Metabolomic Prediction of Human Prostate Cancer Aggressiveness: Magnetic Resonance Spectroscopy of Histologically Benign Tissue.

Prostate cancer alters cellular metabolism through events potentially preceding cancer morphological formation. Magnetic resonance spectroscopy (MRS)-based metabolomics of histologically-benign tissues from cancerous prostates can predict disease aggressiveness, offering clinically-translatable prognostic information. This retrospective study of 185 patients (2002-2009) included prostate tissues from prostatectomies (n = 365), benign prostatic hyperplasia (BPH) (n = 15), and biopsy cores from cancer-negative patients (n = 14). Tissues were measured with high resolution magic angle spinning (HRMAS) MRS, followed by quantitative histology using the Prognostic Grade Group (PGG) system. Metabolic profiles, measured solely from 338 of 365 histologically-benign tissues from cancerous prostates and divided into training-testing cohorts, could identify tumor grade and stage, and predict recurrence. Specifically, metabolic profiles: (1) show elevated myo-inositol, an endogenous tumor suppressor and potential mechanistic therapy target, in patients with highly-aggressive cancer, (2) identify a patient sub-group with less aggressive prostate cancer to avoid overtreatment if analysed at biopsy; and (3) subdivide the clinicopathologically indivisible PGG2 group into two distinct Kaplan-Meier recurrence groups, thereby identifying patients more at-risk for recurrence. Such findings, achievable by biopsy or prostatectomy tissue measurement, could inform treatment strategies. Metabolomics information can help transform a morphology-based diagnostic system by invoking cancer biology to improve evaluation of histologically-benign tissues in cancer environments.

Active surveillance for low-risk prostate cancer: Need for intervention and survival at 10 years.

INTRODUCTION: To describe the need for treatment and cancer-specific and overall survival in a contemporary active surveillance (AS) cohort. PATIENTS AND METHODS: Historical cohort study of men diagnosed with localized prostate cancer between 1997 and 2009 and managed with AS at a tertiary care center. Inclusion criteria were Gleason score ≤ 6 (Gleason score of 7 in select patients),≤ 3/12 cores positive, and prostate-specific antigen (PSA) level< 20 ng/ml. Survival analyses were conducted using the Kaplan-Meier method. RESULTS: A total of 469 men with median age at diagnosis of 68.1 years (interquartile range [IQR]: 62.5-73.4) were followed up for a median of 4.8 years (IQR: 3.4-7.3). Median PSA level at diagnosis was 5.1 ng/ml (IQR: 4.0-6.9), with 94% of them having PSA level<10 ng/ml. Overall, 98.3% (461/469) of patients had a Gleason score of 6 and 1.7% (8/469) had a Gleason score of 3+4 = 7, and 94.0% (441/469) had T1c stage disease. Freedom from treatment was 77% at 5 years and 62% at 10 years. A total of 116 (24.7%) patients received treatment during the course of surveillance. Reasons for treatment included 44.8% (52/116) for pathologic reclassification, 30.2% (35/116) for PSA progression, 12.1% (14/116) for patient preference, 5.2% (6/116) for digital rectal examination progression, and 4.3% (5/116) for metastatic disease. Of the patients treated, 59 (50.1%) received radiation, 26 (22.4%) underwent surgery, 17 (14.7%) received brachytherapy, and 14 (12.1%) received androgen-deprivation therapy. Cancer-specific survival was 100% at 5 and 10 years. Overall survival was 95% at 5 years and 88% at 10 years. CONCLUSION: In a contemporary cohort of men with low-risk prostate cancer, AS allowed avoidance of treatment most of them. Common reasons for change in management were Gleason upgrading and volume progression on prostate rebiopsy.

Long-term outcomes of organ preservation in patients with small cell carcinoma of the bladder.

