Adam C. Reese

Contemporary Evaluation of the National Comprehensive Cancer Network Prostate Cancer Risk Classification System

OBJECTIVE To analyze the National Comprehensive Cancer Network prostate cancer guidelines pretreatment risk groups in a contemporary series of patients treated with radical prostatectomy. METHODS We analyzed our institutional radical prostatectomy database, including all patients with clinically localized disease treated from 2000 to 2010. Using the National Comprehensive Cancer Network guidelines, the patients were classified into low-, intermediate-, or high-risk groups. The pathologic outcomes were assessed, and the biochemical recurrence (BCR)-free survival rates were calculated and compared using the log-rank test and Cox proportional hazards analysis. RESULTS A total of 12 821 men met the inclusion criteria. The pathologic and 10-year BCR-free survival rates differed significantly by risk group (low risk, 92.1%; intermediate risk, 71.0%; and high risk, 38.8%; P < .01). Among the intermediate-risk men, the 10-year BCR-free survival was significantly greater for men assigned to the intermediate-risk group by clinical stage (88.8%) than for those deemed intermediate risk by the Gleason score (73.6%) or prostate-specific antigen (PSA) level (79.5%; P = .01). Likewise, in the high-risk men, a trend was seen toward improved 5-year BCR-free survival for patients with clinical stage T3a tumors (77.8%) compared with those considered high risk because of the Gleason score (53.7%) or PSA level (41.0%; P = .13). On multivariate analysis, clinical stage, Gleason score, and PSA level were all significantly associated with BCR. CONCLUSION We observed heterogeneous outcomes among patients within the National Comprehensive Cancer Network intermediate- and high-risk groups. The BCR-free survival rates were superior for men with an advanced clinical stage compared with those with an advanced Gleason score or elevated PSA level. This within-group heterogeneity must be considered when choosing the treatment modality and predicting an individual patients prognosis.

Pathological characteristics and radiographic correlates of complex renal cysts

OBJECTIVES To characterize pathological and cancer-specific outcomes of surgically resected cystic renal tumors and to identify clinical or radiographic features associated with these outcomes. METHODS AND MATERIALS All patients at our institution who underwent radical or partial nephrectomy for complex renal cystic masses between 2004 and 2011 with available computed tomographic imaging were included. The Bosniak score was determined, as were 10 specific radiographic characteristics of renal cysts in patients with preoperative imaging available for review. These characteristics were correlated with cystic mass histopathology. Recurrence-free survival after surgery was determined. RESULTS Overall, 133 patients underwent renal surgery for complex cystic lesions, 89 (67%) of whom had malignant lesions. Malignancy risk increased with Bosniak score (P≤0.01) and presence of mural nodules (P = 0.01). Most (63%) malignancies demonstrated clear cell histology. The papillary renal cell carcinomas (25%) exhibited lower enhancement levels (P = 0.04) and were less often septated (P<0.01). Of the malignancies, 79% were low stage (pT1), and 73% were Fuhrman grade 1 or 2. Large cyst size was associated with advanced tumor stage (P = 0.05). Neither Bosniak score nor any other radiographic parameter was associated with Fuhrman grade. In 70 patients with a median follow-up of 43 months, only 1 (1.4%) developed disease recurrence. CONCLUSIONS Most cystic renal malignancies are low-stage, low-grade lesions. Papillary renal cell carcinomas account for nearly a quarter of cystic renal malignancies and have unique radiographic characteristics. Disease recurrence after surgical resection is rare. These findings suggest an indolent behavior for cystic renal tumors, and these lesions may be amenable to active surveillance.

Evidence of prostate cancer “reverse stage migration” toward more advanced disease at diagnosis: Data from the Pennsylvania Cancer Registry

PURPOSE The widespread adoption of prostate-specific antigen-based prostate cancer screening caused a stage migration toward earlier stage disease at diagnosis. We investigated whether this stage migration has persisted in a contemporary analysis of a population-based statewide cancer registry. MATERIALS AND METHODS We analyzed the Pennsylvania Cancer Registry, a statewide registry of all newly diagnosed cancers. Data were collected on prostate cancers diagnosed between 1992 and 2012. We determined age-adjusted prostate cancer incidence and mortality rates, as well as the distribution of tumor stage (localized, regional, or metastatic) at diagnosis, and assessed for changes in these variables over time using joinpoint analysis. RESULTS Between 1992 and 2012, 210,831 new cases of prostate cancer were diagnosed in Pennsylvania, and 33,948 men died of disease. Age-adjusted prostate cancer incidence rates, and specifically the incidence of localized disease, have decreased dramatically since 2007 to 2008. Due to the decreased diagnosis of localized disease, regional and metastatic tumors have made up a greater percentage of all prostate cancer diagnoses in recent years, despite a relatively stable incidence of these advanced stage tumors. CONCLUSIONS Over the past 2 decades, age-adjusted prostate cancer incidence rates in Pennsylvania have decreased, primarily because of the decreased detection of early-stage disease. There has been a corresponding shift toward more advanced disease at diagnosis. These findings may be explained by the decreased use of prostate-specific antigen-based screening, among other factors. The 2012 United States Preventative Services Task Force recommendations against prostate cancer screening may exacerbate this concerning trend, potentially resulting in an increase in prostate cancer-specific mortality.

