Abhinav Sidana

Treatment decision-making for localized prostate cancer: what younger men choose and why.

The literature lacks knowledge about information preferences and decision‐making in young prostate cancer patients. This study provides insight into information sources consulted and factors dictating treatment decision‐making in young prostate cancer patients.

Cyclophosphamide Unmasks an Antimetastatic Effect of Local Tumor Cryoablation

Cryoablation of a solitary tumor mass releases intact tumor antigens and can induce protective antitumor immunity but has limited efficacy in the treatment of established metastatic cancer. Cyclophosphamide (Cy), an anticancer drug, selectively depletes regulatory T cells (Tregs) and attenuates suppression of antitumor immunity. We used a BALB/c mouse model of metastatic colon cancer to investigate the systemic antitumor effects of in situ cryotherapy alone or in combination with 200 mg/kg i.p. Cy. When combined with Cy, cryoablation was significantly more effective than either surgical excision or cautery at inducing systemic antitumor immunity, resulting in the cure of a fraction of animals with established metastatic disease and resistance to tumor rechallenge. Lymphocytes from cured animals contained an expanded population of tumor-specific, interferon-γ producing T cells and transferred antitumor immunity to naive recipients. Depletion of CD8+ cells significantly impaired the adoptive transfer of antitumor immunity. Furthermore, treatment with Cy and cryoablation was associated with a significant decrease in the ratio of regulatory to effector CD4+ T cells. The combination of tumor cryoablation and Cy induces potent, systemic antitumor immunity in animals with established metastatic disease.

Single-Center Comparative Oncologic Outcomes of Surgical and Percutaneous Cryoablation for Treatment of Renal Tumors

PURPOSE To compare outcomes between patients undergoing surgical and percutaneous cryoablation for treatment of renal masses and identify prognostic variables that determine survival. PATIENTS AND METHODS We retrospectively evaluated the medical records of 194 patients who underwent cryoablation for renal tumors between 1997 and 2008 at a single large center. Patient demographics, tumor characteristics, perioperative data, and follow-up details were recorded. Univariate and multivariate Cox proportional hazards analysis was performed to identify predictors of overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). RESULTS Cryoablation was performed percutaneously (PCA) in 141 patients for 154 tumors, while 53 patients were treated surgically (SCA) using an open or laparoscopic approach for 54 tumors. Mean follow-up was 44.5 months in SCA and 36.1 months in PCA. PCA had a shorter duration of hospital stay (0.7 days vs 3.2 days, P<0.0001). The rate of residual (P=0.38) and recurrent disease (P=0.18) was not significantly different between the two groups. Five-year OS, CSS, and RFS were 78.81%, 100%, and 85.23% for SCA, and 77.71%, 98%, and 95.56% for PCA, respectively; the type of approach was not predictive of OS, CSS, and RFS. CONCLUSIONS SCA and PCA both provide adequate oncologic control for renal masses. Duration of hospital stay was lower in patients undergoing PCA.

Missing the Mark: Prostate Cancer Upgrading by Systematic Biopsy over Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Biopsy

Purpose: Multiparametric magnetic resonance imaging and fusion biopsy detect more high risk prostate cancer and less low risk prostate cancer than systematic biopsy. However, there remains a small subset of patients in whom systematic biopsy captures higher grade disease than fusion biopsy. We sought to identify potential mechanisms of the failure of fusion biopsy in the detection of clinically significant prostate cancer. Materials and Methods: We reviewed a prospectively maintained database of patients who underwent multiparametric magnetic resonance imaging followed by fusion biopsy and systematic biopsy from 2007 to 2014. In patients in whom disease was upgraded to clinically significant disease (Gleason 7 or greater) by systematic biopsy over fusion biopsy, independent re‐review of magnetic resonance imaging, archived biopsy imaging and whole mount pathology as well as needle coordinate mapping were performed. Multivariate logistic regression analysis was done to determine predictors of upgrading by systematic biopsy. Results: Disease was upgraded based on systematic biopsy over fusion biopsy in 135 of 1,003 patients (13.5%), of whom only 62 (6.2%) were upgraded to intermediate (Gleason 7) and high risk (Gleason 8 or greater) prostate cancer (51 or 5.1% and 11 or 1.1%, respectively). On multivariate analysis lower prostate specific antigen (p <0.001), higher magnetic resonance imaging prostate volume (p <0.001) and a lower number of target cores (p = 0.001) were predictors of upgrading by systematic biopsy. Main mechanisms of under grading by fusion biopsy included multiparametric magnetic resonance imaging reader oversight, presence of magnetic resonance imaging invisible cancer, fusion biopsy technique error and intralesion Gleason heterogeneity. Conclusions: Magnetic resonance imaging and fusion biopsy rarely missed clinically significant prostate cancer as only 62 of 1,003 cases (6.2%) were upgraded to clinically significant disease by systematic biopsy. Imaging and biopsy techniques are continually refined. Further studies will help clarify mechanisms of fusion biopsy failure and the patient populations that benefit from systematic biopsy in addition to fusion biopsy.