BACKGROUND: Small cell carcinoma of the bladder is an uncommon but clinically aggressive disease. There is no standard surgical or medical management for the disease. METHODS: Between 1995 and 2009, 28 patients underwent transurethral resection (TUR) and/or cystectomy, chemotherapy, and/or radiation for small cell carcinoma of the bladder at our institution. RESULTS: The median follow-up for survivors was 34 months. Patients presented most often with muscle-invasive disease (T2-4 - 89%), and 21% had lymph node/distant metastases. Tobacco use and chemical exposure were noted in 64 and 4% of patients, respectively. Patients with T1-2N0M0 had a median survival of 22 months compared to 8 months for those with more advanced disease (p = 0.03). Patients with T3-4 or nodal/metastatic disease who were given chemotherapy had an improved survival compared to those with T3-4 or nodal/metastatic disease who did not undergo chemotherapy (13 vs. 4 months, p = 0.005). The median time to recurrence of the entire cohort was 8 months, overall and cancer-specific survival was 14 months, and 5-year survival was 11%. CONCLUSIONS: Small cell carcinoma of the bladder is an aggressive disease with poor outcomes. Patients with T1-2N0M0 disease survived longer than those with advanced disease. Patients with T3-4 or nodal/metastatic disease had improved survival with chemotherapy.

Mucosa-sparing, KTP laser coagulation of submucosal telangiectatic vessels in patients with radiation-induced cystitis: a novel approach.

INTRODUCTION: This study aimed evaluate the safety and feasibility of endoscopic potassium titanyl phosphate (KTP) laser application in the management of patients with radiation-induced hemorrhagic cystitis (RHC). TECHNICAL CONSIDERATIONS: We retrospectively reviewed the records of 20 patients with RHC who underwent endoscopic KTP laser ablation of telangiectatic bladder vessels between October 2005 and January 2013. After initial cystoscopy, KTP laser was used to ablate the submucosal vasculature while preserving the overlying mucosa. The surgical outcome was evaluated by duration of hematuria-free interval, number of episodes of hematuria, and number of required medical and/or surgical interventions after initial treatment. Overall, 20 patients underwent 26 sessions of KTP laser ablation of bladder vessels. The procedure was able to stop bleeding 92% of the time and the average hematuria-free interval after ablation was 11.8 months, with a range of 1-37 months. In 13 patients (65%) hematuria resolved after 1 session of KTP laser treatment, whereas 5 patients (25%) required multiple sessions. Two patients (10%) with severe hematuria continued to have bleeding after laser treatment, which necessitated proximal diversion of urine with percutaneous nephrostomy tubes to control bleeding. CONCLUSION: This study suggests that KTP laser, with its unique photoselectivity property, is a safe, effective, and durable treatment with minimal side effects for ablation of submucosal bladder vessels in patients with RHC.

Penile cancer: organ-sparing techniques.

To compare the oncological safety of treating patients with penile cancer with conservative techniques developed to preserve function, cosmesis and psychological well-being with more radical ablative strategies. We conducted an extensive review of the literature of penile-preserving and ablative techniques and report on the oncological as well as functional outcomes. There were no randomised studies comparing penile-preserving and ablative techniques. Most studies consisted of retrospective cohorts. The quality of evidence was level 3 at best. Cancer-specific survival is similar in penile-preserving and ablative approaches for low-stage disease. Penile preservation is better for functional and cosmetic outcomes and should be offered as a primary treatment method in men with low-stage penile cancer.

Architectural heterogeneity and cribriform pattern predict adverse clinical outcome for Gleason grade 4 prostatic adenocarcinoma.

