Eric A. Singer

Gleason Score 6 Adenocarcinoma: Should It Be Labeled As Cancer?

Overtreatment of low-grade prostate cancer (Gleason score ≤ 6) is a recognized problem today, with systematic prostate gland sampling triggered by prostate-specific antigen (PSA) measurements.1 The extent to which overtreatment is caused by fear of death resulting from cancer, fear of litigation from undertreatment, and misaligned incentives that reimburse more for treating rather than monitoring when appropriate is not known. Nevertheless, fear of death resulting from cancer likely plays some role, and removing the label “cancer” could reduce unnecessary treatment of low-grade disease.2,3 On the other hand, undertreatment of prostate cancer and a missed opportunity for cure in those who could benefit is a real risk of relabeling a cancer as noncancer. We have decided on an alternative modification of the Gleason scoring system and herein present the arguments for and against removing the label of cancer from Gleason 6 tumors. We believe that our alternative approach may help: one, ensure that patients receive the proper counseling/treatment; two, reduce the risk of overtreatment and its associated harms; and three, improve shared decision making.

Doppler evaluation of erectile dysfunction -Part 2

Doppler evaluation in erectile dysfunction (ED) has a significant role in determining the cause of ED. The advantages of penile Doppler and pharmacologic duplex ultrasonography include objective, minimally invasive evaluation of penile hemodynamics at a relatively low cost. Arteriogenic ED may be secondary to peripheral vascular disease and diabetes, or may be seen in association with coronary artery disease. Various parameters, such as diameter of the cavernosal artery, peak systolic flow velocity, degree of arterial dilatation and acceleration time, have been suggested for the diagnosis of arteriogenic ED, but peak systolic flow velocity is the most accurate indicator of arterial disease. This second part of the review article describes the various causes of ED and the interpretation and evaluation of color flow Doppler examination in ED.

Near Infrared Fluorescence Imaging After Intravenous Indocyanine Green: Initial Clinical Experience With Open Partial Nephrectomy for Renal Cortical Tumors

OBJECTIVE To evaluate the safety of near infrared fluorescence (NIRF) of intravenously injected indocyanine green (ICG) during open partial nephrectomy, and to demonstrate the feasibility of this technology to identify the renal vasculature and distinguish renal cortical tumors from normal parenchyma. METHODS Patients undergoing open partial nephrectomy provided written informed consent for inclusion in this institutional review board-approved study. Perirenal fat was removed to allow visualization of the renal parenchyma and lesions to be excised. The patients received intravenous injections of ICG, and NIRF imaging was performed using the SPY system. Intraoperative NIRF video images were evaluated for differentiation of tumor from normal parenchyma and for renal vasculature identification. RESULTS A total of 15 patients underwent 16 open partial nephrectomies. The mean cold ischemia time was 26.6 minutes (range 20-33). All 14 malignant lesions were afluorescent or hypofluorescent compared with the surrounding normal renal parenchyma. NIRF imaging of intravenously injected ICG clearly identified the renal hilar vessels and guided selective arterial clamping in 3 patients. No adverse reactions to ICG were noted, and all surgical margins were negative on final pathologic examination. CONCLUSION The intravenous use of ICG combined with NIRF is safe during open renal surgery. This technology allows the surgeon to distinguish renal cortical tumors from normal tissue and highlights the renal vasculature, with the potential to maximize oncologic control and nephron sparing during open partial nephrectomy. Additional study is needed to determine whether this imaging technique will help improve the outcomes during open partial nephrectomy.

Targeted therapeutic strategies for the management of renal cell carcinoma.

Purpose of review This article reviews recent developments in the use of systemic targeted therapies for the treatment of advanced clear and nonclear cell renal cell carcinoma (RCC). The genetic/molecular basis of each form of RCC is discussed and current treatments and clinical trials are described. Recent findings The treatment of advanced RCC continues to be a major challenge for uro-oncologists. The rapid growth in therapeutic options has brought much needed improvements in overall and progression-free survival, although durable complete responses remain elusive. The recent identification of mutations in genes involved in chromatin remodeling will likely lead to the investigation of whether components of this critical process can also be valid therapeutic targets in clear cell RCC. Similarly, efforts to decipher the molecular mechanisms underlying nonclear cell variants of RCC are beginning to engender novel therapeutic strategies directed against these rarer forms of kidney cancer. Despite the availability of multiple treatment options, several challenges remain: selecting the best first-line or subsequent therapy for a given patient, the optimal sequencing of the various agents available, designing trials with appropriate comparison arms and endpoints, and identifying well tolerated and effective drug combinations. Summary Agents targeting the vascular endothelial growth factor and mammalian target of rapamycin pathways remain the mainstay in the management of metastatic RCC. Ongoing and future studies are expected to facilitate the development of therapeutic regimens that incorporate agents with improved tolerability and enhanced efficacy by continuing to capitalize on the strides made by basic and translational scientists in uncovering the mechanisms underlying the various forms of RCC.

Update on targeted therapies for clear cell renal cell carcinoma.

