Influence of pelvic lymph node dissection and node-positive disease on biochemical recurrence, secondary treatment, and survival after radical prostatectomy in men with prostate cancer.

BACKGROUND: The benefit of pelvic lymph node dissection (PLND) at radical prostatectomy (RP) remains unclear given the low prevalence of known nodal disease (pN1) and concerns about its therapeutic utility. OBJECTIVE: To characterize the impact of PLND and secondary treatment on oncologic outcomes. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of men who underwent primary RP with PLND for prostate cancer (PCa) at our institution since 2003. Men stratified by nodal status. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Outcomes include biochemical recurrence-free survival (bRFS), overall survival, and PCa-specific mortality (PCSM). Multivariable Cox regression models used for each outcome. RESULTS AND LIMITATIONS: Of 1,543 men who underwent primary RP, 174 (11%) had pN1 disease. Median follow-up was 34 months (interquartile range, 15-62). Seven-year outcomes were similar whether less than or ≥14 LNs dissected. Among node-positive patients, 29% had undetectable (UDT) prostate-specific antigen (PSA), 11% had UDT PSA + adjuvant therapy, and 60% had detectable PSA, and 7-year bRFS differed (75% for UDT PSA, 90% for UDT + adjuvant therapy, 38% for detectable PSA, p < .01). Survival outcomes did not differ. In multivariable analysis, detectable PSA (vs. UDT, HR 5.2, 95% CI 2.0-13.3) associated with worse bRFS. After salvage treatment, 7-year outcomes did not differ between groups. Study limited by retrospective review.

Pleiotropic role for MYCN in medulloblastoma.

Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Sonic Hedgehog (SHH) signaling drives a minority of MB, correlating with desmoplastic pathology and favorable outcome. The majority, however, arises independently of SHH and displays classic or large cell anaplastic (LCA) pathology and poor prognosis. To identify common signaling abnormalities, we profiled mRNA, demonstrating misexpression of MYCN in the majority of human MB and negligible expression in normal cerebella. We clarified a role in pathogenesis by targeting MYCN (and luciferase) to cerebella of transgenic mice. MYCN-driven MB showed either classic or LCA pathologies, with Shh signaling activated in approximately 5% of tumors, demonstrating that MYCN can drive MB independently of Shh. MB arose at high penetrance, consistent with a role for MYCN in initiation. Tumor burden correlated with bioluminescence, with rare metastatic spread to the leptomeninges, suggesting roles for MYCN in both progression and metastasis. Transient pharmacological down-regulation of MYCN led to both clearance and senescence of tumor cells, and improved survival. Targeted expression of MYCN thus contributes to initiation, progression, and maintenance of MB, suggesting a central role for MYCN in pathogenesis.

Management of intermediate-risk prostate cancer with active surveillance: never or sometimes?

PURPOSE OF REVIEW: Active surveillance has become the recommended management strategy for most patients with low-risk prostate cancer (PCa), but whether surveillance criteria can be expanded without compromising oncologic outcomes is a matter of debate. Whereas there is essentially uniform consensus that those with low-risk disease can be safely managed with AS, those with intermediate-risk disease, younger men and African-American men are often excluded. RECENT FINDINGS: Outcome data for intermediate-risk patients managed by active surveillance demonstrate acceptable oncologic outcomes, but there is also evidence that such patients have higher rates of progression, adverse disease and metastatic disease. Studies evaluating the utility of quantitative Gleason grade, the use of biomarkers and multiparametric MRI are emerging and are likely to refine risk assessment. Literature describing the effects of young age on outcomes is lacking, but early data appear promising. Data on African-American men show varied results that are sometimes contradictory and further investigation is needed to elucidate the impact of race, independent of socioeconomic status. SUMMARY: Patients with intermediate-risk PCa should not be excluded from active surveillance based on any single, borderline criterion; rather, treatment decisions should be based on the full clinical picture, and may be further refined by patient characteristics and adjunctive tools.

Transition to Value-based Healthcare: Development, Implementation, and Results of an Optimal Surgical Care Framework at a National Cancer Institute-designated Comprehensive Cancer Center.