Development and Preliminary Testing of PROGRESS: A Web-based Education Program for Prostate Cancer Survivors Transitioning from Active Treatment

PurposeThis formative research study describes the development and preliminary evaluation of a theory-guided, online multimedia psycho-educational program (PROGRESS) designed to facilitate adaptive coping among prostate cancer patients transitioning from treatment into long-term survivorship.MethodsGuided by the Cognitive-Social Health Information Processing Model (C-SHIP) and using health communications best practices, we conducted a two-phase, qualitative formative research study with early stage prostate cancer patients (n = 29) to inform the Web program development. Phase 1 included individual (n = 5) and group (n = 12) interviews to help determine intervention content and interface. Phase 2 employed iterative user/usability testing (n = 12) to finalize the intervention. Interview data were independently coded and collectively analyzed to achieve consensus.ResultsSurvivors expressed interest in action-oriented content on (1) managing treatment side effects, (2) handling body image and comorbidities related to overweight/obesity, (3) coping with emotional and communication issues, (4) tips to reduce disruptions of daily living activities, and (5) health skills training tools. Patients also desired the use of realistic and diverse survivor images.ConclusionsIncorporation of an established theoretical framework, application of multimedia intervention development best practices, and an evidence-based approach to content and format resulted in a psycho-educational tool that comprehensively addresses survivors’ needs in a tailored fashion.Implications for Cancer SurvivorsThe results suggest that an interactive Web-based multimedia program is useful for survivors if it covers the key topics of symptom control, emotional well-being, and coping skills training; this tool has the potential to be disseminated and implemented as an adjunct to routine clinical care.

Do Ultrasensitive Prostate Specific Antigen Measurements Have a Role in Predicting Long-Term Biochemical Recurrence-Free Survival in Men after Radical Prostatectomy?

PURPOSE In this study we evaluate an ultrasensitive prostate specific antigen assay in patients with prostate cancer after radical prostatectomy to predict long-term biochemical recurrence-free survival. MATERIALS AND METHODS A total of 754 men who underwent radical prostatectomy and had an undetectable prostate specific antigen after surgery (less than 0.1 ng/ml) were studied. Prostate specific antigen was measured in banked serum specimens with an ultrasensitive assay (Hybritech® PSA, Beckman Coulter Access® 2) using a cutoff of 0.01 ng/ml. Prostate specific antigen was also measured in 44 men after cystoprostatectomy who had no pathological evidence of prostate cancer with the Hybritech assay and with the Quanterix AccuPSA™ assay. RESULTS Of the 754 men 17% (131) experienced biochemical recurrence (median 4.0 years). Those men without biochemical recurrence (83%, 623) had a minimum of 5 years of followup (median 11). Prostate specific antigen was less than 0.01 ng/ml in 93.4% of men with no biochemical recurrence, whereas 30.5% of men with biochemical recurrence had a prostate specific antigen of 0.01 ng/ml or greater. On multivariate analysis postoperative prostate specific antigen at a 0.01 ng/ml cutoff, pathological stage and Gleason score, and surgical margins were significant independent predictors of biochemical recurrence risk. Kaplan-Meier estimates for mean biochemical recurrence-free survival were 15.2 years (95% CI 14.9-15.6) for prostate specific antigen less than 0.01 ng/ml and 10.0 years (95% CI 8.4-11.5) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Biochemical recurrence-free rates 11 years after surgery were 86.1% (95% CI 83.2-89.0) for prostate specific antigen less than 0.01 ng/ml and 48.9% (95% CI 37.5-60.3) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Prostate specific antigen concentrations in 44 men after cystoprostatectomy were all less than 0.03 ng/ml, with 95.4% less than 0.01 ng/ml. CONCLUSIONS In men with a serum prostate specific antigen less than 0.1 ng/ml after radical prostatectomy a tenfold lower cutoff (0.01 ng/ml) stratified biochemical recurrence-free survival and was a significant independent predictor of biochemical recurrence, as were pathological features. Prostate specific antigen concentrations in men without pathological evidence of prostate cancer suggest that a higher prostate specific antigen concentration (0.03 ng/ml) in the ultrasensitive range may be needed to define the detection threshold.

