Variation in the management of cT1 renal cancer by surgical hospital volume: A nationwide study.

Objectives: To analyse variation in clinical management of cT1 renal cell carcinoma (RCC) in the Netherlands related to surgical hospital volume (HV). Materials and methods: Patients diagnosed with cT1 RCC during 2014-2020 were identified in the Netherlands Cancer Registry. Patient and tumour characteristics were retrieved. Hospitals performing kidney cancer surgery were categorised by annual HV as low (HV < 25), medium (HV = 25-49) and high (HV > 50). Trends over time in nephron-sparing strategies for cT1a and cT1b were evaluated. Patient, tumour and treatment characteristics of (partial) nephrectomies were compared by HV. Variation in applied treatment was studied by HV. Results: Between 2014 and 2020, 10 964 patients were diagnosed with cT1 RCC. Over time, a clear increase in nephron-sparing management was observed. The majority of cT1a underwent a partial nephrectomy (PN), although less PNs were applied over time (from 48% in 2014 to 41% in 2020). Active surveillance (AS) was increasingly applied (from 18% to 32%). For cT1a, 85% received nephron-sparing management in all HV categories, either with AS, PN or focal therapy (FT). For T1b, radical nephrectomy (RN) remained the most common treatment (from 57% to 50%). Patients in high-volume hospitals underwent more often PN (35%) for T1b compared with medium HV (28%) and low HV (19%). Conclusion: HV is related to variation in the management of cT1 RCC in the Netherlands. The EAU guidelines have recommended PN as preferred treatment for cT1 RCC. In most patients with cT1a, nephron-sparing management was applied in all HV categories, although differences in applied strategy were found and PN was more frequently used in high HV. For T1b, high HV was associated with less appliance of RN, whereas PN was increasingly used. Therefore, closer guideline adherence was found in high-volume hospitals.

[Pneumothorax as an early indication for a genetic disorder]. / Pneumothorax als vroege aanwijzing voor een erfelijke aandoening.

BACKGROUND: Several hereditary disorders, with highly variable and sometimes difficult to recognize manifestations, can present with a spontaneous pneumothorax. Options to perform DNA-testing have changed rapidly, as a result of which physicians of diverse disciplines are coming into contact with hereditary disorders. CASE DESCRIPTION: Two patients with a history of multiple spontaneous pneumothoraxes were seen at the outpatient clinic of the department of Clinical Genetics. Based on family history and physical examination, a suspicion of an underlying hereditary disorder arose. Birt-Hogg-Dubé syndrome and vascular Ehlers-Danlos syndrome were diagnosed through DNA-testing. Based on this, additional screening advices were given and DNA-testing became possible in the family. CONCLUSION: A spontaneous pneumothorax may be a manifestation of an underlying hereditary disorder. With attention to clinical symptoms and family history, physicians can contribute to timely diagnosis. In many cases this results in significant health benefits for both the patient and affected family members, such as screening for kidney cancer in the case of Birt-Hogg-Dubé syndrome.

A prospective, multicenter head-to-head comparative study in patients with primary high-risk prostate cancer investigating the bone lesion detection of conventional imaging and 18F-PSMA-PET/CT.

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is an emerging staging tool for patients with primary high-risk prostate cancer (PCa). Patients with primary metastatic disease are staged using PSMA-PET/CT imaging, while previously published randomized clinical trials relied on conventional imaging (i.e., bone scintigraphy (BS) results. The aim of this study was to compare the ability of bone metastatic lesion detection and changes in staging for 18F-PSMA-PET/CT versus BS in high-risk PCa patients. METHODS: 79 patients with high-risk PCa were prospectively staged using BS and subsequent 18F-PSMA-PET/CT before initial therapy. Patients who presented with a BS showing no metastases represented Group 1, and patients with a BS showing low-volume disease according to the CHAARTED criteria (<4 bone metastases, no metastases outside vertebral column or pelvis and no visceral metastases) represented Group 2. Metastatic risk group according to CHAARTED and treatment strategies based on both imaging modalities were assessed. RESULTS: A change of CHAARTED risk group was observed in 9/70 (12.8%) of patients in Group 1. In Group 2, a change of risk group was found in 66.7% of patients, due to either upstaging (4/9 patients (44.4%)) and downstaging (2/9 patients (22.2%)). Treatment changes due to use of a different imaging modality occurred in almost 20% of patients. CONCLUSION: In patients with negative for cancer results on BS, upstaging on 18F-PSMA-PET/CT occurred only infrequently. Moreover, 18F-PSMA-PET/CT resulted in both upstaging and downstaging in a substantial subset of patients with low-volume metastatic disease on BS. Treatment changes occurred in almost 20% of cases depending on imaging results.