Gleason grade 4 defines a group of prostatic adenocarcinomas with a variety of architectural patterns, including poorly formed glands, fused glands, and cribriform pattern. To address the relative contribution to clinical prognosis by these distinct patterns, the histology of 241 consecutive radical prostatectomy specimens with the highest Gleason grade of 4 was reviewed. The presence of poorly formed glands, fused glands, and cribriform pattern was recorded for each case, and the types of architectural patterns present were associated with patient outcome. In this population, prostatic adenocarcinomas demonstrated architectural heterogeneity, with 17% of cases exhibiting a single Gleason grade 4 pattern, and 41% of cases exhibiting all 3 morphologic patterns. Patients exhibiting all 3 architectural patterns had lower rates of biochemical disease-free survival (66% vs. 76% at 5 y; log rank P=0.006). Twenty-two of 165 patients (13.3%) with cribriform pattern adenocarcinoma developed metastasis, whereas 2 of 76 patients (2.6%) without cribriform pattern developed metastasis at a median postoperative follow-up of 10.0 years. The presence of a cribriform pattern was an independent predictor for biochemical recurrence (hazard ratio 2.41; 95% confidence interval, 1.34-4.32; P=0.003) as well as metastasis after radical prostatectomy (hazard ratio 5.62; 95% confidence interval, 1.29-24.5; P=0.02). These results suggest that the morphologic subclassification of distinct Gleason grade 4 architectural patterns provides prognostic information beyond the current Gleason classification system.

Long-term outcomes of surgical management for nonmalignant perineal disease.

PURPOSE: A number of nonmalignant perineal diseases (focal and systemic) require surgery. The long-term outcome of various types of wound coverage for these diseases is not well described. We report the outcomes of perineal reconstruction for these diseases. MATERIALS AND METHODS: We identified 32 patients who underwent surgery from July 1995 to December 2012 for a nonmalignant conditions, including local disease (perineal gangrene and focal granulomatous/idiopathic lymphangitis) and regional/systemic disease (post-radiation lymphedema, lymphedema praecox and hidradenitis suppurativa), who had greater than 1-year followup. Wound closure was achieved by split-thickness skin graft, primary closure, musculocutaneous flap or healing by secondary intention. Long-term cosmetic/functional outcomes were measured semiquantitatively. RESULTS: Median patient age was 57 years (range 41 to 86) and median followup was 60 months (range 12 to 99). Of the patients 23 (72%) received a split-thickness skin graft, 2 (6%) underwent primary closure, 2 (6%) received a pedicled flap and 5 (16%) healed by secondary intention. Patients with perineal gangrene (21), focal granulomatous lymphangitis (4) and focal idiopathic lymphangitis (1) had favorable cosmetic/functional results regardless of closure type. All 4 patients with perineal gangrene who received a penile split-thickness skin graft and had erectile function before illness regained function after closure. Grafting for systemic lymphatic disease, such as post-radiation lymphedema in 3 cases, lymphedema praecox in 2 and hidradenitis suppurativa in 1, had mostly unfavorable cosmetic/functional long-term results. CONCLUSIONS: Wound closure, including grafts/flaps, for local cutaneous and lymphatic diseases affecting the perineum have excellent cosmetic and functional results. In contrast, grafts for regional/systemic diseases have suboptimal results and may assume the characteristics of the original disease.

Identification of nine genomic regions of amplification in urothelial carcinoma, correlation with stage, and potential prognostic and therapeutic value.

We performed a genome wide analysis of 164 urothelial carcinoma samples and 27 bladder cancer cell lines to identify copy number changes associated with disease characteristics, and examined the association of amplification events with stage and grade of disease. Multiplex inversion probe (MIP) analysis, a recently developed genomic technique, was used to study 80 urothelial carcinomas to identify mutations and copy number changes. Selected amplification events were then analyzed in a validation cohort of 84 bladder cancers by multiplex ligation-dependent probe assay (MLPA). In the MIP analysis, 44 regions of significant copy number change were identified using GISTIC. Nine gene-containing regions of amplification were selected for validation in the second cohort by MLPA. Amplification events at these 9 genomic regions were found to correlate strongly with stage, being seen in only 2 of 23 (9%) Ta grade 1 or 1-2 cancers, in contrast to 31 of 61 (51%) Ta grade 3 and T2 grade 2 cancers, p<0.001. These observations suggest that analysis of genomic amplification of these 9 regions might help distinguish non-invasive from invasive urothelial carcinoma, although further study is required. Both MIP and MLPA methods perform well on formalin-fixed paraffin-embedded DNA, enhancing their potential clinical use. Furthermore several of the amplified genes identified here (ERBB2, MDM2, CCND1) are potential therapeutic targets.