Safety of Minimally Invasive Radical Prostatectomy in Patients with Prior Abdominopelvic or Inguinal Surgery

INTRODUCTION Despite the widespread use of minimally invasive radical prostatectomy (MIRP), there remain concerns regarding its safety in patients with a history of prior abdominopelvic or inguinal surgery. METHODS A prospective database of 1165 MIRP procedures performed by a single surgeon at a high-volume tertiary care center from 2001 to 2013 was analyzed. After an initial period of transperitoneal MIRP (TP), an extraperitoneal (EP) approach was used preferentially beginning in 2005 (for both laparoscopic and robotic cases), and robotics were used preferentially beginning in 2010. Overall perioperative complications, major complications (Clavien-Dindo III or IV), and abdominal complications (e.g., ileus, bowel/organ injury, or vascular injury) were compared for patients with and without a prior surgical history. Uni- and multivariate logistic regression were used to control the impact of robotics, approach, operative time, estimated blood loss, case number, prostate weight, and primary Gleason on complications. RESULTS Three hundred patients undergoing MIRP had prior abdominopelvic or inguinal surgery (25.8%). Of these, 102 (34%) underwent TP and 198 (66%) EP MIRP. Robotics was used in 286 cases (24.6%) and pure laparoscopy in 879 (75.4%). Complications occurred in 111 patients (9.5%) from the total cohort, with major complications in 32 (2.75%) and abdominal complications in 19 (1.63%). Prior surgery was not associated with overall, major, or abdominal complications. Of the controlling factors, only increasing operative time was associated with postoperative abdominal complications (most of which were ileus) on multivariate analysis. CONCLUSIONS In this large single-surgeon series where both EP and TP approaches to MIRP are utilized, prior abdominopelvic or inguinal surgery was not associated with an increased risk of perioperative complications.

High-resolution transrectal ultrasound: pilot study of a novel technique for imaging clinically localized prostate cancer.

OBJECTIVES To determine how high-resolution transrectal ultrasound (HiTRUS) compares with conventional TRUS (LoTRUS) for the visualization of prostate cancer. METHODS AND MATERIALS Twenty-five men with known prostate cancer scheduled for radical prostatectomy were preoperatively imaged with both LoTRUS (5MHz) and HiTRUS (21MHz). Dynamic cine loops and still images for each modality were saved and subjected to blinded review by a radiologist looking for hypoechoic foci ≥ 5 mm in each sextant of the prostate. Following prostatectomy, areas of prostate cancer ≥ 5 mm on pathologic review were anatomically correlated to LoTRUS and HiTRUS findings. The accuracy of LoTRUS and HiTRUS to visualize prostate cancer in each sextant of the prostate and to identify high-grade and locally advanced disease was assessed. The McNemar test was used to compare sensitivity and specificity and paired dichotomous outcomes between imaging modalities. RESULTS Among 69 sextants with pathologically identified cancerous foci at radical prostatecomy, HiTRUS visualized 45 and missed 24, whereas LoTRUS visualized 26 and missed 43. Compared with LoTRUS, HiTRUS demonstrated improved sensitivity (65.2% vs. 37.7%) and specificity (71.6% vs. 65.4%). HiTRUSs agreement with pathologic findings was twice as high as LoTRUS (P = 0.006). HiTRUS provided a nonsignificant increase in visualization of high-grade lesions (84% vs. 60%, P = 0.11). CONCLUSIONS HiTRUS appears promising for prostate cancer imaging. Our initial experience suggests superiority to LoTRUS for the visualization of cancerous foci, and supports proceeding with a clinical trial in the biopsy setting.