BACKGROUND: The continued rise in healthcare expenditures has not produced commensurate improvements in patient outcomes, leading US healthcare stakeholders to emphasize value-based care. Transition to such a model requires all team members to adopt a new strategic and organizational framework. OBJECTIVE: To describe and report a strategy for the implementation of a novel patient-centered value-based "optimal surgical care" (OSC) framework, with validation and cost analysis in kidney surgery. DESIGN, SETTING, AND PARTICIPANTS: An observational study of care episodes at a single institution from 2014 to 2019 was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multidisciplinary teams defined OSC by core and procedure-specific metrics using a combination of provider-based ("bottom-up") and "clinical leadership"-based ("top-down") strategies. Baseline OSC rates across were established, while identifying proportions of OSC achieved by coefficient of variation (CV) in total direct costs. Multivariable linear regression comparing cost between OSC and non-OSC encounters was performed, adjusting for patient characteristics. RESULTS AND LIMITATIONS: An analysis of 30 261 perioperative care episodes was performed. Following the implementation of an OSC framework, there was an increase in OSC rates across all procedure buckets using core (25%) and procedure-specific (26%) metrics. Among the tumors tested, kidney cancer surgical episodes held the highest OSC rate improvement (67%) with lowest variability in cost (CV 0.5). OSC was associated with significant total cost savings across all tumor types after adjusting for inflation (p < 0.05). Compared with non-OSC episodes, a significant reduction in the cost ratio of OSC was noted for renal surgery (p < 0.01), with estimated costs savings of $2445.87 per OSC encounter. CONCLUSIONS: Institutional change directing efforts toward optimizing surgical care and emphasizing value rather than focusing solely on expense reduction is associated with improved outcomes, while potentially reducing costs. The strategy for implementation requires serial performance analyses, engaging and educating providers, and continuous ongoing adjustments to achieve durable results. PATIENT SUMMARY: In this study, we report our strategy and outcomes for transitioning to a value-based healthcare model using a novel "optimal surgical care" framework at a National Cancer Institute-designated comprehensive cancer center. We observed an increase in optimal surgical care episodes across all specialties after 5 yr, with a potential associated reduction in cost expenditure. We conclude that the key to a successful and sustained transition is the implementation strategy, focusing on continual review and provider engagement.

Robotic renal surgery for renal cell carcinoma with inferior vena cava thrombus.

Surgical management of renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is inherently complex, posing challenges for even the most experienced urologists. Until the mid-2000s, nephrectomy with IVC thrombectomy was exclusively performed using variations of the open technique initially described decades earlier, but since then several institutions have reported their robotic experiences. Robotic IVC thrombectomy was initially reported for level I and II thrombi, and more recently in higher-lever III thrombi. In general, the robotic approach is associated with less blood loss and shorter hospital stays compared to the open approach, low rates of open conversion in reported cases, relatively low rates of high-grade complications, and favorable overall survival on short-term follow-up in limited cohorts. Operative times are longer, costs are significantly higher, and left-sided tumors always require intraoperative repositioning and usually require preoperative embolization. To date, criteria for patient selection or open conversion have not been defined, and long-term oncologic outcomes are lacking. While the early published robotic experience demonstrates feasibility and safety in carefully selected patients, longer-term follow-up remains necessary. Patient selection, indications for open conversion, logistics of conversion particularly in emergent settings, necessity and safety of preoperative embolization, the value proposition, and long-term oncologic outcomes must all be clearly defined before this approach is widely adopted.

The future of "Retro" robotic partial nephrectomy.

Partial nephrectomy (PN) is the gold standard treatment for appropriately selected renal masses. Recent surgical advancements and adoption of the robotic technique has led to greater adoption of nephron-sparing surgery. Robotic PN was initially described via the transperitoneal (TP) approach, however, retroperitoneal (RP) access is possible and in some cases more desirable. In the RP approach, the kidney is accessed from its posterior surface and the intraperitoneal space is avoided. The RP approach to PN has the benefit of avoiding intraperitoneal viscera and colonic mobilization in patients with extensive prior abdominal surgery. The technique also eliminates the need for renal unit rotation in patients with posterior tumors and affords access to masses directly posterior to the renal hilum. The RP and TP approach to PN have shown similar oncologic and perioperative outcomes. Several recent studies have reported shorter operative times and lengths of stay (LOS) with comparable warm ischemia times for the RP approach when compared to transperitoneal PN (tPN). Given the indispensable deliverables of this approach in select patients, robotic retroperitoneal PN (rPN) should be in the armamentarium of a versatile urologic kidney surgeon. This review describes the current state of rPN and compares the indications and outcomes of the TP and RP approaches.