Development and validation of a 32-gene prognostic index for prostate cancer progression.

The accurate determination of the risk of cancer recurrence is an important unmet need in the management of prostate cancer. Patients and physicians must weigh the benefits of currently available therapies against the potential morbidity of these treatments. Herein we describe the development of a gene expression-based continuous risk index and a validation of this test in an independent, blinded cohort of post-radical prostatectomy (RP) patients. A gene expression signature, prognostic for prostate-specific antigen (PSA) recurrence, was identified through a bioinformatic analysis of the expression of 1,536 genes in malignant prostate tissue from a training cohort of consecutive patients treated with RP. The assay was transferred to a real-time RT-PCR platform, and a continuous risk index model was constructed based on the expression of 32 genes. This 32-gene risk index model was validated in an independent, blinded cohort of 270 RP patients. In multivariate analyses, the risk index was prognostic for risk of PSA recurrence and had added value over standard prognostic markers such as Gleason score, pathologic tumor stage, surgical margin status, and presurgery PSA (hazard ratio, 4.05; 95% confidence interval, 1.50-10.94; P = 0.0057). Furthermore, RP patients could be stratified based on the risk of PSA recurrence and the development of metastatic disease. The 32-gene signature identified here is a robust prognostic marker for disease recurrence. This assay may aid in postoperative treatment selection and has the potential to impact decision making at the biopsy stage.

Long-term oncologic outcomes after radiofrequency ablation for T1 renal cell carcinoma.

BACKGROUND: Radiofrequency ablation (RFA) of renal cell carcinoma (RCC) is used to obtain local control of small renal masses. However, available long-term oncologic outcomes for RFA of RCC are limited by small numbers, short follow-up, and lack of pathologic diagnoses. OBJECTIVE: To assess the oncologic effectiveness of RFA for the treatment of biopsy-proven RCC. DESIGN, SETTING, AND PARTICIPANTS: Exclusion criteria included prior RCC or metastatic RCC, familial syndromes, or T2 RCC. We retrospectively reviewed long-term oncologic outcomes for 185 patients with sporadic T1 RCC. Median follow-up was 6.43 yr (interquartile range [IQR]: 5.3-7.7). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The chi-square test and Wilcoxon rank-sum tests were used to compare proportions and medians, respectively. Disease-specific survival and overall survival (OS) were calculated using Kaplan-Meier analysis, then stratified by tumor stage, and comparisons were made using log-rank analysis. The 5-yr disease-free survival (DFS) and OS rates are reported. A p value <0.05 was considered statistically significant. RESULTS AND LIMITATIONS: Median tumor size was 3 cm (IQR: 2.1-3.9 cm). Tumor stage was T1a: 143 (77.3%) or T1b: 42 (22.7%). Twenty-four patients (13%) were retreated for residual disease. There were 12 local recurrences (6.5%), 6 recurrences in T1a disease (4.2%) and 6 in T1b disease (14.3%) (p=0.0196). Median time to recurrence was 2.5 yr. Local salvage RFA was performed in six patients, of whom five remain disease free at 3.8-yr median follow-up. Tumor stage was the only significant predictor of DFS on multivariate analysis. At last follow-up, 164 patients (88.6%) were disease free (T1a: n=132 [92.3%]; T1b: n=32 [76.2%]; p=0.0038). OS was similar regardless of stage (p=0.06). Five patients developed metachronous renal tumors (2.7%). Four patients developed extrarenal metastases (2.2%), three of whom died of metastatic RCC (1.6%). CONCLUSIONS: In poor surgical candidates, RFA results in durable local control and low risk of recurrence in T1a RCC. Higher stage correlates with a decreased disease-free survival. Long-term surveillance is necessary following RFA. Patient selection based on tumor characteristics, comorbid disease, and life expectancy is of paramount importance.

Transperineal template-guided prostate biopsy for patients with persistently elevated PSA and multiple prior negative biopsies.