Androgen Deprivation therapy for Oligo-recurrent Prostate cancer in addition to radioTherapy (ADOPT): study protocol for a randomised phase III trial.

BACKGROUND: More than 60% of oligo-recurrent prostate cancer (PCa) patients treated with metastasis-directed radiotherapy (MDRT) develop biochemical recurrence within 2 years. This recurrence rate emphasises the need for improved treatment and patient selection. In line with the treatment of primary PCa, the efficacy of MDRT may be enhanced when combined with androgen-deprivation therapy (ADT). Furthermore, the availability of PSMA PET/CT offers an excellent tool for optimal patient selection for MDRT. This phase III randomised controlled trial will investigate the role of the addition of ADT to MDRT in oligo-recurrent PCa patients selected with PSMA PET/CT to enhance oncological outcome. METHODS: Two hundred and eighty patients will be randomised in a 1:1 ratio to the standard treatment arm (MDRT alone) or the experimental arm (MDRT + 6 months ADT). Patients with biochemical recurrence after primary treatment of PCa presenting with ≤ 4 metastases will be included. The primary endpoint is the 2.5-year metastases progression-free survival (MPFS). Secondary endpoints are acute and late toxicity, quality of life, biochemical progression-free survival, overall survival, and the sensitivity of the PSMA PET/CT for detecting oligometastases at low PSA-levels. So far, between March 2020 and December 2021, one hundred patients have been included. DISCUSSION: This phase III randomised controlled trial will assess the possible benefit of the addition of 6 months ADT to MDRT on metastases progression-free survival, toxicity, QoL and survival in PCa patients with 1-4 recurrent oligometastatic lesions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04302454 . Registered 10 March 2020.

Functional outcomes rather than complications predict poor health-related quality of life at 6 months after robot-assisted radical prostatectomy.

The objective is to evaluate the effect of robot-assisted radical prostatectomy (RARP)-related postoperative complications on the 6-month postoperative health-related quality of life (HRQoL). A total of 1008 patients underwent a RARP with or without pelvic lymph node dissection (PLND) between 2012 and 2020 and were invited to complete questionnaires about HRQoL and functional outcomes (urinary incontinence (UI), erectile dysfunction (ED) and urinary complaints (UC)) before and 6 months after RARP. Patient characteristics and postoperative complications up to 90 days after surgery were prospectively recorded. Associations between complications and HRQoL/functional outcomes were assessed by multivariate linear regression analyses. In total, 528 patients (52.4%) were included in the analyses. Complications occurred in 165/528 (31.3%) patients, of which 30/165 (18.2%) had a Clavien-Dindo ≥ III complication. In multivariate regression analyses, postoperative complications were not significantly associated with postoperative HRQoL, UI and ED (p = 0.73, p = 0.72 and p = 0.95, respectively), but were significantly associated with a minor increase in UC (ß = 1.7, p < 0.001). More specifically, infectious and urological complications were significantly associated with an increase in UC (ß = 1.9, p < 0.001 and ß = 0.9, p = 0.004, respectively). The presence of UTI, in particular, was significantly associated with this minor increase (ß = 1.5, p = 0.002). Functional outcomes were all significantly associated with the HRQoL at 6 months postoperatively. No significant associations were found between postoperative complications and HRQoL at 6 months after RARP. However, worse functional outcomes were associated with a worse HRQoL at 6 months postoperatively. In addition, postoperative infectious and urological complications were significantly associated with a minor increase in UC.

