Review Article: Best Evidence Regarding Contemporary Use of Prostate Cancer Biomarkers.

INTRODUCTION: Management of prostate cancer was revolutionized by the discovery of prostate specific antigen. While prostate specific antigen is an excellent biomarker for followup after treatment, it has low specificity as a screening test and most biopsies are negative when prompted by elevated prostate specific antigen. Better prognostic biomarkers are needed to improve risk stratification to decide between treatment and observation. METHODS: We reviewed the current evidence for and against available biomarkers, and discuss the specific contexts in which biomarkers may have greatest usefulness. RESULTS: Recently introduced biomarkers attempt to improve on all aspects of the current prostate cancer management paradigm, including screening and diagnosis of disease, risk stratification and treatment allocation as well as disease monitoring after treatment. CONCLUSIONS: Each marker represents an important advance in 1 or more disease settings. Further studies are needed to determine the comparative effectiveness and cost-effectiveness of these biomarkers, and identify which tests or combinations are most useful and usable.

Management of noninvasive bladder cancers.

PURPOSE OF REVIEW: To summarize clinical management of nonmuscle-invasive bladder cancer (NMIBC) and discuss recent advances in the field. RECENT FINDINGS: NMIBC remains a common and expensive clinical entity. Prevention, early detection, and risk-adapted treatment are the mainstays of clinical management, all of which may improve as a result of recent research. Photodynamic diagnosis has demonstrated improved detection of nascent disease, and specific clinical scenarios have been identified in which photodynamic diagnosis may improve clinical outcomes. New intravesical chemotherapeutic and immunotherapeutic agents challenge our current paradigm for intermediate/high-risk NMIBC and may delay need for cystectomy after bacillus Calmette-Guerin failure. Progress in risk stratification increasingly permits individualized management regimens for NMIBC. SUMMARY: NMIBC includes many heterogeneous disease states with a variety of clinical behaviors that may evolve over time. Improved detection and risk stratification promise assignment of the optimal treatment option for an individual patient at a given time.

Real-time, near-infrared fluorescence imaging with an optimized dye/light source/camera combination for surgical guidance of prostate cancer.

PURPOSE: The prostate-specific membrane antigen (PSMA) is a surface glycoprotein overexpressed on malignant prostate cells, as well as in the neovasculature of many tumors. Recent efforts to target PSMA for imaging prostate cancer rely on suitably functionalized low-molecular-weight agents. YC-27 is a low-molecular-weight, urea-based agent that enables near-infrared (NIR) imaging of PSMA in vivo. EXPERIMENTAL DESIGN: We have developed and validated a laparoscopic imaging system (including an optimized light source, LumiNIR) that is capable of imaging small tumor burdens with minimal background fluorescence in real-time laparoscopic extirpative surgery of small prostate tumor xenografts in murine and porcine models. RESULTS: In a mouse model, we demonstrate the feasibility of using real-time NIR laparoscopic imaging to detect and surgically remove PSMA-positive xenografts. We then validate the use of our laparoscopic real-time NIR imaging system in a large animal model. Our novel light source, which is optimized for YC-27, is capable of detecting as little as 12.4 pg/mL of the compound (2.48-pg YC-27 in 200-µL agarose). Finally, in a mouse xenograft model, we demonstrate that the use of real-time NIR imaging can reduce positive surgical margins (PSM). CONCLUSIONS: These data indicate that a NIR-emitting fluorophore targeted to PSMA may allow improved surgical treatment of human prostate cancer, reduce the rate of PSMs, and alleviate the need for adjuvant radiotherapy postoperatively.

Predictors of outcome in bladder cancer.

Tumor stage and grade have largely been responsible for directing treatment algorithms in bladder cancer. However, the considerable heterogeneity of tumor biology in bladder cancer is incompletely characterized by stage and grade alone, and recent efforts to improve predictive models in bladder cancer may significantly improve accuracy and calibration. This article addresses how current nomograms and risk tables may be best used to individualize bladder cancer management.