Renal mass biopsy: A strategy to reduce associated costs and morbidity when managing localized renal masses.

INTRODUCTION AND OBJECTIVES: Renal mass biopsy (RMB) has not been widely adopted in evaluating small renal mass due to concerns for safety, efficacy, and its perceived lack of consequence on management decisions. We assess the potential cost savings and morbidity avoidance of routine RMB on cT1 renal masses undergoing robotic-assisted partial nephrectomy (RAPN). METHODS: We identified n = 920 consecutive RAPN pT1 renal masses and n = 429 consecutive RMBs for cT1 renal masses over 12 years. Using a novel pathological-based risk classification system for cT1 renal masses, we evaluated the morbidity and costs of our RAPN and RMB cohorts. We then define four clinical scenarios where RMB could potentially delay and/or avoid intervention in our pT1 RAPN cohort and model potential complications prevented and cost savings utilizing common clinical scenarios. RESULTS: Using our risk stratification system in RAPN patients, final histology was classified as benign in n=174 (18.9%) cases, very low-risk (n = 62 [7%]), low-risk (n = 383 [42%]), and high-risk (n = 301 [33%]), respectively. We identified n = 116 (12.6%) Clavien graded peri-operative complications. In our RMB patients, 120 (27.9%), 17 (3.9%), 240 (55.9%), 52(12.1%) were benign, very low, low and high-risk tumors. The median total direct cost for RAPN was $6955/case compared to $1312/case for RMB. If we established a primary goal to avoid immediate extirpative surgery in benign renal tumors, in the elderly (>70 y) with very low-risk tumors and/or those with high renal functional risks (≥ CKD3b), or competing risks (ASA ≥ 3), RMB could have reduced direct costs by approximately 20% and avoided n = 39 Clavien graded complications, seven readmissions, three transfusions, and two returns to the OR. With the additional cost of performing RMB on those not initially biopsied, the net cost saving would be approximately $1.2 million with minimal added complications while still treating high-risk tumors. CONCLUSIONS: Routine RMB before intervention results in cost-saving and complication avoidance. Given the limitations of biopsy, shared decision-making is mandatory. Biopsy should be considered prior to intervention in at-risk populations.

Feasibility and Outcomes of Renal Mass Biopsy for Anatomically Complex Renal Tumors.

OBJECTIVE: To compare the feasibility and outcomes of renal mass biopsies (RMB) of anatomically complex vs non-complex renal masses. METHODS: Our institutional renal tumor database was queried for patients who underwent RMB between 2005 and 2019 and with available nephrometry score. Complex masses were: (1) small (<2 cm), (2) entirely endophytic (nephrometry E=3), (3) hilar (h) or (4) partially endophytic (E=2) and anterior. Demographic and pathologic data were compared. Biopsies were deemed adequate if they resulted in a diagnosis. Concordance with surgical pathology was assessed. These were both presented using proportions. Factors associated with biopsy outcomes were identified using multivariable logistic regression. RMB sensitivity and specificity were calculated using contingency methods. RESULTS: A total of 306 RBMs were included, 179 complex and 127 non-complex. A total of 199 (65%) had an extirpative procedure. Complex lesions were less likely to have an adequate biopsy (89% vs 96%, P = .03), and to be concordant with final surgical pathology from an oncologic standpoint (89% vs 97%, P = .03). There was no significant difference in concordance of histology (76% vs 86%, P = .10) or grade (48 vs 51%, P = .66). On multivariable analyses, only male gender was associated with biopsy adequacy (OR 3.31, 95% CI 1.28-8.55, P = .01). Our overall sensitivity was 93%, specificity 93%, and accuracy 93%. There were no significant differences over time in biopsy outcomes during the study period. CONCLUSION: RMB of complex lesions is associated with excellent diagnostic yield, albeit lower than non-complex lesions. RMB should not be deferred in cases of anatomically complex lesions where additional data could improve clinical decision-making.

Refractory hypertension due to unilateral renal lymphangiectasia: An uncommon case with a surgical solution.