Complications of Renal Cryoablation: A Single Center Experience

PURPOSE We describe perioperative complications associated with renal cryoablation and identify potential risk factors for certain complications. MATERIALS AND METHODS We retrospectively analyzed the medical records of patients with unifocal renal masses treated with cryosurgery at a single center between 1997 and 2007. All complications associated with these procedures were documented and classified into grades 1 to 5 by the Clavien surgical complication classification. In-depth analysis was done to identify potential risk factors for the most common complications. RESULTS We evaluated 101 percutaneous, 52 laparoscopic and 9 open procedures. Complications were noted in 38 procedures (23.5%), including grades 1 to 4 in 19 (11.7%), 8 (4.9%), 5 (3.1%) and 6 (3.7%), respectively, as the severest complication. The most common complication was flank pain (11 procedures), followed by perinephric hematoma and cardiovascular complications (10 each). Mass size (p = 0.001), number of cryoablation probes (p <0.001) and chronic anticoagulation (p <0.05) were associated with an increased incidence of significant hematoma. Cardiovascular complications were more common when upper pole lesions were treated, and when an open approach was used (each p <0.05). Respiratory complications occurred in 7 procedures and were associated with patient age (p <0.05) and mass size (p <0.01). CONCLUSIONS Cryoablation is a relatively safe procedure with a low complications rate in properly selected patients. We identified potential risk factors that may help identify patients most at risk for certain complications and consequently assist in preprocedural planning and counseling.

Complications of renal cryoablation: a single center experience

J Urol. 2010; 184: 42-7Purpose: We describe perioperative complications associated with renal cryoablation and identify potential risk factors for certain complications.Materials and Methods: We retrospectively analyzed the medical records of patients with unifocal renal masses treated with cryosurgery at a single center between 1997 and 2007. All complications associated with these procedures were documented and classified into grades 1 to 5 by the Clavien surgical complication classifica-tion. In-depth analysis was done to identify potential risk factors for the most common complications.Results: We evaluated 101 percutaneous, 52 laparoscopic and 9 open procedures. Complications were noted in 38 procedures (23.5%), including grades 1 to 4 in 19 (11.7%), 8 (4.9%), 5 (3.1%) and 6 (3.7%), respectively, as the severest complication. The most common complication was flank pain (11 procedures), followed by perinephric hematoma and cardiovascular complications (10 each). Mass size (p = 0.001), number of cryoab-lation probes (p <0.001) and chronic anticoagulation (p <0.05) were associated with an increased incidence of significant hematoma. Cardiovascular complications were more common when upper pole lesions were treated, and when an open approach was used (each p <0.05). Respiratory complications occurred in 7 procedures and were associated with patient age (p <0.05) and mass size (p <0.01). Conclusions: Cryoablation is a relatively safe procedure with a low complications rate in properly selected pa-tients. We identified potential risk factors that may help identify patients most at risk for certain complications and consequently assist in preprocedural planning and counseling.

Mechanism of Growth Inhibition of Prostate Cancer Xenografts by Valproic Acid

Valproic Acid (VPA), a histone deacetylase inhibitor, has been demonstrated to cause a marked decrease in proliferation of prostate cancer (PCa) cells in vitro and a significant reduction in tumor volume in vivo. The goal of this study is to better understand the VPA-induced growth inhibition in vivo, by studying expression of various markers in PCa xenografts. Methods. For in vitro experiments, PCa cells were treated with 0, 0.6, and 1.2 mM VPA for 14 days. For in vivo models, experimental animals received 0.4% VPA in drinking water for 35 days. Tissue microarray was generated using cell pellets and excised xenografts. Results. VPA treatment causes cell cycle arrest in PCa cells in vivo, as determined by increase in p21 and p27 and decrease in cyclin D1 expression. Increased expression of cytokeratin18 was also seen in xenografts. LNCaP xenografts in treated animals had reduced androgen receptor (AR) expression. While decreased proliferation was found in vitro, increase in apoptosis was found to be the reason for decreased tumor growth in vivo. Also, an anti-angiogenic effect was observed after VPA treatment. Conclusion. VPA inhibits tumor growth by multiple mechanisms including cell cycle arrest, induction of differentiation, and inhibition of growth of tumor vasculature.

Cryoimmunotherapy in Urologic Oncology

Cryoablation is gaining acceptance as a primary treatment of localized as well as a salvage therapy of metastatic urologic malignancies. Anecdotal clinical reports suggest cryoablation can induce a systemic anti-tumor immune response; this phenomenon has been confirmed in animal models. To capitalize on this stimulatory effect of cryotherapy for control of advanced malignancies, it must be further intensified. This article reviews the existing evidence regarding cryoimmunology and discusses the mechanisms for generation of an anti-tumor immune response. Several immunotherapy approaches that can be combined with cryoablation to devise a cryoimmunotherapeutic strategy with potential to affect the progression of metastatic disease are described.