The effects of new life-prolonging drugs for metastatic castration-resistant prostate cancer (mCRPC) patients in a real-world population.

BACKGROUND: In 2004 docetaxel was the first life-prolonging drug (LPD) registered for metastatic castration-resistant prostate cancer (mCRPC) patients. Between 2011 and 2014 new LPDs for mCRPC (cabazitaxel, abiraterone, enzalutamide, and radium-223) were introduced in the Netherlands. The objective of this study is to assess the impact of the introduction of new LPDs on treatment patterns and overall survival (OS) over time. PATIENTS AND METHODS: CRPC patients diagnosed in the years 2010-2016 in the observational, retrospective CAPRI registry (20 hospitals) were included and followed up to 2018. Two subgroups were analyzed: treatment-naïve patients (subgroup 1, n = 3600) and post-docetaxel patients (subgroup 2, n = 1355). RESULTS: In both subgroups, the use of any LPD increased: from 57% (2010-2011) to 69% (2014-2015) in subgroup 1 and from 65% (2011-2012) to 79% (2015-2016) in subgroup 2. Chemotherapy as first mCRPC-treatment (i.e., docetaxel) and first post-docetaxel treatment (i.e., cabazitaxel or docetaxel rechallenge) decreased (46-29% and 20-9% in subgroup 1 and 2, respectively), while the use of androgen-receptor targeting treatments (ART) increased from 11% to 39% and 46% to 64% in subgroup 1 and 2, respectively. In subgroup 1, median OS (mOS) from diagnosis CRPC increased from 28.5 months to 31.0 months (p = 0.196). In subgroup 2, mOS from progression on docetaxel increased from 7.9 months to 12.5 months (p < 0.001). After multiple imputations of missing values, in multivariable cox-regression analysis with known prognostic parameters, the treatment period was independent significant for OS in subgroup 1 (2014-2015 vs. 2010-2011 with HR 0.749, p < 0.001) and subgroup 2 (2015-2016 vs. 2011-2012 with HR 0.811, p = 0.037). CONCLUSION: Since 2010, a larger proportion of mCRPC patients was treated with LPDs, which was related to an increased mOS.

Detection of prostate cancer with 18F-DCFPyL PET/CT compared to final histopathology of radical prostatectomy specimens: is PSMA-targeted biopsy feasible? The DeTeCT trial.

PURPOSE: In primary prostate cancer (PCa) patients, accurate staging and histologic grading are crucial to guide treatment decisions. 18F-DCFPyL (PSMA)-PET/CT has been successfully introduced for (re)staging PCa, showing high accuracy to localise PCa in lymph nodes and/or osseous structures. The diagnostic performance of 18F-DCFPyL-PET/CT in localizing primary PCa within the prostate gland was assessed, allowing for PSMA-guided targeted-prostate biopsy. METHODS: Thirty patients with intermediate-/high-risk primary PCa were prospectively enrolled between May 2018 and May 2019 and underwent 18F-DCFPyL-PET/CT prior to robot-assisted radical prostatectomy (RARP). Two experienced and blinded nuclear medicine physicians assessed tumour localisation within the prostate gland on PET/CT, using a 12-segment mapping model of the prostate. The same model was used by a uro-pathologist for the RARP specimens. Based on PET/CT imaging, a potential biopsy recommendation was given per patient, based on the size and PET-intensity of the suspected PCa localisations. The biopsy recommendation was correlated to final histopathology in the RARP specimen. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for clinically significant PCa (csPCa, Gleason score ≥ 3 + 4 = 7) were assessed. RESULTS: The segments recommended for potential targeted biopsy harboured csPCA in 28/30 patients (93%), and covered the highest Gleason score PCa segment in 26/30 patient (87%). Overall, 122 of 420 segments (29.0%) contained csPCa at final histopathological examination. Sensitivity, specificity, PPV and NPV for csPCa per segment using 18F-DCFPyL-PET/CT were 61.4%, 88.3%, 68.1% and 84.8%, respectively. CONCLUSIONS: When comparing the PCa-localisation on 18F-DCFPyL-PET/CT with the RARP specimens, an accurate per-patient detection (93%) and localisation of csPCa was found. Thus, 18F-DCFPyL-PET/CT potentially allows for accurate PSMA-targeted biopsy.