We describe a case of unilateral renal lymphangiectasia (RLM) in a 30-year-old male with severe, refractory hypertension (HTN) and end-organ effects despite five anti-hypertensives. After diagnostic testing, the patient ultimately underwent a successful right laparoscopic nephrectomy with significant improvement of HTN. We review the literature regarding the pathophysiology and management strategies of HTN in patients with renal lymphangiectasia.

Neoadjuvant checkpoint inhibition in renal cell carcinoma associated Stauffer's syndrome.

Stauffer's syndrome is a paraneoplastic phenomenon associated with renal cell carcinoma (RCC) characterized by cholestatic hepatitis. We explore the effects of perioperative immunotherapy in a case of Stauffer's syndrome. A 70-year-old female with a locally advanced clear cell RCC (ccRCC) developed severe hyperbilirubinemia. The patient's cholestasis progressed despite initial systemic immunotherapy, but improved after cytoreductive nephrectomy. The patient continued immunotherapy post-operatively and regained normalized hepatic function. To our knowledge, this is the first case reporting use of systemic immunotherapy with surgery in Stauffer's syndrome, and we provide clinical insight into a treatment regimen which may be employed in future cases.

Bacillus Calmette-Guérin Packaged for Percutaneous Vaccination Can Be Safely Used for Intravesical Instillation in Patients with Urothelial Carcinoma of the Bladder.

INTRODUCTION: Bacillus Calmette-Guérin production is limited worldwide with stuttering shortages affecting patient access. Our institution received 50 vials of bacillus Calmette-Guérin labeled for percutaneous administration, and upon discussion with our clinical team and approval by the Pharmacy and Therapeutics Committee we used the percutaneous formulation in place of the intravesical formulation. We report our experience. METHODS: Between February and April 2019 patients were treated with a third of a vial dose either with percutaneous or intravesical bacillus Calmette-Guérin. American Urological Association Symptom Score and Quality of Life survey and an additional 6-question survey (querying presence of suprapubic pain, hematuria, fevers, malaise, skin rashes, testicular/groin pain) were administered. Statistical analyses comparing the 2 groups were performed with SPSS version 22 software. RESULTS: A total of 30 patients with 73 intravesical instillations were evaluated with 34 patients receiving intravesical and 39 percutaneous bacillus Calmette-Guérin. We found no significant differences when comparing intravesical vs percutaneous bacillus Calmette-Guérin groups in terms of American Urological Association Symptom Score (6.1 vs 6.9, p=0.177), Quality of Life score (1.3 vs 1.7, p=0.132), fevers (2.9% vs 0%, p=0.300), hematuria (14.7% vs 2.8%, p=0.075), suprapubic pain (10.1% vs 4.3%, p=0.129), skin rashes (1.4% vs 0%, p=0.307) and feeling of general fatigue and malaise (15.7% vs 8.6%, p=0.126). CONCLUSIONS: Intravesical instillation of percutaneous bacillus Calmette-Guérin appears to be a safe alternative to intravesical bacillus Calmette-Guérin during times of shortage. Development of additional strains, use of alternative intravesical therapies and incentivizing bacillus Calmette-Guérin production through policy change and/or alternative funding may also help avoid bacillus Calmette-Guérin supply shortages in the future.

Driving Neuronal Differentiation through Reversal of an ERK1/2-miR-124-SOX9 Axis Abrogates Glioblastoma Aggressiveness.

Identifying cellular programs that drive cancers to be stem-like and treatment resistant is critical to improving outcomes in patients. Here, we demonstrate that constitutive extracellular signal-regulated kinase 1/2 (ERK1/2) activation sustains a stem-like state in glioblastoma (GBM), the most common primary malignant brain tumor. Pharmacological inhibition of ERK1/2 activation restores neurogenesis during murine astrocytoma formation, inducing neuronal differentiation in tumorspheres. Constitutive ERK1/2 activation globally regulates miRNA expression in murine and human GBMs, while neuronal differentiation of GBM tumorspheres following the inhibition of ERK1/2 activation requires the functional expression of miR-124 and the depletion of its target gene SOX9. Overexpression of miR124 depletes SOX9 in vivo and promotes a stem-like-to-neuronal transition, with reduced tumorigenicity and increased radiation sensitivity. Providing a rationale for reports demonstrating miR-124-induced abrogation of GBM aggressiveness, we conclude that reversal of an ERK1/2-miR-124-SOX9 axis induces a neuronal phenotype and that enforcing neuronal differentiation represents a therapeutic strategy to improve outcomes in GBM.