Tumor contact with prostate capsule on magnetic resonance imaging: A potential biomarker for staging and prognosis.

BACKGROUND The high-spatial resolution of multiparametric magnetic resonance imaging (mpMRI) has improved the detection of clinically significant prostate cancer. mpMRI characteristics (extraprostatic extension [EPE], number of lesions, etc.) may predict final pathological findings (positive lymph node [pLN] and pathological ECE [pECE]) and biochemical recurrence (BCR). Tumor contact length (TCL) on MRI, defined as the length of a lesion in contact with the prostatic capsule, is a novel marker with promising early results. We aimed to evaluate TCL as a predictor of +pathological EPE (+pEPE),+pathological LN (+pLN), and BCR in patients undergoing robotic-assisted laparoscopic radical prostatectomy. MATERIALS AND METHODS A review was performed of a prospectively maintained single-institution database of men with prostate cancer who underwent prostate mpMRI followed by robotic-assisted laparoscopic radical prostatectomy without prior therapy from 2007 to 2015. TCL was measured using T2-weighted magnetic resonance images. Logistic and Cox regression analysis were used to assess associations of clinical, imaging, and histopathological variables with pEPE, pLN, and BCR. Receiver operating characteristic curves were used to characterize and compare TCL performance with Partin tables. RESULTS There were 87/379 (23.0%)+pEPE, 18/384 (4.7%)+pLN, and 33/371 (8.9%) BCR patients. Patients with adverse pathology/oncologic outcomes had longer TCL compared to those without adverse outcomes (+pEPE: 19.8 vs. 10.1mm, P<0.0001,+pLN: 38.0 vs. 11.7mm, P<0.0001, and BCR: 19.2 vs. 11.2mm, P = 0.001). On multivariate analysis, TCL remained a predictor of+pEPE (odds ratio: 1.04, P = 0.001),+pLN (odds ratio: 1.07, P<0.0001), and BCR (hazard ratio: 1.03, P = 0.02). TCL thresholds for predicting+pEPE and+pLN were 12.5 and 19.7mm, respectively. TCL alone was found to have good predictive ability for+pEPE and+PLN (pEPE:TCLAUC: 0.71 vs. PartinAUC: 0.66, P = 0.21; pLN:TCLAUC: 0.77 vs. PartinAUC: 0.88, P = 0.04). CONCLUSION We demonstrate that TCL is an independent predictor of+pEPE, +pLN, and BCR. If validated, this imaging biomarker may facilitate and inform patient counseling and decision-making.

The significance of anterior prostate lesions on multiparametric magnetic resonance imaging in African-American men

INTRODUCTION African-American (AA) men tend to harbor high-risk prostate cancer (PCa) and exhibit worse outcomes when compared to other groups. It has been postulated that AA men may harbor more anterior prostate lesions (APLs) that are undersampled by the standard transrectal ultrasound guided-biopsy (SBx), potentially resulting in greater degree of Gleason score (GS) upgrading at radical prostatectomy. We aimed to evaluate the detection rate of anterior PCa significance of APLs in AA men on multiparametric magnetic resonance imaging (mpMRI) and compare it to a matched cohort of White/Other (W/O) men. MATERIALS AND METHODS A review of 1,267 men who had an mpMRI with suspicious prostate lesions and who underwent magnetic resonance transrectal ultrasound fusion-guided biopsy (FBx) with concurrent SBx in the same biopsy session was performed. All AA men were matched to a control group of W/O using a 1:1 propensity score-matching algorithm with age, prostate-specific antigen, and prostate volume as matching variables. Logistic regression analysis was used to determine predictors of APLs in AA men. RESULTS Of the 195 AA men who underwent mpMRI, 93 (47.7%) men had a total of 109 APLs. Prior negative SBx was associated with the presence of APLs in AA men (Odds ratio = 1.81; 95% CI: 1.03-3.20; P = 0.04). On multivariate logistic regression analysis, smaller prostate (P = 0.001) and rising prostate-specific antigen (P = 0.007) were independent predictors of cancer-positive APLs in AA men. Comparative analysis of AA (93/195, 47.7%) vs. W/O (100/194, 52%) showed no difference in the rates of APLs (P = 0.44) or in cancer detection rate within those lesions or the distribution of GS within those cancers (P = 0.63) despite an overall higher cancer detection rate in AA men (AA: 124/195 [63.6%] vs. W/O: 97/194 [50.0%], P = 0.007). In cases where APLs were positive for PCa on FBx, the GS of APL was equal to the highest GS of the entire gland in 82.9% (29/35) and 90.9% (30/33) of the time in AA and W/O men, respectively. CONCLUSION Cancer-positive APLs represented the highest risk GS in most cases. AA men with prior negative SBx are twice as likely to harbor a concerning APL. In our cohort, AA and W/O men had comparable rates of APLs on mpMRI. Thus, differences in APLs do not explain the higher risk of AA men for deahth due to PCa. However, targeting of APLs via FBx can clinically improve PCa risk stratification and guide appropriate treatment options.