Pelvic lymph-node staging with 18F-DCFPyL PET/CT prior to extended pelvic lymph-node dissection in primary prostate cancer - the SALT trial.

PURPOSE: The detection of lymph-node metastases (N1) with conventional imaging such as magnetic resonance imaging (MRI) and computed tomography (CT) is inadequate for primarily diagnosed prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) PET/CT is successfully introduced for the staging of (biochemically) recurrent PCa. Besides the frequently used 68gallium-labelled PSMA tracers, 18fluorine-labelled PSMA tracers are available. This study examined the diagnostic accuracy of 18F-DCFPyL (PSMA) PET/CT for lymph-node staging in primary PCa. METHODS: This was a prospective, multicentre cohort study. Patients with primary PCa underwent 18F-DCFPyL PET/CT prior to robot-assisted radical prostatectomy (RARP) with extended pelvic lymph-node dissection (ePLND). Patients were included between October 2017 and January 2020. A Memorial Sloan Kettering Cancer Centre (MSKCC) nomogram risk probability of ≥ 8% of lymph-node metastases was set to perform ePLND. All images were reviewed by two experienced nuclear physicians, and were compared with post-operative histopathologic results. RESULTS: A total of 117 patients was analysed. Lymph-node metastases (N1) were histologically diagnosed in 17/117 patients (14.5%). The sensitivity, specificity, positive predictive value and negative predictive value for the 18F-DCFPyL PET/CT detection of pelvic lymph-node metastases on a patient level were 41.2% (confidence interval (CI): 19.4-66.5%), 94.0% (CI 86.9-97.5%), 53.8% (CI 26.1-79.6%) and 90.4% (CI 82.6-95.0%), respectively. CONCLUSION: 18F-DCFPyL PET/CT showed a high specificity (94.4%), yet a limited sensitivity (41.2%) for the detection of pelvic lymph-node metastases in primary PCa. This implies that current PSMA PET/CT imaging cannot replace diagnostic ePLND. Further research is necessary to define the exact place of PSMA PET/CT imaging in the primary staging of PCa.

Urinary incontinence and erectile dysfunction in patients with localized or locally advanced prostate cancer: A nationwide observational study.

BACKGROUND: Although urinary adverse events after treatment of prostate cancer (CaP) are common, population-based studies on functional outcomes are scarce. The aim of this study is to evaluate the occurrence of urinary incontinence (UI) and erectile dysfunction (ED) in daily clinical practice using a nationwide Dutch cohort of patients with localized or locally advanced CaP. BASIC PROCEDURES: Patients were invited to complete the EPIC-26 questionnaire before treatment (baseline) and at 12 and 24 months after diagnosis. We calculated the mean EPIC-26 domain scores, stratified by treatment modality (i.e., radical prostatectomy, external radiotherapy, and no active treatment), and the proportions of patients with UI (defined as ≥ 2 pads per day) and ED (defined as erections not firm enough for sexual intercourse). Logistic regression modeling was used to explore the factors related to UI and ED after surgery. MAIN FINDINGS: In total 1,759 patients participated in this study. Patients undergoing radical prostatectomy experienced clinically relevant worsening in the urinary incontinence domain. After excluding patients who reported UI at baseline, 15% of patients with prostatectomy reported UI 24 months after diagnosis. Only comorbidity was associated with UI in surgically treated patients. Regardless of treatment, patients reported a clinically significant reduced sexual functioning over time. Before treatment, 54% of patients reported ED. Among the 46% remaining patients, 87% of patients treated with radical prostatectomy reported ED 24 months after diagnosis, 41% after radiotherapy, and 46% in patients without active treatment. Bilateral nerve-sparing surgery was the only factor associated with ED after 24 months. PRINCIPAL CONCLUSIONS: UI and ED frequently occur in patients with localized and locally advanced CaP, in particular after radical prostatectomy. The higher occurrence rate of UI and ED, compared with clinical trial participants, supports the importance of real-world data, which can be used for local treatment recommendations and patient information, but also to evaluate effects of future initiatives, such as treatment centralization and research aimed at improving functional outcomes.