Purpose of review The article reviews the evolution of targeted therapies for clear cell renal cell carcinoma (RCC) and recent developments in the field. The vast majority of work in kidney cancer deals with clear cell RCC, which is the most common variant of this malignancy. The identification of loss of function of the von Hippel-Lindau protein as the basis for clear cell RCC, in addition to the well designed clinical trials that have ensued, provide an outstanding model for the development of mechanism-based targeted therapy in cancer. Recent findings The treatment of advanced and metastatic RCC continues to be a major challenge for uro-oncologists despite the approval of six targeted therapies over the past 5 years. This rapid growth in therapeutic options has brought much needed improvements in overall and progression-free survival, although durable complete responses are rare. However, the plurality of treatments also poses challenges in terms of selecting the best therapy for a given patient, designing trials with appropriate comparison arms and endpoints, identifying well tolerated and effective drug combinations or sequences, and determining the role of targeted therapies in the neoadjuvant and adjuvant settings. Summary Vascular endothelial growth factor and mammalian target of rapamycin-targeted therapies continue to play a critical role in the management of advanced and metastatic RCC. Ongoing research to identify novel agents continues to build upon the work done during the elucidation of the von Hippel-Lindau/clear cell RCC pathway. It is hoped that ongoing and planned studies will enable development of therapeutic regimens that will incorporate agents with improved toxicity and better efficacy as well as defining a role for a multidisciplinary approach to the management of advanced RCC.

Androgen deprivation therapy for prostate cancer

Androgen deprivation continues to play a crucial role in the treatment of advanced and metastatic prostate cancer. In the 65 years since its use was first described, urologists and medical oncologists have developed new and innovative ways to manipulate the hypothalamic–pituitary–gonadal axis with the goal of alleviating symptoms and prolonging the life of men with prostate cancer. Despite the successes that androgen deprivation therapy has brought, each method and regimen possesses unique benefits and burdens, of which the clinician and patient must be cognizant. This review discusses the first-line androgen deprivation methods and regimens presently in use with special attention paid to their side effects and the management of them, as well as the question of when to initiate androgen deprivation therapy.

Active surveillance for prostate cancer: past, present and future.

Purpose of review This article reviews recent developments in the use of active surveillance for localized prostate cancer. Recent findings The treatment of localized prostate cancer continues to be a major challenge for urologic oncologists. Screening with prostate-specific antigen has resulted in increased numbers of low-risk prostate cancers being detected. Aggressive whole-gland therapy with surgery, or radiation therapy is associated with potentially life-altering treatment-related side effects such as urinary incontinence, bowel toxicity and erectile dysfunction. The goal of active surveillance is to avoid or delay the adverse events associated with prostate cancer therapy while still allowing for curative intervention in the future, if needed. Summary Active surveillance is a reasonable treatment option for many men with low-risk, and some men with intermediate-risk, prostate cancer. Additional research is needed to determine the optimal active surveillance inclusion criteria, monitoring schedule, and treatment triggers. It is hoped that advances in prostate imaging, biomarkers, and focal therapy will foster greater use of active surveillance in appropriately selected men to optimize quality-of-life without compromising cancer outcomes.

Renal cell carcinoma: molecular biology and targeted therapy.

Purpose of review Renal cell carcinoma (RCC) continues to be the subject of vigorous clinical and translational investigation. Advances in systemic targeted therapies, new molecular pathways and immunotherapy approaches will be discussed. Recent findings Agents targeting the vascular endothelial growth factor (VEGF) and/or the mammalian target of rapamycin (mTOR) pathways continue to be the mainstay for treating metastatic RCC (mRCC). Although enhanced target specificity has improved the toxicity profile associated with newer VEGF-pathway antagonists, durable complete responses remain the exception. Identification of novel pathways/agents, as well as the optimal sequencing and combination of existing targeted agents, remain areas of active study. In addition, emerging data from early clinical trials have reinvigorated interest in immunomodulatory agents. Summary The therapeutic armamentarium available to genitourinary oncologists continues to grow, but much work remains to be done to fully realize the potential of pathway-specific targeted strategies and immune-based approaches for mRCC.

Evolving therapeutic targets in renal cell carcinoma.

Purpose of review Recent developments in the treatment of advanced renal cell carcinoma (RCC) will be discussed, with emphasis on data published over the past year. The genetics and molecular biology of the various histologic subtypes of kidney cancer will be reviewed, as these subtle yet important genomic and metabolic alterations provide the opportunity for rational drug development and personalized treatment regimens. Recent findings Additional targeted agents continue to be added to the uro-oncologists armamentarium in the fight against metastatic kidney cancer. Targeting the vascular endothelial growth factor and its receptor, or the mammalian target of rapamycin complex, remains the foundation of systemic treatment. In clear cell RCC, increased emphasis is being placed on target selectivity and affinity in a bid to diminish off-target toxicity without compromising efficacy. Combination strategies targeting multiple pathways simultaneously continue to be explored. Histology-specific protocols testing later generation and novel agents in nonclear cell RCC should be made a priority, as there is still not a single drug approved specifically for a nonclear cell indication. Summary The number of approved treatments for advanced RCC continues to grow, but additional work is needed to further delineate the optimal drug, combination of agents, or sequence best suited to each subtype of RCC.

The Surgical Approach to Multifocal Renal Cancers: Hereditary Syndromes, Ipsilateral Multifocality, and Bilateral Tumors

Although the management of sporadic renal tumors is challenging enough, dealing with those with bilateral, multifocal, and hereditary kidney cancer adds an additional level of complexity. A clinician managing this patient population must understand the hereditary syndromes and the genetic testing available. Treating physicians must be familiar with enucleative surgery, complex or multiple tumor partial nephrectomy, complex renal reconstruction, re-operative renal surgery, and active surveillance strategies. With proper management, most patients affected with bilateral, multifocal, or hereditary RCC can have a long life expectancy while maintaining adequate renal function.