Best evidence regarding the superiority or inferiority of robot-assisted radical prostatectomy.

Robotic-assisted laparoscopic radical prostatectomy (RALP) has enjoyed rapid adoption over the past decade without rigorous clinical studies demonstrating superior clinical outcomes over radical retropubic prostatectomy (RRP). This article reviews the literature comparing RALP and RRP with regard to oncologic, perioperative, and functional outcomes, summarizing evidence for and against the superiority of RALP.

Developments and controversies in the management of noninvasive bladder cancer.

PURPOSE OF REVIEW: To summarize recent developments and controversies in the diagnosis and management of nonmuscle invasive bladder cancer (NMIBC). RECENT FINDINGS: The majority of incident bladder cancer diagnoses are noninvasive. The mainstay of diagnosis remains cystoscopy and transurethral resection, with enhanced optical techniques potentially improving detection of nascent disease. Intravesical chemotherapeutic and immunotherapeutic agents reduce the likelihood of recurrence and progression, with novel agents showing promise. The identification of variant histology with aggressive phenotypes permits identification of patients unlikely to respond to intravesical agents, in whom early cystectomy is advocated. Risk stratification of patients with NMIBC continues to improve and should be used to inform surveillance and treatment paradigms. Tobacco cessation may improve disease-specific endpoints and overall mortality. SUMMARY: NMIBC encompasses a variety of tumors with heterogeneous natural histories, making clinical management challenging. Improved detection with novel technologies and optimization of existing treatment modalities hold promise of improving oncologic outcomes in the future.

Contemporaneous comparison of open vs minimally-invasive radical prostatectomy for high-risk prostate cancer.

OBJECTIVES: To analyze pathological and short-term oncological outcomes in men undergoing open and minimally-invasive radical prostatectomy (MIRP) for high-risk prostate cancer (HRPC; prostate-specific antigen level [PSA] >20 ng/mL, ≥ cT2c, Gleason score 8-10) in a contemporaneous series. PATIENTS AND METHODS: In total, 913 patients with HRPC were identified in the Johns Hopkins Radical Prostatectomy Database subsequent to the inception of MIRP at this institution (2002-2011) Of these, 743 (81.4%) underwent open radical retropubic prostatectomy (ORRP), 105 (11.5%) underwent robot-assisted laparoscopic radical prostatectomy (RALRP) and 65 (7.1%) underwent laparoscopic radical prostatectomy (LRP) for HRPC. Appropriate comparative tests were used to evaluate patient and prostate cancer characteristics. Proportional hazards regression models were used to predict biochemical recurrence. RESULTS: Age, race, body mass index, preoperative PSA level, clinical stage, number of positive cores and Gleason score at final pathology were similar between ORRP and MIRP. On average, men undergoing MIRP had smaller prostates and more organ-confined (pT2) disease (P = 0.02). The number of surgeons and surgeon experience were greatest for the ORRP cohort. Overall surgical margin rate was 29.4%, 34.3% and 27.7% (P = 0.52) and 1.9%, 2.9% and 6.2% (P = 0.39) for pT2 disease in men undergoing ORRP, RALRP and LRP, respectively. Biochemical recurrence-free survival among ORRP, RALRP and LRP was 56.3%, 67.8% and 41.1%, respectively, at 3 years (P = 0.6) and the approach employed did not predict biochemical recurrence in regression models. CONCLUSIONS: At an experienced centre, MIRP is comparable to open radical prostatectomy for HRPC with respect to surgical margin status and biochemical recurrence.

An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011.