OBJECTIVE: To evaluate the use of transperineal template-guided prostate biopsy for patients with persistently elevated PSA despite multiple negative prior biopsies. MATERIALS AND METHODS: A retrospective review was performed of patients with at least two prior prostate biopsies who underwent transperineal template-guided biopsy. Electronic medical records were reviewed to obtain relevant clinical, laboratory, and pathologic data. RESULTS: A total of 34 patients underwent transperineal template-guided biopsy. Patients had a mean of 3.7 ± 1.6 (range 2-8) prior biopsies, including prior negative transurethral resection (TUR) biopsy in 6 (17.6%) patients. Prostate cancer was detected in 17 (50%) of the 34 patients. Of these, 14 (82.4%) patients had cancer in the anterior prostate, 9 (52.9%) patients had cancer in the apical prostate, and 16 (94.1%) patients had cancer in either the anterior or apical prostate. Gleason score was 3+3 in 9 (52.9%) patients and 3+4 or greater in 7 (47.1%) patients. The mean number of positive cores was 4.5 ± 3.0 (range 1-11). Of the 17 patients with a diagnosis of cancer, 7 underwent radical prostatectomy, 7 underwent radiation therapy, 1 elected active surveillance, and 1 was deciding between surgery and radiation therapy; 1 patient received palliative chemotherapy for synchronous metastatic pancreatic carcinoma. Patients in whom cancer was detected had significantly smaller prostate volume, higher PSA, higher PSA density, and greater PSA velocity. CONCLUSIONS: Transperineal template-guided prostate biopsy is an effective technique for detecting cancer in patients with persistently elevated PSA despite multiple negative biopsies. It improves sampling of the anterior and apical prostate, and should be included as part of the diagnostic algorithm to reduce extensive repeat biopsy.

Smaller prostate gland size and older age predict Gleason score upgrading.

OBJECTIVES: Gleason score is important for prostate cancer (CaP) risk stratification and prognostication but has a significant rate of upgrading. We examined the effect of prostate size and age on upgrading of Gleason 6 CaP. MATERIALS AND METHODS: A retrospective review was performed of patients with Gleason 6 CaP who underwent radical prostatectomy from 2001 through 2010. Preoperative clinical and pathologic variables were assessed to determine association with risk of upgrading at prostatectomy. RESULTS: A total of 1,836 patients were identified with Gleason 6 on prostate biopsy. Upgrading was observed in 543 (29.6%) patients with a final Gleason score of 3+4 in 463 (25.2%), 4+3 in 49 (2.7%), and 8-10 in 31 (1.7%). On univariate logistic regression, age, prostate weight, and PSA were significant predictors of Gleason score upgrading and remained significant on multiple logistic regression. Prostate weight was inversely related to risk of upgrading. To further explore this effect, we performed multiple logistic regression to examine risk of Gleason 6, 7, or 8-10 disease in 2,493 patients with Gleason 6-10 at prostatectomy. After controlling for age and PSA, there was a progressively increased risk of Gleason 6, 7, and 8-10 disease with decreasing prostate weight. CONCLUSIONS: Older age, higher PSA, and smaller prostate gland size are associated with increased risk of Gleason score upgrading. The inverse relationship of prostate weight to risk of Gleason upgrading may be related to increased high-grade disease in smaller glands.

Impact on the clinical outcome of prostate cancer by the 2005 international society of urological pathology modified Gleason grading system.

