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Retrospective studies in selected patients have demonstrated a survival benefit with prostatectomy or radiotherapy (RT) of the primary tumor in metastatic hormone-sensitive prostate cancer (mHSPC). However, there is currently not enough evidence to recommend RT to the primary tumor as the standard of care for patients treated with androgen deprivation therapy plus abiraterone or docetaxel for low-volume mHSPC.

Ductal prostate adenocarcinoma (DAC) is a rare, aggressive, histologic variant of prostate cancer that is treated with conventional therapies, similar to high-risk prostate adenocarcinoma (PAC).To assess the outcomes of men undergoing definitive therapy for DAC or high-risk PAC and to explore the effects of androgen deprivation therapy (ADT) in improving the outcomes of DAC.A single-center retrospective review of all patients with cT1-4/N0-1 DAC from 2005 to 2018 was performed. Those undergoing radical prostatectomy (RP) or radiotherapy (RTx) for DAC were compared with cohorts of high-risk PAC patients.Metastasis-free survival (MFS) and overall survival (OS) rates were analyzed using Kaplan-Meier and Cox regression models.A total of 228 men with DAC were identified; 163 underwent RP, 34 underwent RTx, and 31 had neoadjuvant therapy prior to RP. In this study, 163 DAC patients and 155 PAC patients undergoing RP were compared. Similarly, 34 DAC patients and 74 PAC patients undergoing RTx were compared. DAC patients undergoing RP or RTx had worse 5-yr MFS (75% vs 95% and 62% vs 93%, respectively, p 0.001) and 5-yr OS (88% vs 97% and 82% vs 100%, respectively, p 0.05) compared with PAC patients. In the 76 men who received adjuvant/salvage ADT after RP, DAC also had worse MFS and OS than PAC (p 0.01). A genomic analysis revealed that 10/11 (91%) DACs treated with ADT had intrinsic upregulation of androgen-resistant pathways. Further, none of the DAC patients (0/15) who received only neoadjuvant ADT prior to RP had any pathologic downgrading. The retrospective nature was a limitation.Men undergoing RP or RTx for DAC had worse outcomes than PAC patients, regardless of the treatment modality. Upregulation of several intrinsic resistance pathways in DAC rendered ADT less effective. Further evaluation of the underlying biology of DAC with clinical trials is needed.This study demonstrated worse outcomes among patients with ductal adenocarcinoma of the prostate than among high-grade prostate adenocarcinoma patients, regardless of the treatment modality.

In patients with metastatic renal cell carcinoma (mRCC), the timing of systemic targeted therapy in relation to cytoreductive nephrectomy (CN) is under investigation.To evaluate postoperative complications after the use of presurgical targeted therapy prior to CN.A retrospective review of all patients who underwent a CN at The University of Texas M.D. Anderson Cancer Center from 2004 to 2010 was performed. Inclusion in this study required documented evidence of mRCC, with treatment incorporating CN.Patients receiving presurgical systemic targeted therapy prior to CN were compared to those undergoing immediate CN.Complications were assessed using the modified Clavien system for a period of 12 mo postoperatively.Presurgical therapy was administered to 70 patients prior to CN (presurgical), while 103 patients had an immediate CN (immediate). A total of 232 complications occurred in 57% of patients (99 of 173). Use of presurgical systemic targeted therapy was predictive of having a complication90 d postoperatively (p=0.002) and having multiple complications (p=0.013), and it was predictive of having a wound complication (p0.001). Despite these specific complications, presurgical systemic targeted therapy was not associated with an increased overall complication risk on univariable or multivariate analysis (p=0.064 and p=0.237) and was not predictive for severe (Clavien ≥3) complications (p=0.625). This study is limited by its retrospective nature. As is inherent to any retrospective study reporting on complications, we are limited by reporting bias and the potential for misclassification of specific complications.Despite an increased risk for specific wound-related complications, overall surgical complications and the risk of severe complications (Clavien ≥3) are not greater after presurgical targeted therapy in comparison to upfront cytoreductive surgery.

