A risk calculator to inform the need for a prostate biopsy: a rapid access clinic cohort.

BACKGROUND: Prostate cancer (PCa) represents a significant healthcare problem. The critical clinical question is the need for a biopsy. Accurate risk stratification of patients before a biopsy can allow for individualised risk stratification thus improving clinical decision making. This study aims to build a risk calculator to inform the need for a prostate biopsy. METHODS: Using the clinical information of 4801 patients an Irish Prostate Cancer Risk Calculator (IPRC) for diagnosis of PCa and high grade (Gleason ≥7) was created using a binary regression model including age, digital rectal examination, family history of PCa, negative prior biopsy and Prostate-specific antigen (PSA) level as risk factors. The discrimination ability of the risk calculator is internally validated using cross validation to reduce overfitting, and its performance compared with PSA and the American risk calculator (PCPT), Prostate Biopsy Collaborative Group (PBCG) and European risk calculator (ERSPC) using various performance outcome summaries. In a subgroup of 2970 patients, prostate volume was included. Separate risk calculators including the prostate volume (IPRCv) for the diagnosis of PCa (and high-grade PCa) was created. RESULTS: IPRC area under the curve (AUC) for the prediction of PCa and high-grade PCa was 0.6741 (95% CI, 0.6591 to 0.6890) and 0.7214 (95% CI, 0.7018 to 0.7409) respectively. This significantly outperforms the predictive ability of cancer detection for PSA (0.5948), PCPT (0.6304), PBCG (0.6528) and ERSPC (0.6502) risk calculators; and also, for detecting high-grade cancer for PSA (0.6623) and PCPT (0.6804) but there was no significant improvement for PBCG (0.7185) and ERSPC (0.7140). The inclusion of prostate volume into the risk calculator significantly improved the AUC for cancer detection (AUC = 0.7298; 95% CI, 0.7119 to 0.7478), but not for high-grade cancer (AUC = 0.7256; 95% CI, 0.7017 to 0.7495). The risk calculator also demonstrated an increased net benefit on decision curve analysis. CONCLUSION: The risk calculator developed has advantages over prior risk stratification of prostate cancer patients before the biopsy. It will reduce the number of men requiring a biopsy and their exposure to its side effects. The interactive tools developed are beneficial to translate the risk calculator into practice and allows for clarity in the clinical recommendations.

A case report of mucinous tubular and spindle cell carcinoma of the kidney.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor that has only recently been described, with less than eighty cases in the literature. This was only recognized as a specific entity in the World Health Organization 2004 classification of Renal Cell Carcinoma (RCC). MTSCCs are polymorphic renal neoplasms characterized by small, elongated tubules lined by cuboidal cells with cords of spindled cells separated by pale mucinous stroma. We report the case of a 57 year old lady who had an incidental finding of a mass in her right kidney. The radiological features were consistent with a RCC and following a multidisciplinary team discussion she underwent a laparoscopic radical nephrectomy. Macroscopic examination revealed a well circumscribed 6.5 × 6 × 6.5 cm right lower pole mass. Histologically it was composed of elongated tubules, small tubules and papillary structures with a necrotic centre. The cells demonstrated cuboidal and spindle cell morphology. Histological grade was Fuhrman grade 2. The majority of MTSCCs are indolent, and there are only two reports of distant metastases which responded favorably to adjuvant sunitinib. To date there is no international consensus on long term surveillance of these patients. Due of the favorable prognosis with this type of tumor, MTSCC must be differentiated from papillary renal cell carcinoma to avoid administration of excessive adjuvant treatment to patients.

Outcomes from the Introduction of a Combined Urology Outpatient Clinic.

BACKGROUND: A combined urology clinic staffed by four consultants and four non-consultant hospital doctors (NCHDs) was introduced in our institution in October 2015. This clinic is supported by a pre-clinic radiology meeting and a synchronous urology clinical nurse specialist (CNS) clinic with protected uroflow/trial of void slots. Herein, we report on the outcomes of this clinic in comparison with the standard format of urology outpatient review. METHODS: We carried out a retrospective review of clinic attendances from May to July 2016. We recorded the number of new and return attendances, which team members had reviewed the patient and patient outcomes. We also calculated the waiting times for new patients to be reviewed in the outpatient clinic. RESULTS: The combined urology clinic reviewed an average of 12 new and 46 return patients per clinic. The standard urology clinic reviewed an average of 8 new and 23 return patients per clinic. 54% of patients were seen by a consultant in the combined urology clinic, and 20% of patients were seen by a consultant in the standard urology clinic. The rate of patient discharge for new patients was 14.8% in the combined clinic compared to 5.9% in the standard clinic. Overall patient outcomes are outlined in the table. The waiting time for review of new patients in the combined clinic was reduced by 39% from 144 days to 89 days over a one-year period. CONCLUSIONS: The introduction of a combined urology outpatient clinic with the support of pre-clinic radiology meeting and synchronous urology CNS clinic facilitates patient discharge.