The 2005 International Society of Urological Pathology (ISUP) Consensus Conference modified the Gleason grading system for prostate cancer. In the modified criteria, ill-defined glands with poorly formed lumina and large cribriform glands with smooth borders, classically described as Gleason pattern 3 adenocarcinoma, were redefined as Gleason pattern 4. To evaluate the clinical outcome of patients upgraded by the ISUP criteria, the histologic slides of 1240 consecutive radical prostatectomy specimens at a single institution were reviewed, and each case of adenocarcinoma was graded on the basis of the original and modified Gleason criteria. A total of 806 patients with prostate cancer of classical Gleason score 3+3=6 or 3+4=7 and modified Gleason score 6 to 8 were analyzed with a median overall follow-up of 12.6 years. In the study population, 34% of patients with classical Gleason score 3+3=6 prostate cancer were upgraded to modified Gleason score 7 or 8 by the ISUP criteria. Compared to patients with modified Gleason score 3+3=6 and patients with classical Gleason score 3+4=7, the upgraded patients were at intermediate risk for biochemical progression (paired log-rank P≤0.003) and metastasis (paired log-rank P≤0.04) after radical prostatectomy. The hazard ratio for upgrading was 1.60 (95% confidence interval, 1.09-2.35, P=0.02) for biochemical recurrence and 5.02 (95% confidence interval, 1.77-14.2, P=0.003) for metastasis. These results validate the prognostic value of the modified Gleason grading system and suggest that the recognition of an intermediate-risk histological pattern may be useful in the prognosis of patients with prostate cancer.

A close surgical margin after radical prostatectomy is an independent predictor of recurrence.

PURPOSE: The term close surgical margin refers to a tumor extending to the inked margin of the specimen without reaching it. Current guidelines state that a close surgical margin should simply be reported as negative. However, this recommendation remains controversial and relies on limited evidence. We evaluated the impact of close surgical margins on the long-term risk of biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: We identified 1,195 consecutive patients who underwent radical prostatectomy and lymphadenectomy for localized prostate cancer at our institution from 1993 to 1999. In 894 of these patients associations between margin status and location, Gleason score, pathological stage, preoperative prostate specific antigen, prostate weight and age with the risk of biochemical recurrence were examined. RESULTS: Of these 894 patients 644 (72%) had negative margins and of these patients 100 (15.5%) had close surgical margins. In the group with prostate specific antigen failure, median time to recurrence was 3.5 years. In the group without recurrence median followup was 9.9 years. Cumulative recurrence-free survival differed significantly among positive, negative and close surgical margins (p <0.001). On multivariate analysis a close surgical margin constituted a significant, independent predictor of recurrence (HR 2.1, 95% CI 1.04-4.33). Gleason score and positive margins were the strongest prognostic factors. CONCLUSIONS: In this cohort close surgical margins were independently associated with a twofold risk of postoperative biochemical recurrence. Further evaluation of the clinical significance of close surgical margins is indicated as they might be an indicator of local recurrence and of relevance when considering salvage therapy.

Complications and long-term results of salvage cystectomy after failed bladder sparing therapy for muscle invasive bladder cancer.

PURPOSE: Radical cystectomy has been the standard treatment for muscle invasive bladder cancer. Combined modality therapy involving transurethral bladder tumor resection, external beam radiation and chemotherapy is an effective alternative to cystectomy in selected patients. Salvage cystectomy is reserved for those in whom combined modality therapy fails. We characterized complications associated with salvage cystectomy. MATERIALS AND METHODS: From 1986 to 2007 of 348 patients undergoing bladder sparing therapy 102 (29%) underwent salvage cystectomy, 91 of whom were treated at Massachusetts General Hospital after receiving combined modality therapy for T2-T4aNxM0 bladder cancer. Patients underwent transurethral bladder tumor resection followed by chemoradiation (40 Gy). Early assessment was performed by cystoscopy/re-biopsy. Patients with complete response continued with consolidation chemoradiation (total dose 64 Gy). Immediate salvage cystectomy (50 of 91) was performed for persistent disease, while delayed salvage cystectomy (41 of 91) was performed for an invasive recurrence. Complications were classified using the Clavien system. RESULTS: Median patient age was 69.4 years (range 27.5 to 88.9) and median living patient followup was 12 years (range 0 to 23). Of the patients 99% (90 of 91) underwent ileal diversion. Complications of any grade within 90 days occurred in 69% (63 of 91) of patients and 16% (15 of 91) experienced major complications within 90 days. Of the patients 21% (19 of 91) required hospital readmission within 90 days. The 90-day mortality rate was 2.2% (2 of 91). Significant cardiovascular/hematological complications (pulmonary embolism, myocardial infarction, deep vein thrombosis, transfusion) within 90 days were more common in the immediate than in the delayed cystectomy group (37% vs 15%, p = 0.02). Tissue healing complications (fascial dehiscence, wound infection, ureteral stricture, anastomotic stricture, stoma/loop revisions) were more common in the delayed than in the immediate cystectomy group (35% vs 12%, p = 0.05). CONCLUSIONS: Salvage cystectomy is associated with acceptable morbidity, although complication rates are slightly higher than for other cystectomy series. Immediate cystectomies have more cardiovascular/hematological complications while delayed cystectomies have more tissue healing complications.

