Prostate Specific Membrane Antigen Positron Emission Tomography/Computerized Tomography in the Evaluation of Initial Response in Candidates Who Underwent Salvage Radiation Therapy after Radical Prostatectomy for Prostate Cancer.

PURPOSE: We assessed predictors of short-term oncologic outcomes of patients who underwent salvage radiation therapy for biochemical recurrence after robot-assisted laparoscopic radical prostatectomy without evidence of metastases on prostate specific membrane antigen positron emission tomography/computerized tomography. MATERIALS AND METHODS: We retrospectively analyzed 194 patients with biochemical recurrence after robot-assisted laparoscopic radical prostatectomy who underwent prostate specific membrane antigen positron emission tomography/computerized tomography prior to salvage radiation therapy. Patients with lymph node or distant metastases on restaging imaging or at the time of extended pelvic lymph node dissection during robot-assisted laparoscopic radical prostatectomy were excluded, as were patients who received androgen deprivation therapy during or prior to salvage radiation therapy. A multivariable logistic regression analysis was performed to assess predictors of treatment response, defined as prostate specific antigen value ≤0.1 ng/ml after salvage radiation therapy. RESULTS: Overall treatment response after salvage radiation therapy was 75% (146/194 patients). On multivariable analysis, prostate specific antigen value at initiation of salvage radiation therapy (OR 0.42, 95% CI 0.27-0.62, p <0.001), pathological T stage (pT3a vs pT2 OR 0.28, 95% CI 0.11-0.69, p=0.006; pT3b vs pT2 OR 0.26, 95% CI 0.09-0.71, p=0.009) and local recurrent disease on imaging (OR 5.53, 95% CI 1.96-18.52, p=0.003) were predictors of treatment response. CONCLUSIONS: Salvage radiation therapy in patients without evidence of metastases on prostate specific membrane antigen positron emission tomography/computerized tomography showed a good overall treatment response of 75%. Higher treatment response rates were observed in patients with lower prostate specific antigen values at initiation of salvage radiation therapy, those with local recurrent disease on imaging and those with lower pathological T stage (pT2 vs pT3a/b).

Establishing implantation uncertainties for focal brachytherapy with I-125 seeds for the treatment of localized prostate cancer.

BACKGROUND: The efficacy of focal continuous low dose-rate brachytherapy (CLDR-BT) for prostate cancer requires that appropriate margins are applied to ensure robust target coverage. In this study we propose a method to establish such margins by emulating a focal treatment in patients treated with CLDR-BT to the entire gland. MATERIAL AND METHODS: In 15 patients with localized prostate cancer, prostate volumes and dominant intra-prostatic lesions were delineated on pre-treatment magnetic resonance imaging (MRI). Delineations and MRI were registered to trans-rectal ultrasound images in the operating theater. The patients received CLDR-BT treatment to the total prostate volume. The implantation consisted of two parts: an experimental focal plan covering the dominant intra-prostatic lesion (F-GTV), followed by a plan containing additional seeds to achieve entire prostate coverage. Isodose surfaces were reconstructed using follow-up computed tomography (CT). The focal dose was emulated by reconstructing seeds from the focal plan only. The distance to agreement between planned and delivered isodose surfaces and F-GTV coverage was determined to calculate the margin required for robust treatment. RESULTS: If patients had been treated only focally, the target volume would have been reduced from an average of 40.9 cm3 for the entire prostate to 5.8 cm3 for the focal plan. The D90 for the F-GTV in the focal plan was 195±60 Gy, the V100 was 94% [range 71-100%]. The maximum distance (cd95) between the planned and delivered isodose contours was 0.48 cm. CONCLUSIONS: This study provides an estimate of 0.5 cm for the margin required for robust coverage of a focal target volume prior to actually implementing a focal treatment protocol.

Long-term survival and complications following bladder-preserving brachytherapy in patients with cT1-T2 bladder cancer.

BACKGROUND AND PURPOSE: Radical cystectomy (RC) is considered standard treatment for muscle-invasive bladder cancer (BC) and high-risk non-muscle invasive BC. In selected cases, bladder-sparing treatment using brachytherapy can be offered. We examined the outcome after brachytherapy in comparison to RC in terms of survival, complications and bladder preservation in patients with cT1G3-T2N0M0 BC. MATERIALS AND METHODS: Between 1988 and 2016, 301 patients underwent brachytherapy in two centres. Overall survival (OS) and disease specific survival (DSS) after brachytherapy and RC were assessed using Kaplan-Meier curves. Cox proportional hazards modelling was used to determine variables associated with OS and DSS. Local recurrences, bladder preservation and salvage cystectomy (SC) after brachytherapy were reported. Complications after brachytherapy, RC and SC were compared using CTCAE criteria. RESULTS: Median follow-up was 9.6 years (95% confidence interval (CI): 8.8-10.4) after brachytherapy and 10.6 years (95% CI: 10.0-11.2) after RC. Five/10-year OS was 66%/49% after brachytherapy and 68%/53% after RC (p = 0.4). Five/10-year DSS was 73%/67% after brachytherapy and 75%/65% after RC (p = 0.8). Intravesical recurrence occurred in 58/259 brachytherapy patients after which salvage cystectomy was performed in 32 patients. In total, 84% of brachytherapy-treated patients preserved their bladder. The brachytherapy cohort experienced less high grade complications than the RC cohort (p = 0.02). CONCLUSION: In selected patients with solitary, ≤5 cm cT1G3-T2N0M0 bladder tumours brachytherapy is a bladder-sparing therapy with good survival outcome and with a favourable complication rate compared to RC.