Correction to: Letter to the Editor re: Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Impact of Tumor Burden on Normal Organ Uptake.

The article was updated to correct the following errors due to an error in production.

Sexual Dysfunction and Bother Due to Erectile Dysfunction in the Healthy Elderly Male Population: Prevalence from a Systematic Review.

CONTEXT: Therapies initiated by urologists, medical as well as surgical, may cause adverse effects in different sexual domains. Sexual domains that are often affected are sexual interest, sexual activity, and erectile functioning. As many elderly men undergo these therapies, it is important to know the prevalence of sexual dysfunction (SD) in these domains and its impact in the healthy elderly male population. This may help healthcare providers counsel their patients properly on possible adverse effects. OBJECTIVE: To review the prevalence of sexual functioning and SD in the domains of sexual desire, sexual activity, and erectile dysfunction (ED) and its impact (bother and medical use), stratified by age. EVIDENCE ACQUISITION: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Studies investigating the prevalence of SD, stratified by age, were eligible. Studies investigating bother due to ED, and studies evaluating medical use or use of medical professional healthcare providers in association with SD were eligible. EVIDENCE SYNTHESIS: A total of 76 articles were eligible for a full systematic review. Lack of sexual desire was reported to vary between 12% and 51.6% for men aged ≥60 yr, 20% and 65.9% for men aged ≥70 yr, and 40% and 82.4% for men aged ≥80 yr. The percentages of men bothered by ED were as follows: 14.3-70% for men aged ≥60 yr, 6.7-48% for men aged ≥70 yr, and 38% for men aged ≥80 yr. A substantial number of men (50.3-92%) find a normal sex life important as they age and remain sexually active. Only a minority of elderly men seek help from healthcare professionals or use medication for SD. CONCLUSIONS: The prevalence of SD in the healthy male population, reflected by a loss of sexual desire and sexual activity, increases only slightly with age. Bother due to ED is relatively low and there is an association with age. Still, a large number of men in the middle-aged and elderly groups regard sexuality as an important aspect of life. While considering a surgical or medical therapy that could have an impact on sexual functioning, sexually related outcomes should be set against current sexual functioning and a probable decline of sexual functioning due to ageing. PATIENT SUMMARY: While counselling elderly patients for sexual dysfunction when starting a treatment that could have an influence on sexual functioning, one should consider current sexual functioning and its importance for the individual.

Early lesion detection with 18F-DCFPyL PET/CT in 248 patients with biochemically recurrent prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemically recurrent prostate cancer (BCR), mostly using gallium-68 (168Ga)-labelled radiotracers. Alternatively, fluorine-18 (18F)-labelled PSMA tracers are available, such as 18F-DCFPyL, which offer enhanced image quality and therefore potentially increased detection of small metastases. In this study we evaluate the lesion detection efficacy of 18F-DCFPyL PET/CT in patients with BCR and determine the detection efficacy as a function of their PSA value. METHODS: A total of 248 consecutive patients were evaluated and underwent scanning with 18F-DCFPyL PET/CT for BCR between November 2016 and 2018 in two hospitals in the Netherlands. Patients were examined after radical prostatectomy (52%), external-beam radiation therapy (42%) or brachytherapy (6%). Imaging was performed 120 min after injection of a median dose of 311 MBq 18F-DCFPyL. RESULTS: In 214 out of 248 PET/CT scans (86.3%), at least one lesion suggestive of cancer recurrence was detected ('positive scan'). Scan positivity increased with higher PSA values: 17/29 scans (59%) with PSA values <0.5 ng/ml; 20/29 (69%) with PSA 0.5 to <1.0 ng/ml; 35/41 (85%) with PSA 1.0 to <2.0 ng/ml; 69/73 (95%) with PSA 2.0 to <5.0 ng/ml; and 73/76 (96%) with PSA ≥5.0 ng/ml. Interestingly, suspicious lesions outside the prostatic fossa were detected in 39-50% of patients with PSA <1.0 ng/ml after radical prostatectomy (i.e. candidates for salvage radiotherapy). CONCLUSION: 18F-DCFPyL PET/CT offers early detection of lesions in patients with BCR, even at PSA levels <0.5 ng/ml. These results appear to be comparable to those reported for 68Ga-PSMA and 18F-PSMA-1007, with potentially increased detection efficacy compared to 68Ga-PSMA for patients with PSA <2.0.