Alteration in urinary matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio predicts recurrence in nonmuscle-invasive bladder cancer.

PURPOSE: The purpose is to assess the prognostic significance of matrix metalloproteinase (MMP)-9 in patients with bladder cancer using a combination of ELISA (to measure MMP-9 in voided urine) and immunohistochemistry (to study MMP-9 in bladder tumors). The relationship between MMP-9 and its principal inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 (in voided urine samples) was also studied. EXPERIMENTAL DESIGN: A total of 134 patients with bladder tumors (7 cis, 76 T(a), 27 T(1), 24 T(2)-T(4); 40 G1, 43 G2, and 44 G3), 33 patients with benign urological conditions, and 36 healthy volunteers was studied. Samples from 106 patients with bladder cancer and 12 controls were stained for MMP-9. Clinical follow-up data were available on 116 patients (median: 25 months; range: 4-36 months). RESULTS: MMP-9 was present in all urine samples analyzed. There were no differences between patients with cancer and patients with benign disorders. However, patients had significantly higher urinary MMP-9 than normal volunteers (P = 0.0167). Urinary MMP-9 was associated with bladder tumors of advanced stage (P = 0.0065) and large size (P < 0.0001) but not with grade (P = 0.14), multiplicity (P = 0.31), recurrence (P = 0.55), progression (P = 0.83), or survival (P = 0.55). Low MMP-9:TIMP-1 ratios in patients with nonmuscle-invasive tumors were associated with higher recurrence rates (P = 0.0035). Sixty percent (64 of 106) of bladder tumor specimens expressed MMP-9 compared with none of 12 normal urothelial biopsies (P < 0.0001). MMP-9 staining was associated with tumor size (P = 0.014), disease progression (P = 0.005), and poor disease-specific survival (P = 0.022) but was unrelated to tumor stage (P = 0.46), grade (P = 0.26), multiplicity (P = 0.85), or recurrence rate (P = 0.62). CONCLUSIONS: High urinary MMP-9 levels are associated with large bladder tumors. A low urinary MMP-9:TIMP-1 ratio may indicate a higher risk of intraluminal nonmuscle-invasive tumor recurrence and may assist in planning follow-up surveillance protocols.

A Circulating MicroRNA Signature as a Biomarker for Prostate Cancer in a High Risk Group.

INTRODUCTION: Mi(cro)RNAs are small non-coding RNAs whose differential expression in tissue has been implicated in the development and progression of many malignancies, including prostate cancer. The discovery of miRNAs in the blood of patients with a variety of malignancies makes them an ideal, novel biomarker for prostate cancer diagnosis. The aim of this study was to identify a unique expression profile of circulating miRNAs in patients with prostate cancer attending a rapid access prostate assessment clinic. METHODS: To conduct this study blood and tissue samples were collected from 102 patients (75 with biopsy confirmed cancer and 27 benign samples) following ethical approval and informed consent. These patients were attending a prostate assessment clinic. Samples were reverse-transcribed using stem-loop primers and expression levels of each of 12 candidate miRNAs were determined using real-time quantitative polymerase chain reaction. miRNA expression levels were then correlated with clinicopathological data and subsequently analysed using qBasePlus software and Minitab. RESULTS: Circulating miRNAs were detected and quantified in all subjects. The analysis of miRNA mean expression levels revealed that four miRNAs were significantly dysregulated, including let-7a (p = 0.005) which has known tumour suppressor characteristics, along with miR-141 (p = 0.01) which has oncogenic characteristics. In 20 patients undergoing a radical retropubic-prostatectomy, the expression levels of miR-141 returned to normal at day 10 post-operatively. A panel of four miRNAs could be used in combination to detect prostate cancer with an area under the curve (AUC) of 0.783 and a PPV of 80%. CONCLUSION: These findings identify a unique expression profile of miRNA detectable in the blood of prostate cancer patients. This confirms their use as a novel, diagnostic biomarker for prostate cancer.

