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Purpose: The aim of the study was to elaborate the incidence and type of skeletal involvement in a large cohort of patients with newly diagnosed prostate cancer (PCa) referred for Ga-68 PSMA-11 PET/CT staging in a single center. Methods: Study cohort included 963 consecutive patients with newly diagnosed PCa referred for Ga-68 PSMA-11 PET/CT study for staging. The incidence of bone involvement, type of bone metastases, and extent of disease were determined and correlated with the ISUP Grade Group (GG) criteria and PSA levels. Results: Bone metastases were found in 188 (19.5%) of 963 patients. Bone metastases were found in 10.7% of patients with PSA < 10 ng/dL and in 27.4% of patients with PSA > 10 ng/dL and in 6.1% of patients with GG ≤ 2/3 and in 8.9% of patients with GG 4/5. In 7.6% of the patients, skeletal involvement was extensive, while 11.9% of patients had oligometastatic disease. Osteoblastic type metastases were the most common type of bone metastases presented in 133 of the patients with malignant bone involvement (70.7%). More than half of them had only osteoblastic lesions (72 patients (38.3%)), while the other (61 patients (32.5%)) had also intramedullary and/or osteolytic type lesions. Intramedullary metastases were found in 97 patients (51.6%), while 41 (21.8%) of them were only intramedullary lesions. Osteolytic metastases were detected in 36 patients (19.2%), of which 8 were only osteolytic lesions. Conclusion: Although traditionally bone metastases of PCa are considered osteoblastic, osteolytic and intramedullary metastases are common, as identified on PET with labeled PSMA. Skeletal spread may be present also in patients with GG ≤ 2/3 and PSA < 10 ng/dL. [ABSTRACT FROM AUTHOR]

Abstract: Context: The clinical significance of positive surgical margins (PSMs) in radical prostatectomy (RP) specimens and the management of affected patients remain unclear. Objective: To address pitfalls in the pathologic interpretation of margin status; provide an update on the incidence, predictors, and long-term oncologic implications of PSMs in the era of robot-assisted laparoscopic RP (RALRP); and suggest a practical evidence-based approach to patient management. Evidence acquisition: A systematic review of the literature was performed in April 2013 using Medline/PubMed, Web of Science, and Scopus databases and the Cochrane Database of Systematic Reviews. Studies focusing on PSMs in RP pertinent to the objectives of this review were included. Particular attention was paid to publications within the last 5 yr and those concerning RALRP. Evidence synthesis: A total of 74 publications were retrieved. Standardized measures to overcome variability in the pathologic interpretation of surgical margins have recently been established by the International Society of Urological Pathology. The average rate of PSMs in contemporary RALRP series is 15% (range: 6.5–32%), which is higher in men with a more advanced pathologic stage and equivalent to the rate reported in prior open and laparoscopic prostatectomy series. The likelihood of PSMs is strongly influenced by the surgeon's experience irrespective of the surgical approach. Technical modifications using the robotic platform and the role of frozen-section analysis to reduce the margin positivity rate continue to evolve. Positive margins are associated with a twofold increased hazard of biochemical relapse, but their association with more robust clinical end points is controversial. Level 1 evidence suggests that adjuvant radiation therapy (RT) may favorably affect prostate-specific antigen recurrence rates, but whether the therapy also affects systemic progression, prostate cancer–specific mortality, and overall survival remains debatable. Conclusions: Although positive margins in prostate cancer are considered an adverse oncologic outcome, their long-term impact on survival is highly variable and largely influenced by other risk modifiers. Adjuvant RT appears to be effective, but further study is required to determine whether early salvage RT is an equivalent alternative. [Copyright &y& Elsevier]

Purpose: We evaluated the prognostic roles of metastasectomy and an established risk stratification system in patients with disease recurrence following nephrectomy for nonmetastatic renal cell carcinoma. Materials and Methods: A retrospective analysis was performed in 129 patients with localized renal cell carcinoma treated with partial or radical nephrectomy and subsequently diagnosed with disease recurrence. At recurrence a previously validated risk score based on Karnofsky performance status, interval from nephrectomy, and serum hemoglobin, calcium and lactate dehydrogenase was used to categorize patients as being at favorable, intermediate or poor risk. Survival from time of recurrence was assessed based on risk categorization and metastasectomy. Results: Median time from nephrectomy to recurrence was 16 months. The risk score was strongly associated with median survival and the 2-year survival rate, including 73 months and 81% for favorable risk, 28 months and 54% for intermediate risk, and 6 months and 11% for poor risk, respectively (log rank <0.001). Metastasectomy performed in 44 patients (34%) was found to be of clinical benefit across the various risk categories (interaction analysis p = 0.8). On multivariate analysis a better risk category and metastasectomy were each independently associated with more favorable survival (each p <0.001). When combined, they provided 6 risk categories with an estimated 2-year survival of 0% to 93%. Conclusions: The clinical course in patients with recurrent renal cell carcinoma following nephrectomy can be variable. It is independently impacted by an objectively determined risk score and whether the patient undergoes metastasectomy. [Copyright &y& Elsevier]