[Androgen receptor inhibitors in prostate cancer: new drugs, but for which patient?] / Androgeenreceptorremming tegen prostaatkanker: nieuwe middelen, maar voor welke patiënt?

The results of a recent randomised phase 3 clinical trial show that the androgen receptor antagonist darolutamide improves metastasis-free survival in men with non-metastatic, castration-resistant prostate cancer, compared with placebo. The trial included 1509 men with a prostate-specific antigen doubling time of 10 months or less. Non-metastatic disease was defined as the absence of metastases, using conventional imaging rather than the substantially more sensitive PSMA scans. The effect of darolutamide is similar to that of other androgen inhibitors, such as apalutamide and enzalutamide. The value of the current trial to Dutch clinical practice is limited, as the number of patients with non-metastatic, castration-resistant prostate cancer is low due to the increased use of PSMA scans and the reluctance of urologists to start androgen-deprivation therapy in the absence of metastatic disease.

A protocol for urine collection and storage prior to DNA methylation analysis.

BACKGROUND: Urine poses an attractive non-invasive means for obtaining liquid biopsies for oncological diagnostics. Especially molecular analysis on urinary DNA is a rapid growing field. However, optimal and practical storage conditions that result in preservation of urinary DNA, and in particular hypermethylated DNA (hmDNA), are yet to be determined. AIM: To determine the most optimal and practical conditions for urine storage that result in adequate preservation of DNA for hmDNA analysis. METHODS: DNA yield for use in methylation analysis was determined by quantitative methylation specific PCR (qMSP) targeting the ACTB and RASSF1A genes on bisulfite modified DNA. First, DNA yield (ACTB qMSP) was determined in a pilot study on urine samples of healthy volunteers using two preservatives (Ethylenediaminetetraacetic acid (EDTA) and Urine Conditioning Buffer, Zymo Research) at four different temperatures (room temperature (RT), 4°C, -20°C, -80°C) for four time periods (1, 2, 7, 28 days). Next, hmDNA levels (RASSF1A qMSP) in stored urine samples of patients suffering from bladder cancer (n = 10) or non-small cell lung cancer (NSCLC; n = 10) were measured at day 0 and 7 upon storage with and without the addition of 40mM EDTA and/or 20 µl/ml Penicillin Streptomycin (PenStrep) at RT and 4°C. RESULTS: In the pilot study, DNA for methylation analysis was only maintained at RT upon addition of preserving agents. In urine stored at 4°C for a period of 7 days or more, the addition of either preserving agent yielded a slightly better preservation of DNA. When urine was stored at -20 °C or -80 °C for up to 28 days, DNA was retained irrespective of the addition of preserving agents. In bladder cancer and NSCLC samples stored at RT loss of DNA was significantly less if EDTA was added compared to no preserving agents (p<0.001). Addition of PenStrep did not affect DNA preservation (p>0.99). Upon storage at 4°C, no difference in DNA preservation was found after the addition of preserving agents (p = 0.18). The preservation of methylated DNA (RASSF1A) was strongly correlated to that of unmethylated DNA (ACTB) in most cases, except when PCR values became inaccurate. CONCLUSIONS: Addition of EDTA offers an inexpensive preserving agent for urine storage at RT up to seven days allowing for reliable hmDNA analysis. To avoid bacterial overgrowth PenStrep can be added without negatively affecting DNA preservation.

Case Presentation: Botox Versus Nerve Stimulation.

