre-planning. Categorisation in risk groups corresponds very well with treatment outcome. Finally, a strong relation is found with PSA nadir.

Quality of permanent prostate implants using automated delivery with seedSelectron versus manual insertion of RAPID Strands.

BACKGROUND AND PURPOSE: To compare the quality of manually inserted RAPID Strand implants with automatically inserted selectSeed implants using volumetric and dosimetric parameters. PATIENTS AND METHODS: Patients with T1 to T2 prostate carcinoma were treated with brachytherapy. The (125)I seeds were implanted in the prostate in three different ways: manual insertion of RAPID Strands (R); insertion of selectSeeds using the seedSelectron (S); a combination of both techniques: manual insertion of RAPID Strands in the left half of the prostate and insertion of selectSeeds with the seedSelectron in the right half of the prostate (RS). The comparison is based on implant and target specific parameters. The implant specific parameters, V(100), homogeneity index (HI), and natural dose ratio (NDR), were determined at the time of implantation and four weeks later. MR images taken four weeks after the implantation were used for the calculation of the target specific parameters: D(90), HI, external index (EI), and conformation number (CN). RESULTS: We found no significant difference between the groups of implants (R, S, RS) for the implant specific parameters V(100), HI, and NDR at t(0) and neither at t(4w). For each group, the V(100) values decreased significantly with time between t(0) and t(4w). The target specific parameters D(90), HI, EI and CN were not significantly different between the groups. For the group of patients with both RAPID Strands and selectSeeds, we found a significant difference in D(90) between both halves of the prostate. CONCLUSIONS: The dosimetry parameters of a newly introduced implant technique using an automatic seed afterloader were not significantly different from the parameters of a manual insertion technique using RAPID Strands. Since either technique has its advantages and disadvantages regarding seed migration, physics quality assurance, efficiency, logistics, and ease of use, it was decided to use both techniques and to continue evaluations.

MRI-guided prostate brachytherapy with single needle method--a planning study.

BACKGROUND AND PURPOSE: Magnetic resonance image (MRI)-guided prostate brachytherapy with a conventional closed MR scanner is hampered by the limited access to the prostate. To handle this problem, we have designed a new implantation method, based on a patient lying in a closed MR scanner, a robotic device to be placed between patient's legs, and one needle with one insertion point. MATERIALS AND METHODS: The MRI-guided robotic system inserts the needle into the prostate to deliver the seeds. Each time, the needle will be retracted to the rotation point (in the body), and the insertion angle can be changed. The possible angles of the needle are limited by the geometry of the closed MR scanner and the presence of the symphysis, rectum and urethra. We have done a planning study to investigate the feasibility of this single needle method. RESULTS: The treatment plans made with the single needle method showed the possibility to cover the prostate with the prescribed dose without piercing the urethra or rectum and without pubic bone interference. The plans were comparable to the plans made for the multi parallel needle method, and the 144Gy isodose enclosed the prostate with a margin of about 2 mm. The planned angles of the needle were within the range of possible angles. CONCLUSIONS: This planning study has shown the feasibility of adequate prostate coverage with the divergent single needle method within the limited space inside the closed MR scanner.

Loco-regional conformal radiotherapy of the breast: delineation of the regional lymph node clinical target volumes in treatment position.

BACKGROUND AND PURPOSE: As the location of the regional lymph nodes (LNs) of the breast varies largely between patients and may be dependant on the position of the arm, adequate localization of these nodes is mandatory in order to fully take advantage of optimized conformal radiotherapy. For this purpose, the anatomical boundaries of the regional lymph node (LN) clinical target volumes (CTVs) for delineation on transverse CT-slices, made in treatment position, were established. PATIENTS AND METHODS: Anatomical and surgical descriptions of the regional LNs of the breast, as well as a shoulder dissection, were studied. Axial slices of a human cadaver with one arm in abduction and the other in adduction were investigated, to assess the displacement of LNs by abduction of the arm into treatment position. Based on these findings, we defined the anatomical boundaries of the regional LN CTVs visible on transverse CT-slices. RESULTS: Standard anatomical and surgical descriptions appeared to be inadequate for determination of the boundaries of the regional LN CTVs in treatment position. With abduction of the arm, a change in position of all regional LNs, except for the medial supraclavicular LNs and internal mammary LNs, was observed in the anatomical cross-sections. This was also taken into account in our delineation protocol proposal. CONCLUSIONS: Anatomically based guidelines for delineation of the regional LN CTVs for loco-regional irradiation of the breast on transverse CT-slices, made in treatment position, have been developed in this study. These could be used as a basis for conformal radiotherapy.

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.

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.

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.

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.

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.

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.

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.