Favorable Response to Neoadjuvant Chemotherapy and Radiation in a Patient With Prostatic Stromal Sarcoma

Case Report A 66-year-old African American man initially presented to his local urologist with obstructive lower urinary tract symptoms. Digital rectal examination was performed and revealed an enlarged prostate without palpable nodules. The serum prostate-specific antigen concentration was 3.5 ng/mL. A transrectal, ultrasoundguided prostate biopsy was negative for cancer. The obstructive urinary symptoms of the patient were managed with tamsulosin and finasteride, and his prostate-specific antigen remained stable over the next several years. Six years later, the patient developed acute urinary retention for which a Foley catheter was placed. A computed tomography (CT) scan of the abdomen and pelvis revealed a 9 10 8-cm prostatic mass protruding into the bladder (Fig 1). A repeat prostate biopsy was not performed. The local urologist of the patient suspected a bladder outlet obstruction from benign prostatic hyperplasia and recommended a robotic-assisted suprapubic prostatectomy. A subtotal prostatectomy was performed robotically. Pathology from this resection revealed a high-grade (grade 3 of 3) prostatic stromal sarcoma with positive surgical margins. The prostate specimen weighed 154 g. The patient was referred to our institution for additional management. Cross-sectional imaging revealed persistent prostatic enlargement but no evidence of distant disease. Because of the incompletely resected sarcoma and violation of the tumor capsule, an aggressive management strategy including neoadjuvant chemotherapy and radiation followed by radical cystoprostatectomy was recommended. The patient received two cycles of neoadjuvant ifosfamide and adriamycin followed by 50 Gy of intensity-modulated radiation therapy. Follow-up CT of the abdomen and pelvis revealed a new 4.9 4.5 5-cm solid and cystic right lower quadrant mass consistent with a peritoneal tumor implant (Fig 2). Of note, there was residual lobulated prostatic tissue that extended into the bladder base. The patient underwent radical cystoprostatectomy with intraoperative radiation therapy. A total of 10 Gy of intraoperative radiation was delivered to the pelvis. The peritoneal mass that originated from the sigmoid colon was identified and excised (Fig 3). The postoperative course of the patient was uncomplicated. Pathology from the cystoprostatectomy specimen revealed benign prostate and bladder tissue with no residual sarcoma. Pathology from the resected peritoneal mass showed an 8-cm high-grade pleomorphic sarcoma that was consistent with the primary prostatic sarcoma tumor (Fig 4). Microscopically, the tumor was hypercellular with storiform and fascicular patterns (Fig 4A). The tumor cells had spindled morphology with pleomorphic nuclei and numerous atypical mitoses (Fig 4B). Immunohistochemically, the tumor was positive for CD117 and MDM2. CD117 is typically positive in GI stromal tumors. However, staining in GI stromal tumors is typically strong and diffuse, whereas staining of the peritoneal mass was weakly and focally positive. MDM2 positivity is often used to differentiate liposarcoma from lipoma, although this marker is nonspecific and has not been studied in prostatic stromal sarcomas.

Complications of Minimally Invasive Surgery and Their Management

Minimally invasive surgery, including both traditional laparoscopic and robot-assisted laparoscopic approaches, has increasingly become the standard of care for urologic abdominal and pelvic surgery. This is a comprehensive review of the contemporary literature regarding complications of laparoscopic and robotic urologic surgery. The review highlights pertinent studies with the goal of providing the minimally invasive urologic surgeon with an up-to-date overview of general and procedure-specific complications and their management.

Multimodal Therapy in the Treatment of Prostate Sarcoma: The Johns Hopkins Experience

BACKGROUND The objective of this study was to evaluate the use of neoadjuvant chemoradiation in patients with prostate sarcoma treated at our institution and report oncological outcomes. MATERIALS AND METHODS The records of patients with intermediate- or high-grade prostate sarcoma treated with curative intent at our institution from 1993 to 2013 were reviewed. Patient demographic information, tumor characteristics, and treatment modalities used were assessed. Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were calculated. RESULTS Eight patients met inclusion criteria. The mean age at presentation was 64 years, and urinary obstruction was the most common presenting symptom. All patients underwent surgical resection and neoadjuvant radiation and 6 had concurrent chemotherapy. Four patients received intraoperative radiation. With a median follow-up of 36 months, there were no local recurrences, 6 metastases, 4 deaths from disease, and no deaths from other causes. The median OS and CSS was 67.8 months, with actuarial OS and CSS rates of 100% at 1 year, 75% at 2 years, 62.5% at 3 years, and 62.5% at 5 years. Median RFS was 14.2 months, with actuarial RFS rate of 75% at 1 year, 37.5% at 2 years, and 25% at 3 years. CONCLUSION Prostate sarcomas are rarely cured using surgical resection alone. Our cohort treated with a multimodality approach had favorable CSS and RFS compared with historic and contemporary series of surgery alone and no local recurrences. Most patients developed metastatic recurrence, highlighting the aggressive nature of this disease.