Animal models in urinary diversion.

We set out to critically assess the value of animal experimentation in urinary diversion through intestinal segments, as some authors question the effectiveness of animal research, criticising the methodological quality, lack of standardization, inadequate reporting and the few systematic reviews in this field. Based on a comprehensive MEDLINE literature search (MeSH database; search terms: urinary diversion, urinary reservoirs, continent, rat, dog, animal models) we retrieved and evaluated all full-length papers published in English, German, French, and Spanish languages from 1966 to 2011 reporting the use of animal models in the setting of urinary diversion. Studies were stratified according to the addressed research question. Within each category species, gender, number of animals, age at procedure, type of diversion, mortality, length of follow-up, experimental procedure and outcome were recorded and tabulated. In all, 159 articles were judged to be relevant and while there are numerous animal models only a few have been used in more than one study. Animals were used for the systematic study of new surgical techniques (93 articles) or metabolic and functional consequences of urinary reconstruction (66 articles). For the latter purpose, the most often used animal is the rat, whereas the dog model is preferred for technical experimentation. In many studies, the validity of the model is at least questionable. Animal experiments have repeatedly been conducted addressing the same question, often with striking discrepancies in outcome. Animal studies were even performed after a surgical technique had been pioneered in humans. The use of animal models in urinary diversion is far from standardized rendering the results less than ideal for comparison across studies. Due to differences in anatomy and physiology, the applicability of findings in animal experiments to clinical urology is limited. Continued effort is needed to optimise the use of animal models in experimental urology.

Long-term outcome of excisional organ sparing surgery for carcinoma of the penis.

PURPOSE: We present our experience with penile sparing surgery for localized carcinoma in situ and T1 penile squamous cell carcinoma. We report outcomes and recommendations for a penile sparing approach. MATERIALS AND METHODS: A total of 60 patients underwent penile sparing surgery for penile squamous cell carcinoma since 1995. Four patients without recurrence had less than 6 months of followup and were excluded from study. Data included disease stage, cellular differentiation, tumor site, penile sparing surgery type and recurrence information. RESULTS: Followup was adequate in 28 patients with carcinoma in situ and in 28 with T1 disease. The overall recurrence rate was 21.4% with equal recurrences of carcinoma in situ and T1 tumors (each 21.4%). Mean ± SD time to recurrence was 4.28 ± 2.81 years (range 0.5 to 11). More than 25% of recurrences developed after 5 years. Mean followup in censored patients was 5.47 ± 3.88 years (maximum 16). There was no difference in time to recurrence after carcinoma in situ and T1 tumors (p = 0.738). T1 tumors on the glans carried a slightly higher risk of recurrence (p = 0.049). At 5 years 13.8% of patients at risk had late recurrence with a mean time to recurrence of 7.25 ± 2.62 years. No patients with carcinoma in situ showed invasion or metastasis. Two patients with T1 disease presented with metastasis and 3 had late metastasis. CONCLUSIONS: Penile sparing surgery is a safe option for local control for appropriate carcinoma in situ and T1 squamous cell carcinoma of the penis. Carcinoma in situ recurrence may be re-treated with penile sparing surgery. T1 tumors that recur require more aggressive resection. Our data show significant late recurrences in patients and the need for long-term followup.