Robotic Inferior Vena Cava Thrombectomy: Are We Entering the House Through an Attic Window?

While feasible, it is unclear whether robotic inferior vena cava thrombectomy affords significant benefits. Outcomes are acceptable in carefully selected patients, but the approach is not applicable to all-comers. Higher costs are a challenge for health care systems and the value proposition for this approach is undefined.

Effects of Initial Gleason Grade on Outcomes during Active Surveillance for Prostate Cancer.

BACKGROUND: Whether men with Gleason 3+4 prostate cancer are appropriate active surveillance (AS) candidates remains a matter of debate. OBJECTIVE: to evaluate the effects of initial Gleason grade 3+3 or 3+4 on clinical outcomes during AS. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed outcomes for men on AS between 1990 and 2016 with Gleason 3+3 or 3+4 who had two or more biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated associations of diagnostic grade with reclassification (upgrade ≥ 3+4), treatment, metastasis, adverse surgical pathology, and biochemical recurrence (BCR) after deferred radical prostatectomy (RP), with a sensitivity analysis for the amount of pattern 4 disease. RESULTS AND LIMITATIONS: Of 1243 men, 1119 (90%) had Gleason 3+3 and 124 (10%) 3+4 on initial biopsy. The 5-yr unadjusted reclassification-free survival was 49% regardless of grade, while patients with Gleason 3+4 had lower treatment-free survival (49% vs 64%; p<0.01). On multivariate Cox analysis, grade was associated with lower risk of reclassification (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.46-0.95) and higher risk of treatment (HR 1.37, 95% CI 1.01-1.85). After RP, patients starting with Gleason 3+4 had lower unadjusted 2-yr BCR-free survival (69% vs 93%; p=0.01) and a higher risk of recurrence (HR 3.67, 95% CI 1.30-10.36). Grade was not associated with metastasis (<1% at 5 yr) or adverse pathology. In sensitivity analyses, a single high-grade core was associated with lower risk of reclassification and multiple high-grade cores were associated with a higher risk of treatment. The number of high-grade cores was not independently associated with BCR. Limitations include selection bias, a limited number of intermediate-risk patients, and length of follow-up. CONCLUSIONS: Gleason 3+4 at diagnosis was associated with risk of reclassification, treatment, and BCR. The number of high-grade cores may help in stratifying men with Gleason 3+4 disease. PATIENT SUMMARY: Some men with Gleason 3+4 prostate cancer may be appropriate surveillance candidates, but longer follow-up and evaluation of more patients are necessary.

Ultrasound Guidance for Renal Tract Access and Dilation Reduces Radiation Exposure during Percutaneous Nephrolithotomy.

Purposes. To present our series of 38 prone percutaneous nephrolithotomy procedures performed with renal access and tract dilation purely under ultrasound guidance and describe the benefits and challenges accompanying this approach. Methods. Thirty-eight consecutive patients presenting for percutaneous nephrolithotomy for renal stone removal were included in this prospective cohort study. Ultrasonographic imaging in the prone position was used to obtain percutaneous renal access and guide tract dilation. Fluoroscopic screening was used only for nephrostomy tube placement. Preoperative, intraoperative, and postoperative procedural and patient data were collected for analysis. Results. Mean age of patients was 52.7 ± 17.2 years. Forty-five percent of patients were male with mean BMI of 26.1 ± 7.3 and mean stone size of 27.2 ± 17.6 millimeters. Renal puncture was performed successfully with ultrasonographic guidance in all cases with mean puncture time of 135.4 ± 132.5 seconds. Mean dilation time was 11.5 ± 3.8 min and mean stone fragmentation time was 37.5 ± 29.0 min. Mean total operative time was 129.3 ± 41.1. No patients experienced any significant immediate postoperative complication. All patients were rendered stone-free and no additional secondary procedures were required. Conclusions. Ultrasound guidance for renal access and tract dilation in prone percutaneous nephrolithotomy is a feasible and effective technique. It can be performed safely with significantly reduced fluoroscopic radiation exposure to the patient, surgeon, and intraoperative personnel.

Adopting Ultrasound Guidance for Prone Percutaneous Nephrolithotomy: Evaluating the Learning Curve for the Experienced Surgeon.