A woman experiencing very strong urgency and associated frequency of micturition, but no incontinence, and deep dyspareunia was eventually diagnosed with idiopathic detrusor overactivity with symptoms of overactive bladder symptom complex and potentially bladder pain syndrome. A trial of neuromodulation was unsuccessful, but injections of onabotulinum toxin A have had a good effect.

Customized Tool for the Validation of Optical Coherence Tomography in Differentiation of Prostate Cancer.

OBJECTIVE: To design and demonstrate a customized tool to generate histologic sections of the prostate that directly correlate with needle-based optical coherence tomography pullback measurements. MATERIALS AND METHODS: A customized tool was created to hold the prostatectomy specimens during optical coherence tomography measurements and formalin fixation. Using the tool, the prostate could be sliced into slices of 4 mm thickness through the optical coherence tomography measurement trajectory. In this way, whole-mount pathology slides were produced in exactly the same location as the optical coherence tomography measurements were performed. Full 3-dimensional optical coherence tomography pullbacks were fused with the histopathology slides using the 3-dimensional imaging software AMIRA, and images were compared. RESULTS: A radical prostatectomy was performed in a patient (age: 68 years, prostate-specific antigen: 6.0 ng/mL) with Gleason score 3 + 4 = 7 in 2/5 biopsy cores on the left side (15%) and Gleason score 3 + 4 = 7 in 1/5 biopsy cores on the right side (5%). Histopathology after radical prostatectomy showed an anterior located pT2cNx adenocarcinoma (Gleason score 3 + 4 = 7). Histopathological prostate slides were produced using the customized tool for optical coherence tomography measurements, fixation, and slicing of the prostate specimens. These slides correlated exactly with the optical coherence tomography images. Various structures, for example, Gleason 3 + 4 prostate cancer, stroma, healthy glands, and cystic atrophy with septae, could be identified both on optical coherence tomography and on the histopathological prostate slides. CONCLUSION: We successfully designed and applied a customized tool to process radical prostatectomy specimens to improve the coregistration of whole mount histology sections to fresh tissue optical coherence tomography pullback measurements. This technique will be crucial in validating the results of optical coherence tomography imaging studies with histology and can easily be applied in other solid tissues as well, for example, lung, kidney, breast, and liver. This will help improve the efficacy of optical coherence tomography in cancer detection and staging in solid organs.

Vimentin over-expression and carbonic anhydrase IX under-expression are independent predictors of recurrence, specific and overall survival in non-metastatic clear-cell renal carcinoma: a validation study.

PURPOSE: Clinical outcomes prognostic markers are awaited in clear-cell renal carcinoma (ccRCC) to improve patient-tailored management and to assess six different markers' influence on clinical outcomes from ccRCC specimen and their incremental value combined with TNM staging. MATERIALS AND METHODS: This is a retrospective, multicenter study. One hundred and forty-three patients with pT1b-pT3N0M0 ccRCC were included. Pathology specimens from surgeries were centrally reviewed, mounted on a tissue micro-array and stained with six markers: CAIX, c-MYC, Ki67, p53, vimentin and PTEN. Images were captured through an Ultra Fast Scanner. Tumor expression was measured with Image Pro Plus. Cytoplasmic markers (PTEN, CAIX, vimentin, c-MYC) were expressed as surface percentage of expression. Nuclear markers (Ki67, p53) were expressed as number of cells/mm2. Clinical data and markers expression were compared with clinical outcomes. Each variable was included in the Cox proportional multivariate analyses if p < 0.10 on univariate analyses. Discrimination of the new marker was calculated with Harrell's concordance index. RESULTS: At median follow-up of 63 months (IQR 35.0-91.8), on multivariate analysis, CAIX under-expression and vimentin over-expression were associated with worse survival (recurrence, specific and overall survival). A categorical marker CAIX-/Vimentin+ with cutoff points for CAIX and vimentin of 30 and 50 %, respectively, was designed. The new CAIX-/Vimentin+ marker presented a good concordance and comparable calibration to the reference model. Limitations are the retrospective design, the need for external validation and the large study period. CONCLUSION: Using an automated technique of measurement, CAIX and vimentin are independent predictors of clinical outcomes in ccRCC.