Background Targeted molecular therapies (TMTs) previously have demonstrated oncologic activity in renal cell carcinoma (RCC) by reducing the size of primary tumors and metastases. Objective To assess the cytoreductive effect of TMTs on inferior vena cava tumor thrombi. Design, setting, and participants A multi-institutional database of patients treated with TMTs for RCC was reviewed. The subset with in situ level II or higher caval thrombi (above renal vein) was assessed for radiographic response in thrombus size and level. Pre- and posttreatment characteristics of this population were assessed for predictors of response in height, diameter, and level of the tumor thrombi. Measurements The main outcome measured was a change in the clinical level of tumor thrombus following TMT. We also measured radiographic responses in thrombus size and location before and after TMT. Results and limitations Twenty-five patients met the inclusion criteria. Before TMT, thrombus level was II in 18 patients (72%), III in 5 patients (20%), and IV in 2 patients (8%). The first-line therapy was sunitinib in 12 cases; alternative TMTs were administered in 13. The median duration of therapy was two cycles (range: one to six cycles). Following TMT, 7 patients (28%) had a measurable increase in thrombus height, 7 (28%) had no change, and 11 (44%) had a decrease. One patient (4%) had an increase in thrombus-level classification, 21 (84%) had stable thrombi, and in 3 (12%) the thrombus level decreased. There was only one case (4%) where the surgical approach was potentially affected by tumor thrombus regression (level IV to III). No statistically significant predictors of tumor thrombus response to TMTs were found. Limitations include the descriptive and retrospective study design. Because TMTs were initiated according to physician and/or patient preferences, and not all patients were treated in anticipation of surgery, no conclusions could be drawn regarding selection and duration of therapy. Thus it may not be appropriate to extrapolate our experience to all patients with locally advanced RCC. Although this is the largest reported experience with in situ caval tumor thrombi treated with TMT, this series lacks sufficient statistical power to assess the usefulness of TMTs adequately in tumor thrombus cytoreduction. Conclusions TMT had a minimal clinical effect on RCC tumor thrombi. Only patients treated with sunitinib had clinical thrombus regression; however, the clinical magnitude and relevance of this effect is not clear and should be investigated prospectively.

© 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved. Context Multimodal treatment for men with locally advanced prostate cancer (PCa) using neoadjuvant/adjuvant systemic therapy, surgery, and radiation therapy is being increasingly explored. There is also interest in the oncologic benefit of treating the primary tumor in the setting of metastatic PCa (mPCa). Objective To perform a review of the literature regarding the treatment of the primary tumor in the setting of mPCa. Evidence acquisition Medline, PubMed, and Scopus electronic databases were queried for English language articles from January 1990 to September 2014. Prospective and retrospective studies were included. Evidence synthesis There is no published randomized controlled trial (RCT) comparing local therapy and systemic therapy to systemic therapy alone in the treatment of mPCa. Prospective studies of men with locally advanced PCa and retrospective studies of occult node-positive PCa have consistently shown the addition of local therapy to a multimodal treatment regimen improves outcomes. Molecular and genomic evidence further suggests the primary tumor may have an active role in mPCa. Conclusions Treatment of the primary tumor in mPCa is being increasingly explored. While preclinical, translational, and retrospective evidence supports local therapy in advanced disease, further prospective studies are under way to evaluate this multimodal approach and identify the patients most likely to benefit from the inclusion of local therapy in the setting of metastatic disease. Patient summary In this review we explored preclinical and clinical evidence for treatment of the primary tumor in metastatic prostate cancer (mPCa). We found evidence to support clinical trials investigating mPCa therapy that includes local treatment of the primary tumor. Currently, treating the primary tumor in mPCa is controversial and lacks high-level evidence sufficient for routine recommendation.

There are multiple treatment options for managing patients with renal cell carcinoma (RCC), particularly for those with a small renal mass (SRM). Surgical removal is the gold standard for treatment of localized RCC, whereas energy-ablative therapies and active surveillance are reasonable options in patients with significant comorbid medical conditions. The objective of preoperative prognostic stratification is to tailor an individual’s therapy based on anticipated outcomes of a specific biologic factor. Preoperative identification of two such factors, malignancy or high-grade malignancy, would be useful when counseling a patient with a newly diagnosed SRM. An individual’s risk can be assessed based on a single variable or through integration of multiple variables and calculating risk using a nomogram. The use of nomograms in urologic oncology has been driven by the allure of providing individualized medicine and optimizing clinical decision making based on a multitude of patient-specific variables rather than by simplistic grouping according to risk level. Although these nomograms calculate a probability of an outcome based on a population, we must keep in mind that there is still a significant amount of subjective interpretation prior to obtaining the objective prediction. It is important when assessing the utility of a specific nomogram to be aware of the variability of the model to predict for an outcome when applied to an individual patient (ie, confidence score) and to determine what each individual variable in a nomogram adds to the overall predictive ability [1]. A second important consideration when assessing a nomogram for practical use is determining if the predicted outcome will truly alter clinical decision making. In other words, is this information useful, and at what probability would decisions be altered? In this edition of European Urology, Kutikov et al [2] have attempted to use their previously published standardized renal mass quantification system, RENAL nephrometry [3], in conjunction with two additional clinical variables to develop a nomogram to predict for the presence of malignancy and high-grade disease. Several groups have previously attempted to develop clinical nomograms to determine the probability of renal masses being malignant or high grade, but they have had only modest success [4,5]. First and foremost, the group from Fox Chase Cancer Center should be congratulated on the development of the RENAL nephrometry score, which, along with PADUA score and C-index, was one of the first scoring systems originally created with the intention of providing a standardized descriptive system for renal masses based on radiologic findings. The initial goal of this stratification system was to compare surgical outcomes and practice patterns across institutions. Although this system is proving useful as an anatomic descriptor, its value for use in a predictive