OBJECTIVES: To define the learning curve associated with adopting ultrasound guidance for prone percutaneous nephrolithotomy (PCNL) for the experienced surgeon. METHODS: A prospective cohort study of consecutive patients undergoing PCNL with ultrasound guidance for renal tract access and dilation was performed. Clinical data reviewed included success in gaining renal access with ultrasound guidance, total fluoroscopic screening time, and radiation exposure dose. PCNL cases performed with fluoroscopic guidance matched for stone size served as control cases. RESULTS: One hundred consecutive ultrasound-guided procedures performed by a single experienced endourologist were divided into five experience groups. Significant improvement in renal access success rate with ultrasound was seen after 20 cases (p < 0.05). Total fluoroscopic screening time, radiation exposure dose, and operative time were also statistically significantly improved over the study period. When compared with fluoroscopy-guided PCNL, significant decreases in total fluoroscopic screening time (33.4 ± 35.3 seconds vs 157.5 ± 84.9 seconds, p < 0.05) and radiation exposure (7.0 ± 8.7 mGy vs 47.8 ± 45.9 mGy, p < 0.05) were seen. No differences in complication rates were found. CONCLUSIONS: Ultrasound-guided renal access for PCNL can be performed effectively after 20 cases. Transition to the use of ultrasound will quickly reduce radiation exposure for patients and intraoperative personnel.

Ultrasound Guidance to Assist Percutaneous Nephrolithotomy Reduces Radiation Exposure in Obese Patients.

OBJECTIVE: To evaluate the impact of body mass index (BMI) on perioperative outcomes and radiation exposure for ultrasound (US)-guided percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: Data were prospectively collected for consecutive patients who underwent PCNL at the University of California, San Francisco, from July 2013 to November 2015. Patients were divided into 3 groups according to their BMI: <25 (normal weight), 25-29.9 (overweight), and >30 (obese) kg/m2. Perioperative outcomes were compared between patients who underwent US-guided vs fluoroscopy-guided PCNL. RESULTS: One hundred thirty-five patients were enrolled; 93 cases were performed under US and 42 under fluoroscopic guidance. US successfully guided renal access in 76.9% of normal weight, 79.0% of overweight, and 45.7% of obese patients (P < .05). Mean fluoroscopic screening time and radiation exposure dose were reduced for US compared to fluoroscopy cases across all BMI categories (P < .05). As BMI increased, radiation exposure dose rose disproportionately faster compared to screening time (P < .001). No significant differences among the BMI groups were found with regard to complication rate, hospital stay, and stone-free status. CONCLUSION: US-guided PCNL may be more difficult in obese patients, but with its use, the overweight and obese experience the largest absolute reduction in radiation exposure. Because these patients are inherently at greater risk for radiation exposure compared to normal weight patients, they may benefit the most from adoption of US for PCNL.

Ultrasound-Guided Renal Access for Percutaneous Nephrolithotomy: A Description of Three Novel Ultrasound-Guided Needle Techniques.

Ultrasound-guided renal access for percutaneous nephrolithotomy (PCNL) is a safe, effective, and low-cost procedure commonly performed worldwide, but a technique underutilized by urologists in the United States. The purpose of this article is to familiarize the practicing urologist with methods for ultrasound guidance for percutaneous renal access. We discuss two alternative techniques for gaining renal access for PCNL under ultrasound guidance. We also describe a novel technique of using the puncture needle to reposition residual stone fragments to avoid additional tract dilation. With appropriate training, ultrasound-guided renal access for PCNL can lead to reduced radiation exposure, accurate renal access, and excellent stone-free success rates and clinical outcomes.

Management of an increasing prostate-specific antigen level after negative prostate biopsy.

Patients who have a previously negative biopsy in the setting of clinical suspicion of prostate cancer still have a high risk of harboring significant undiagnosed disease. Various markers such as prostate-specific antigen (PSA) velocity, PSA density, PCA3, and newer markers may aid in repeat biopsy selection. Repeating the same biopsy procedure in such patients does not yield high cancer detection rates. More anteriorly directed transrectal or transperineal biopsies are indicated. Multiparametric magnetic resonance imaging can detect abnormal areas, and lesion-targeted biopsies can improve the cancer detection rate.