OBJECTIVE: To update the 2007 Partin tables in a contemporary patient population. PATIENTS AND METHODS: The study population consisted of 5,629 consecutive men who underwent RP and staging lymphadenectomy at the Johns Hopkins Hospital between January 1, 2006 and July 30, 2011 and met inclusion criteria. Polychotomous logistic regression analysis was used to predict the probability of each pathologic stage category: organ-confined disease (OC), extraprostatic extension (EPE), seminal vesicle involvement (SV+), or lymph node involvement (LN+) based on preoperative criteria. Preoperative variables included biopsy Gleason score (6, 3+4, 4+3, 8, and 9-10), serum PSA (0-2.5, 2.6-4.0, 4.1-6.0, 6.1-10.0, greater than 10.0 ng/mL), and clinical stage (T1c, T2c, and T2b/T2c). Bootstrap re-sampling with 1000 replications was performed to estimate 95% confidence intervals for predicted probabilities of each pathologic state. RESULTS: The median PSA was 4.9 ng/mL, 63% had Gleason 6 disease, and 78% of men had T1c disease. 73% of patients had OC disease, 23% had EPE, 3% had SV+ but not LN+, and 1% had LN+ disease. Compared to the previous Partin nomogram, there was no change in the distribution of pathologic state. The risk of LN+ disease was significantly higher for tumours with biopsy Gleason 9-10 than Gleason 8 (O.R. 3.2, 95% CI 1.3-7.6). The c-indexes for EPE vs. OC, SV+ vs. OC, and LN+ vs. OC were 0.702, 0.853, and 0.917, respectively. Men with biopsy Gleason 4+3 and Gleason 8 had similar predicted probabilities for all pathologic stages. Most men presenting with Gleason 6 disease or Gleason 3+4 disease have <2% risk of harboring LN+ disease and may have lymphadenectomy omitted at RP. CONCLUSIONS: The distribution of pathologic stages did not change at our institution between 2000-2005 and 2006-2011. The updated Partin nomogram takes into account the updated Gleason scoring system and may be more accurate for contemporary patients diagnosed with prostate cancer.

Incidental testicular lesions found during infertility evaluation are usually benign and may be managed conservatively.

PURPOSE: Hypoechoic lesions on scrotal ultrasonography are often considered germ cell tumors and radical orchiectomy is recommended. We retrospectively reviewed the findings at 1 center in men with ultrasonographically detected testicular lesions found during evaluation of severe male infertility. MATERIALS AND METHODS: A total of 145 men with nonobstructive azoospermia at 1 center underwent ultrasonographic analysis before diagnostic or therapeutic testicular biopsy. Mean age was 34 +/- 0.6 years (range 21 to 63). All men were azoospermic. Mean serum follicle-stimulating hormone was 25 IU/l. Of the men 26% had a history of cryptorchidism and 3 patients had a history of testis tumor. No other risk factors for testis cancer were identified for any patient. All sonographic lesions were followed with serial ultrasound examinations or were biopsied/excised. All men had tumor markers tested and the results were negative. RESULTS: Of 145 men referred for azoospermia who underwent ultrasonographic analysis before biopsy 49 (34%) showed a focal sonographic abnormality. A hypoechoic lesion was seen in 20 patients (14%), a hyperechoic lesion was seen in 10 (7%) and a heterogeneous appearance to a region of testicular parenchyma was seen in 19 patients (13%). Some lesions classified as hypoechoic demonstrated hyperechoic or heterogeneous interior components. Two of the patients with hypoechoic lesions were lost to followup. Of the remaining 18 patients 11 had lesions less than 5 mm in greatest diameter and all of these were confirmed to be benign. Only 1 patient had a seminoma, and that patient had an inguinal testis with a mass detected on routine ultrasound. All other patients with hyperechoic or heterogeneous areas on ultrasound with subsequent tissue diagnoses were found to have benign lesions. CONCLUSIONS: Men with severe infertility who are found to have incidental testicular lesions and negative tumor markers, especially lesions less than 5 mm, may be initially observed with serial scrotal ultrasound examinations. Enlarging lesions or those of greater dimension should be considered for histological examination.