Purpose: The prognostic significance and optimal management of positive surgical margins following partial nephrectomy remain ill-defined. We combine data from 2 tertiary care intuitions, and report predictors of positive surgical margins and long-term oncological outcomes for patients with positive surgical margins. Materials and Methods: Clinical, pathological and followup data on 1,344 patients undergoing 1,390 partial nephrectomies for kidney cancer were analyzed. Patients with positive surgical margins on final pathology were treated expectantly. Univariate and multivariable logistic regression models were fit to determine clinicopathological features associated with positive surgical margins. The Kaplan-Meier method was used to estimate freedom from local disease recurrence and metastatic progression. Cox proportional hazards models were used to assess whether positive surgical margin predicted local recurrence or metastatic disease adjusting for tumor size, pathological stage, histological subtype and presence of a solitary kidney. Results: Positive surgical margins were documented in 77 cases (5.5%). Decreasing tumor size and presence of a solitary kidney carried a significantly higher risk of positive surgical margins. The overall 10-year probability of freedom from local disease recurrence was 93% (95% CI 89, 95) and from metastatic progression 93% (95% CI 90, 95), with no significant difference between patients with positive vs negative margins (p = 0.97 and 0.18, respectively). Positive surgical margins were not associated with an increased risk of local recurrence or metastatic disease. Conclusions: Positive surgical margins in partial nephrectomy specimens do not uniformly portend an adverse prognosis. While every effort should be taken to ensure clear margins, our data suggest that select patients with a positive surgical margin can be safely offered vigilant monitoring without compromising long-term disease-free survival. [Copyright &y& Elsevier]

Purpose: We evaluated risk factors for positive soft tissue surgical margins and the impact of soft tissue surgical margins on metastatic progression and disease specific survival in patients treated with radical cystectomy for bladder cancer. Materials and Methods: A total of 1,589 patients who underwent radical cystectomy for primary urothelial cancer at our institution were included in the study. Several variables were analyzed including gender, age, use of perioperative chemotherapy, tumor stage, tumor grade, presence of carcinoma in situ, pathological vascular invasion, bladder pathology, status of soft tissue surgical margins, lymph node status, number of lymph nodes removed and number of positive lymph nodes. End points were freedom from progression to metastases and disease specific survival. Results: Positive soft tissue surgical margins were detected in 67 patients (4.2%). Risk factors for positive soft tissue surgical margins were female gender (p = 0.04), pathological stage, vascular invasion in the radical cystectomy specimen, lymph node metastases (all p ≤0.001) and median number of positive lymph nodes (p = 0.002). In addition, nonpure transitional cell carcinoma histology (p = 0.001) was associated with positive soft tissue surgical margins. In the 5 years after cystectomy, rates of disease specific survival for the negative and positive soft tissue surgical margin groups were 72% (95% CI 69–75) and 32% (95% CI 19–54), respectively. On multivariate analysis disease specific death was associated with tumor stage, positive soft tissue surgical margins, vascular invasion, presence of positive lymph nodes, number of nodes removed and number of positive nodes. Conclusions: Risk factors for positive soft tissue surgical margins are female gender, locally advanced cancer, presence of vascular invasion and mixed histology. Patients with positive soft tissue surgical margins have poor prognosis, and positive soft tissue surgical margins were found to be independently associated with disease specific death. [Copyright &y& Elsevier]