Developing a laparoscopic radical prostatectomy service: defining the learning curve.

BACKGROUND AND PURPOSE: Laparoscopic radical prostatectomy (LRP) is an established treatment for patients with prostate cancer in selected centers with appropriate expertise. We studied our single-center experience of developing a LRP service and subsequent training of two additional surgeons by the initial surgeon. We assessed the learning curve of the three surgeons with regard to perioperative outcomes and oncologic results. PATIENTS AND METHODS: Three hundred consecutive patients underwent a LRP between January 2005 and April 2011. Patients were divided into three equal groups (1-100 group 1], 101-200 [group 2], and 201-300 [group 3]). Age, American Society of Anesthesiologists score, preoperative comorbidities, and indications for LRP were comparable for all three patient groups. Perioperative and oncologic outcomes were compared across all three groups to assess the impact of the learning curve for LRP. All surgical complications were classified using the Clavien-Dindo system (CDS). RESULTS: The mean age was 61.9 years (range 46-74 y). There was a significant reduction in the mean operative time (P<0.05), mean blood loss (P<0.05), mean duration of hospital stay (P<0.05), and duration of catherization (P<0.05) between the three groups as the series progressed. The two most important factors predictive of positive surgical margins at LRP were the initial prostate-specific antigen level and tumor stage at diagnosis. The overall positive margin rate was 27.7%. For pT(2) tumors, the positive margin rate was 21%, while patients with pT(3) tumors had a positive margin of 44%. For pT(2) tumors, positive margin rates decreased with increasing experience (group 1, 27% vs group 2, 17% vs group 3, 19%). The incidence of major complications--ie, grade CDS score ≤ III--was 4.6% (14/300). CONCLUSION: LRP is a safe procedure with low morbidity. As surgeons progress through the learning curve, perioperative parameters and oncologic outcomes improve. Using a carefully mentored approach, LRP can be safely introduced as a new procedure without compromising patient outcomes.

The impact of early re-resection in patients with pT1 high-grade non-muscle invasive bladder cancer.

AIM: To evaluate the impact of early re-resection on the incidence of tumour recurrence and progression in patients with pT1 high-grade non-muscle invasive bladder cancer (HG-NMIBC). PATIENTS AND METHODS: From 2001 to 2008, 486 consecutive patients were diagnosed with pT1 HG-NMIBC. Data were collected retrospectively which included patient demographics, histological parameters including the presence of detrusor muscle at initial TUR and at re-resection, adjuvant intravesical therapy, and recurrence and progression rates. Early re-resection was performed within six weeks of initial TUR. Patients comprised those who underwent an early re-resection (Group A, n = 172) and those who did not (Group B, n = 314). RESULTS: At initial TUR, detrusor muscle was present in 61% (n = 105) of patients in Group A and 76% (n = 240) of patients in Group B. At early re-resection, detrusor muscle was present in 77.9% of cases. A residual tumour was present in 54.6% of re-resected cases. The overall incidence of tumour recurrence was 35% and 42% in Groups A and B, respectively. During follow-up, there was a significantly higher rate of tumour stage progression in patients who did not undergo early re-resection (Group B 14.4% vs. Group A 3.3%, P < 0.05). CONCLUSIONS: Early re-resection facilitates accurate staging and clearance of residual disease. Subsequent rates of tumour stage progression are significantly improved. We advocate early re-resection for all patients with HG-NMIBC.

Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer.

The calcium-binding protein S100A4 induces the metastatic phenotype in rodent models of breast cancer and its expression correlates strongly with reduced survival in human breast cancer. The expression of S100A4 in normal bladders and 101 bladder tumours has been studied using immunocytochemistry. Moderate or strong expression of S100A4 was found in 28% of the tumours, whilst the remaining tumours and normal urothelium either failed to stain or showed weak staining. S100A4 staining was more frequently observed in invasive bladder tumours than in non-invasive tumours (p<0.05). In invasive tumours, S100A4 staining was usually strongest in invasive regions and single infiltrating cells. Statistically significant associations were found between S100A4 expression and metastasis (p=0.0003) and reduced survival (p<0.0001). It is concluded that S100A4 expression may play an important role in bladder cancer and may identify a subgroup of patients at increased risk of metastasis who should be considered for adjuvant systemic therapy.