Seminal vesicle invasion on multi-parametric magnetic resonance imaging: Correlation with histopathology.

OBJECTIVES: The pre-treatment risk of seminal vesicle (SV) invasion (SVI) from prostate cancer is currently based on nomograms which include clinical stage (cT), Gleason score (GS) and prostate-specific antigen (PSA). The aim of our study was to evaluate the staging accuracy of 3T (3T) multi-parametric (mp) Magnetic Resonance Imaging (MRI) by comparing the imaging report of SVI with the tissue histopathology. The additional value in the existing prediction models and the role of radiologists' experience were also examined. METHODS: After obtaining institutional review board approval, we retrospectively reviewed clinico-pathological data from 527 patients who underwent a robot-assisted radical prostatectomy (RARP) between January 2012 and March 2015. Preoperative prostate imaging with an endorectal 3T-mp-MRI was performed in all patients. Sequences consisted of an axial pre-contrast T1 sequence, three orthogonally-oriented T2 sequences, axial diffusion weighted and dynamic contrast-enhanced sequences. We considered SVI in case of low-signal intensity in the SV on T2-weighted sequences or apparent mass while diffusion-weighted and DCE sequences were used to confirm findings on T2. Whole-mount section pathology was performed in all patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI (index test) for the prediction of histological SVI (reference standard) were calculated. We developed logistic multivariable regression models including: clinical variables (PSA, cT, percentage of involved cores/total cores, primary GS 4-5) and Partin table estimates. MRI results (negative/positive exam) were then added in the models and the multivariate modeling was reassessed. In order to assess the extent of SVI and the reason for mismatch with pathology an MRI-review from an expert genitourinary radiologist was performed in a subgroup of 379 patients. RESULTS: A total of 54 patients (10%) were found to have SVI on RARP-histopathology. In the overall cohort sensitivity, specificity, PPV and NPV for SVI detection on MRI were 75.9%, 94.7%, 62% and 97% respectively. Based on our sub-analysis, the radiologist's expertise improved the accuracy demonstrating a sensitivity, specificity, PPV and NPV of 85.4%, 95.6%, 70.0% and 98.2%, respectively. In the multivariate analysis PSA (odds ratio [OR] 1.07, p=0.008), primary GS 4 or 5 (OR 3.671, p=0.007) and Partin estimates (OR 1.07, p=0.023) were significant predictors of SVI. When MRI results were added to the analysis, a highly significant prediction of SVI was observed (OR 45.9, p<0.0001). Comparing Partin, MRI and Partin with MRI predictive models, the areas under the curve were 0.837, 0.884 and 0.929, respectively. CONCLUSIONS: MRI had high diagnostic accuracy for SVI on histopathology. It provided added diagnostic value to clinical/Partin based SVI-prediction models alone. A key factor is radiologist's experience, though no inter-observer variability could be examined due to the availability of a single expert radiologist.

Displacement patterns of stranded I-125 seeds after permanent brachytherapy of the prostate: Dosimetry in the operating room put into perspective.

BACKGROUND AND PURPOSE: The reliability of post-implant dosimetry in the OR depends on the geometrical variability of implant and anatomy after the procedure. The purpose was to gain detailed information on seed displacement patterns in different sectors of the prostate. MATERIALS AND METHODS: Of 33 patients with stranded seed implants the seed geometry and the dose distribution were compared between the situation in the OR just after the procedure, based on ultrasound images, and the situation after 1month, based on registered CT and MR images. RESULTS: There was a substantial displacement of ventral seeds of 3.8±2.5mm in caudal direction (p<0.001). Of these ventral seeds cranially located seeds moved more than caudally located seeds, 4.5±2.7mm and 2.9±2.6mm, respectively (p<0.001). The D90 in the dorsal-caudal and ventral-caudal sectors increased with respectively 44±20Gy and 29±28Gy (p<0.001) and decreased with 17±31Gy in the ventral-cranial sector (p=0.008). CONCLUSIONS: There were substantial changes in dose distribution 1month after the procedure, mainly due to implant and prostate shrinkage and displacement of ventral seed strands in caudal direction. When performing dynamic dosimetry or dosimetry at the end of the procedure the effect of these phenomena has to be taken into account when using stranded seeds.

