Salvage high-dose-rate brachytherapy for prostate cancer persistence after brachytherapy: repeated use of a polyethylene glycol hydrogel spacer.

PURPOSE: The aim of this study is to determine if a repeated hydrogel injection in a previously irradiated patient prior to salvage high-dose-rate brachytherapy (HDR-BT) is feasible. MATERIAL AND METHODS: A 61-year-old man with an organ confined (cT1c cN0 cM0, Gleason score 3 + 3 = 6, initial prostate-specific antigen [PSA] 7.9 ng/ml) prostate cancer was previously treated with HDR-BT (3 fractions of 11.5 Gy every 2nd week) after hydrogel injection to reduce the rectal dose. Ten months after, an isolated local persistence was seen on a PSMA PET-CT. Nadir PSA was 2.0 ng/ml, 3 months after treatment and was 3.95 ng/ml by the re-treatment. Salvage therapy consisted of HDR-BT (3 fractions of 9 Gy every 2nd week) with a simultaneous integrated boost to the residual region. Again, a hydrogel injection (10 ml) was applied to reduce the rectal dose prior to the treatment. RESULTS: Both hydrogel injection and salvage HDR-BT could be applied without any significant complications or toxicity. A good PSA response was observed with a nadir of 0.42 ng/ml, twelve months after salvage therapy. Acute toxicity (max grade II) resolved within 2 days after treatment. CONCLUSIONS: The use of a hydrogel prior to salvage HDR-BT in a patient previously treated with HDR-BT is feasible and could help reduce the rectal exposure in the salvage setting.

Multiparametric ultrasound of the prostate: adding contrast enhanced ultrasound to real-time elastography to detect histopathologically confirmed cancer.

PURPOSE: We prospectively assessed whether a combined approach of real-time elastography and contrast enhanced ultrasound would improve prostate cancer visualization. MATERIAL AND METHODS: Between June 2011 and January 2012, 100 patients with biopsy proven prostate cancer underwent preoperative transrectal multiparametric ultrasound combining real-time elastography and contrast enhanced ultrasound. After initial elastographic screening for suspicious lesions, defined as blue areas with decreased tissue strain, each lesion was allocated to the corresponding prostate sector. The target lesion was defined as the largest cancer suspicious area. Perfusion was monitored after intravenous injection of contrast agent. Target lesions were examined for hypoperfusion, normoperfusion or hyperperfusion. Imaging results were correlated with final pathological evaluation on whole mount slides after radical prostatectomy. RESULTS: Of 100 patients 86 were eligible for final analysis. Real-time elastography detected prostate cancer with 49% sensitivity and 73.6% specificity. Histopathology confirmed malignancy in 56 of the 86 target lesions (65.1%). Of these 56 lesions 52 (92.9%) showed suspicious perfusion, including hypoperfusion in 48.2% and hyperperfusion in 48.2%, while only 4 (7.1%) showed normal perfusion patterns (p = 0.001). The multiparametric approach decreased the false-positive value of real-time elastography alone from 34.9% to 10.3% and improved the positive predictive value of cancer detection from 65.1% to 89.7%. CONCLUSIONS: Perfusion patterns of prostate cancer suspicious elastographic lesions are heterogeneous. However, the combined approach of real-time elastography and contrast enhanced ultrasound in this pilot study significantly decreased false-positive results and improved the positive predictive value of correctly identifying histopathological cancer.

The impact of real-time elastography guiding a systematic prostate biopsy to improve cancer detection rate: a prospective study of 353 patients.

PURPOSE: We evaluated whether real-time elastography guided biopsy improves prostate cancer detection compared to conventional systematic gray scale ultrasound guidance. MATERIALS AND METHODS: A total of 353 consecutive patients suspicious for prostate cancer were prospectively randomized for real-time elastography (178) or gray scale ultrasound (175). Each patient enrolled in the study underwent a 10-core prostate biopsy. Six lateral prostate sectors (base, mid, apex) were scanned for cancer suspicious areas, defined as stiffer blue lesions using real-time elastography and hypoechoic lesions using gray scale ultrasound. Suspicious areas were sampled by a single targeted biopsy and considered representative of a defined prostate sector. If real-time elastography or gray scale ultrasound did not visualize a suspicious area in a sector, the biopsy core was taken systematically. Imaging findings were correlated with histopathological reports. Real-time elastography and gray scale ultrasound cases were compared in terms of cancer detection rate and imaging guidance accuracy. RESULTS: Characteristics of patients undergoing real-time elastography and gray scale ultrasound, including age, prostate specific antigen, prostate volume and digital rectal examination, were not significantly different (p>0.05). Prostate cancer was detected in 160 of 353 patients (45.3%). The prostate cancer detection rate was significantly higher in patients who underwent biopsy with the real-time elastography guided approach compared to the gray scale ultrasound guided biopsy at 51.1% (91 of 178) vs 39.4% (69 of 175) (p=0.027). Overall sensitivity and specificity to detect prostate cancer was 60.8% and 68.4% for real-time elastography vs 15% and 92.3% for gray scale ultrasound, respectively. CONCLUSIONS: Sensitivity to visualize and detect prostate cancer improved using real-time elastography in addition to gray scale ultrasound during prostate biopsy. Overall sensitivity did not reach levels to omit a systematic biopsy approach.

Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria.

UNLABELLED: What's known on the subject? and What does the study add? Prostate cancer characterisation, based on laboratory findings, clinical examination and histopathological cancer features that are used to define selection criteria for AS, is not ideal. Consequently, a panel of strict or more lenient criteria to select patients for AS have been published. Studies investigating the relationship between pretreatment variables and final pathology have been done in the past showing the risk of cancer misclassification for some criteria. No study has presented an overview of cancer selection using a panel of 16 currently used AS criteria that is presented in the present study. In an exactly defined cohort after radical prostatectomy, each set of criteria was used as a diagnostic test to separate between patients with more favourable (pT2, no Gleason upgrade between biopsy grading and final pathology) and unfavourable cancer features (pT3, pN+, Gleason upgrade). To the best of our knowledge a comparison of test quality criteria for AS criteria given by sensitivity, specificity, positive and negative predictive value and likelihood ratio has not yet been reported. Moreover, we showed that tumour characterisation, by a formally sufficient 12-core biopsy, in the present dataset harboured a risk of ≈20% that unfavourable cancer features were missed regardless of whether strict or more lenient selection criteria for AS were chosen. OBJECTIVE: To evaluate final histopathological features among men diagnosed with prostate cancer eligible for low-risk (LR) or active surveillance (AS) criteria. PATIENTS AND METHODS: Retrospective application of 16 definitions for AS or LR prostate cancer to a contemporary (January 2008 to March 2011) open retropubic radical prostatectomy (RRP) series of 1745 patients. EXCLUSION CRITERIA: neoadjuvant hormones, radiotherapy, inadequate histopathological reports, <10 biopsy cores. Report on the number of men with insignificant tumours (defined as: ≤pT2, Gleason score ≤6, tumour volume <0.5 mL) and men who had unfavourable tumour characteristics on final pathology (defined as: extracapsular extension or seminal vesicle invasion or lymph node metastasis or Gleason upgrading). Sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) were calculated. RESULTS: Eligibility of patients in the final study cohort (n = 1070) varied from 5.1% to 92.7% depending on the AS or LR criteria used. Final pathology revealed 77 insignificant cancers and 578 patients who had unfavourable histopathological criteria. The detection rate for insignificant cancers on final pathology was variable ranging from 7.8% to 28.3% depending on the AS- or LR-prediction tool used; unfavourable tumour characteristics were found in up to 33.5% on final pathology. The sensitivity, specificity, PPV and NPV were 8.5-97.9%, 24.7-97.8%, 67.7-89.1% and 45.3-78.2%, respectively. The likelihood ratio to correctly identify a patient with LR disease on final pathology ranged from 1.3 to 8. CONCLUSIONS: AS or LR criteria have a significant risk of cancer misclassification. Better prediction tools are needed to improve these criteria. Re-biopsy might improve safety and should be considered more frequently in patients who opt for AS.

Comparison of real-time elastography with grey-scale ultrasonography for detection of organ-confined prostate cancer and extra capsular extension: a prospective analysis using whole mount sections after radical prostatectomy.

OBJECTIVE: •To evaluate whether transrectal real-time elastography (RTE) improves the detection of intraprostatic prostate cancer (PCa) lesions and extracapsular extension (ECE) compared with conventional grey-scale ultrasonography (GSU). PATIENTS AND METHODS: •In total, 229 patients with biopsy-proven PCa were prospectively screened for cancer-suspicious areas and ECE using GSU and RTE. •The largest tumour focus detected by RTE was defined as the index lesion. •The prostate gland was stratified into six sectors on GSU and RTE, which were compared with histopathological whole mount sections after radical prostatectomy. RESULTS: •Histopathologically, PCa was confirmed in 894 out of 1374 (61.8%) evaluated sectors and ECE was identified in 47 (21%) patients. •Of these 894 sectors, RTE correctly detected 594 (66.4%) and GSU 215 (24.0%) cancer suspicious lesions. •Sensitivity was 51% and specificity 72% using RTE compared to 18% and 90% for GSU. •RTE identified the largest side specific tumour focus in 68% of patients. •ECE was identified with a sensitivity of 38% and specificity of 96% using RTE compared to 15% and 97% using GSU. CONCLUSIONS: •Compared with GSU, RTE provides a statistically significant improvement in detection of PCa lesions and ECE. •RTE enhances GSU, although improvement is still needed to achieve a clinically meaningful sensitivity.