Abstract: Objectives: To characterise the natural history of metastatic prostate cancer after radical prostatectomy (RP) in patients followed expectantly for rising prostate-specific antigen (PSA) (noncastrate metastases). Methods: Cox proportional hazards analyses were used to assess predictors of survival among 95 patients who developed clinically detectable noncastrate metastases after RP. The initial metastatic phenotype was characterised as minimal (nodal or axial skeletal involvement) or extensive (appendicular skeletal involvement or visceral metastases). Estimates of survival after diagnosis of metastases were generated with the Kaplan-Meier method. Results: Median disease-specific survival from diagnosis of noncastrate metastases was 6.6 yr (95% confidence interval [CI], 5.2, 7.9). The initial site of metastatic disease was bone, lymph node, and viscera in 63%, 36%, and 6% of patients, respectively. Thirteen patients (14%) had extensive disease at their first metastatic manifestation. Longer PSA doubling time in the rising PSA state (hazard ratio [HR] 0.8 for each month increase in doubling time; 95%CI, 0.67–0.94) and the initial metastatic phenotype (HR 0.3 for minimal vs. extensive disease; 95%CI, 0.1–0.6) were associated with improved survival. The prostatectomy Gleason score, lymph node status at RP, PSA level at diagnosis of metastases, and interval from surgery to diagnosis of metastases did not correlate with outcome. Conclusion: Men who develop noncastrate metastases after RP may have a durable survival. Favourable prognostic indicators include longer PSA doubling time preceding diagnosis of metastases and initial involvement of axial skeleton or lymph nodes. [Copyright &y& Elsevier]

OBJECTIVE To assess the clinical and pathological findings of patients treated by bilateral retroperitoneal lymph node dissection (RPLND) after chemotherapy, to identify a subset for whom modified template nodal resection might be contemplated, as bilateral RPLND is the treatment of choice in patients with residual retroperitoneal disease after chemotherapy for nonseminomatous germ-cell tumour (GCT). PATIENTS AND METHODS The medical records were reviewed of 50 consecutive patients who had RPLND after chemotherapy between 1996 and 2005. Bilateral template RPLND was performed uniformly. Extracted lymph nodes were surgically stratified into three distinct anatomical zones by two sagittal planes running in front of the aorta and the inferior vena cava. The pathological findings were correlated with the side of the primary lesion and the extent of metastatic disease before chemotherapy. RESULTS Pathological assessment of the resected lymph nodes revealed teratoma in 28 patients (56%), viable carcinoma in three (6%), and necrosis or fibrosis in 19 (38%). All clinical stage Is, IIA and IIB left-sided primary tumours followed a predictable pattern of spread constricted to a modified left-sided template. Patients with clinical stage IIC and III, or right-sided primary tumour, had a less predictable metastatic pattern, having crossover metastases to the contralateral template. CONCLUSION Bilateral RPLND should be considered as the reference standard in patients with metastatic GCT and residual retroperitoneal mass after completing chemotherapy. However, the present data suggest that a modified template dissection might be considered even after chemotherapy in patients with left-sided primary tumours and limited nodal involvement at presentation. [ABSTRACT FROM AUTHOR]

Background: The aim of the current study was to assess whether and to what extent monitoring response to treatment using prostate-specific membrane antigen (PSMA)-based positron-emitting tomography/computerized tomography (PET/CT) studies contribute clinically relevant data to routine clinical follow-up during treatment of patients with metastatic prostate cancer (PCa). Results: Fifty-two patients with metastatic PCa who underwent [68Ga]Ga-PSMA-11 PET/CT imaging and serum prostate-specific antigen (PSA) level measurements before and during treatment were investigated. Response was categorized by serum PSA dynamics according to improvement, stable disease, and disease progression and compared to change in imaging findings on pre- and post-treatment PET/CTs. McNemar's test was used to assess agreement between PET/CT- and PSA-based responses to treatment. Thirty-four patients (65.4%) had compatible biochemical- and imaging-based response to treatment. However, the imaging and biochemical responses were discrepant in 18/52 patients (34.6%). PET/CT showed progressive disease in 5/52 patients (9.6%) and improvement/stable disease in 13/52 (25%) compared to biochemical assessment results. Discrepancy between imaging and biochemical response was most prominent in biochemically stable patients (90.9%), followed by patients with biochemical progression (33.3%), and in only few (8.7%) patients with biochemical improvement. The imaging-based response was suitable for choosing subsequent treatment in 22 of 30 patients (73.3%) with longer follow-up (median time of 10.3 months (IQR 6.3–18.2)). The relevance of the imaging methodology was reflected by its ability to assess individual lesions in cases of heterogeneous lesion responses, reveal the appearance of new lesions, and identify lesions that required specific consideration, such as targeted radiotherapy. Conclusions: Results of this retrospective analysis showed that biochemical responses to treatment and [68Ga]Ga-PSMA-11 PET/CT-based responses to treatment differ in one third of metastatic PCa patients. The latter additionally enabled lesion-based and not solely patient-based analysis. Monitoring response during treatment by [68Ga]Ga-PSMA-11 PET/CT is suitable for decision-making in patient management and choice of treatment in the majority of patients. [ABSTRACT FROM AUTHOR]