Inter- and intra-fractional bladder motion during radiotherapy for bladder cancer: a comparison of full and empty bladders.

PURPOSE: To compare inter- and intra-fraction bladder volume variations and bladder wall motion during radiotherapy (RT) for bladder cancer with full and empty bladder protocols. MATERIALS AND METHODS: Bladder volumes, filling rates and bladder wall movement were retrospectively analyzed for 24 patients with at least 4 sets of delineable pre and post treatment cone beam CT (CBCT)-scans. Eight patients were treated with an 'empty bladder' (EB) protocol and sixteen patients with a 'full bladder' (FB) protocol. RESULTS: 24 planning CT-scans and 356 CBCT-scans (178 sets) were analyzed. The average time between pre and post irradiation CBCT was 8min (range 6-18min). Median filling rate was 1.94ml/min and did not differ between EB and FB. Random variation in bladder volume and inter-fraction wall movement was slightly but not significantly larger for FB, whereas intra-fraction bladder wall movement was slightly but not significantly smaller for FB. The largest inter- and intra-fraction bladder wall movement was found in the cranial anterior direction. CONCLUSION: Empty and full bladder protocols show similar inter- and intra-fraction wall motion, and therefore treatment choices could be purely based on organ at risk criteria.

Is there a relation between the radiation dose to the different sub-segments of the lower urinary tract and urinary morbidity after brachytherapy of the prostate with I-125 seeds?

BACKGROUND AND PURPOSE: To investigate possible relationships between the dose to the sub-segments of the lower urinary tract and lower urinary tract symptoms (LUTS) after brachytherapy of the prostate. MATERIALS AND METHODS: This study involved 225 patients treated for prostate cancer with I-125 seeds. Post-implant dose-volume histograms of the prostate, urethra, bladder wall, bladder neck and external sphincter were determined. Endpoints were the mean and the maximum International Prostate Symptom Score (IPSS) during the first 3months after the treatment. For binary analysis the patients were stratified in a group with enhanced LUTS and a group with non-enhanced LUTS. RESULTS: The dose to 0.5cm(3) of the bladder neck 'D0.5cc-blne' (p=0.002 and p=0.005), the prostate volume prior to treatment 'Vpr-0' (p=0.005 and p=0.024) and the pre-treatment IPSS (both p<0.001) were independently correlated with mean and maximum IPSS, respectively. Of the patients with a D0.5cc-blne⩾175Gy and a Vpr-0⩾42cm(3), 68% suffered from enhanced LUTS, against just 30% of the other patients (p<0.0001). CONCLUSIONS: Pre-treatment IPSS, prostate volume and dose to the bladder neck are correlated with post-implant IPSS. A combination of a large prostate and a high dose to the bladder neck is highly predictive for enhanced early LUTS.

Correlation between pre- and postimplant dosimetry for iodine-125 seed implants for localized prostate cancer.

PURPOSE: In order to evaluate implant quality for permanent prostate brachytherapy in patients with localized prostate cancer, American Brachytherapy Society and ESTRO guidelines recommend that postimplant dosimetry should be performed. To understand more about the relationship between pre- and postimplant dosimetry, a comparison was made of patients who received iodine-125 ((125)I) brachytherapy between March 1995 and the end of 2004, using a preplan technique. METHODS AND MATERIALS: CT postimplant dosimetry was available for 707 patients. Detailed dose volume analysis was performed using both preimplant ultrasound and postimplant CT data sets for a subgroup of 445 patients. The following parameters were compared: prostate volume covered by 100% of the prescription dose (Vp100), Vp150, and Vp200 and dose to 90% (D90) of the prostate. In addition, volume implanted (Vi) parameters were used to compare pre- and postimplant dosimetry. Vi parameters describe dose levels inside the patient, based on number of seeds, seed activity, and their spatial distribution relative to each other, without reference to the actual prostate volume or position. RESULTS: The mean +/- standard deviation values of preimplant (34.7 +/- 8.9 cm(3)) and postimplant (36.7 +/- 9.4 cm(3)) prostate volumes were similar. The mean (+/-standard deviation) planned D90 was 183.4 (+/-12.1) Gy while the D90 that was achieved was 145.5 (+/-20.4) Gy. Over the study period, there was a steady increase of the average D90. Postimplant CT D90 and Vp100 values correlated significantly (R = 0.84; p < 0.001). The Vi and Vp parameters all showed a strong correlation. CONCLUSIONS: In this study, we showed that there is a strong correlation between transrectal ultrasound-based preimplant and CT-based postimplant dosimetry. The excellent correlation between prostate D90 and V100 values demonstrates they are both equally valid quality indices. Vi parameters are an additional measure that can be used to assess the quality of the implant.