Assessing the vesico-urethral anastomosis after radical retropubic prostatectomy: transrectal ultrasonography can replace cystography.

OBJECTIVE: To determine if transrectal ultrasonography (TRUS) is as reliable as cystography in detecting vesico-urethral extravasation (VE) after radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: Between October 2005 and February 2006 we prospectively investigated 100 consecutive patients undergoing RRP. The vesico-urethral anastomosis was assessed 6 days after RRP by a combined investigation with TRUS and cystography. RESULTS: In most patients (79%), at 6 days after RRP the vesico-urethral anastomosis was watertight or showed minimal leakage (8%), so that the urinary catheter was removed. Different degrees of VE were detected in 21 patients. Because of small, moderate or marked VE, the indwelling catheter remained until 9, 14 and 21 days after RRP in five, three and five patients, respectively. Every VE documented by cystography was detected by TRUS beforehand; therefore TRUS showed no false-negative results in detecting a leaking anastomosis. In two patients paraurethral fluid was detected by TRUS mimicking VE, with no confirmation by cystography. CONCLUSIONS: TRUS can safely replace cystography for detecting anastomotic leakage after RRP. The decision to remove the catheter after RRP can be made without radiation exposure and use of expensive contrast medium.

Comparison of accuracy between the Partin tables of 1997 and 2001 to predict final pathological stage in clinically localized prostate cancer.

PURPOSE: We validated externally the predictive accuracy of the 2001 Partin tables and compared the 1997 and 2001 versions. MATERIALS AND METHODS: We used ROC derived AUC to test the predictive accuracy of organ confinement (OC), extraprostatic extension (ECE), seminal vesicle invasion (SVI) and lymph node involvement (LNI) of 1997 and 2001 Partin tables derived probabilities. These probabilities were defined by the pretreatment clinical stage, serum prostate specific antigen and biopsy Gleason grade of 2,139 patients treated with radical prostatectomy for clinically localized prostate cancer. RESULTS: OC, ECE, SVI and LNI were noted in 63.5%, 23.1%, 10.5% and 2.9% of cases, respectively. AUC of the 2001 tables was 0.787, 0.766, 0.775 and 0.790, for OC, ECE, SVI and LNI, respectively. These values were virtually the same as the respective 1997 Partin table AUC values, namely 0.784, 0.728, 0.791 and 0.799. CONCLUSIONS: This external validation of the 2001 Partin tables confirms good predictive accuracy of the updated tables. However, predictive accuracy in this external validation data set of 2,139 European men is virtually the same as that of the original 1997 tables. Therefore, a transition from the 1997 tables to the updated 2001 version does not appear warranted unless superior accuracy is demonstrated in other external cohorts.

Urinary concentration and tissue messenger RNA expression of monocyte chemoattractant protein-1 as an indicator of the degree of hydronephrotic atrophy in partial ureteral obstruction.

PURPOSE: To find a potential prognostic marker of the induction of hydronephrotic atrophy in congenital hydronephrosis we investigated whether the messenger (m)RNA expression and urinary concentration of monocyte chemoattractant protein-1 (MCP-1) correlated with the degree of partial ureteral obstruction, and subsequent hydronephrotic atrophy and interstitial fibrosis. MATERIALS AND METHODS: We created left partial ureteral obstruction in 96 juvenile Wistar rats and complete ureteral obstruction in 18, while 16 underwent sham operation. Depending on excretion of contrast medium into the renal pelvis after 3 days we defined 2 degrees of hydronephrosis. Renal mRNA expression of MCP-1, and renal pelvic and bladder urinary concentrations of MCP-1 were measured after 1, 2 and 3 weeks, and compared with the degree of hydronephrotic atrophy. RESULTS: Grade 1 partial ureteral obstruction resulted in mild histological changes. Grade 2 partial and complete obstruction resulted in significant hydronephrotic atrophy. MCP-1 mRNA expression in the kidney remained unchanged in grade 1 partial obstruction but was moderately increased in grade 2 partial obstruction and clearly over expressed in complete ureteral obstruction. The renal pelvic urinary concentration of MCP-1 was not higher in rats with grade 1 partial obstruction than in sham operated animals but it was significantly increased in those with grade 2 partial and complete obstruction. CONCLUSIONS: mRNA expression and the urinary concentration of MCP-1 correlate with the degree of obstruction and subsequent renal damage in hydronephrosis. They may serve as prognostic markers in children with congenital hydronephrosis.