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Benjamin P. Saylor is associate editor of Urology Times, an Advanstar Communications publication.

However, the data did not show any benefit of a docetaxel doublet vs an ARPI doublet.

Combination therapy linked to longer OS vs ADT in veterans with mHSPC

 is compliance officer and medical director of coding and reimbursement, United Urology Group and Chesapeake Urology, in Towson, Maryland.

Jonathan Rubenstein, MD, and Mark Painter tackle a coding question for treating stones.

Clarifying CPT 52353 billing for same-side stone cases

James C. Ulchaker, MD, shares his insights on the current range of BPH therapies.

Expert discusses the promise of emerging MISTs for BPH

Winoker is the director of endourology and director of the Center for Kidney Stone Disease at Lenox Hill and an assistant professor of urology at The Zucker School of Medicine at Hofstra/Northwell in New York, New York.

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Jared S. Winoker, MD, addresses the wide range of stone burdens treated by the CVAC system for the study.

Study results show CVAC 2.0 is safe, efficacious for wide range of kidney stones

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Craig S. Niederberger, MD, a member of the Urology Times Editorial Council, is professor and head of urology at the University of Illinois, Chicago.

This story about the operating microscope and the vas has two morals.

Infertility story offers a lesson for all urologists

Dr. De La Cerda provides an overview of a patient case involving a 68 year-old male presenting with severe back pain, with an analysis of the clinical presentation, workup, and medical history.

Bone Predominant mCRPC Patient Case

Video content above is prompted by the following:

What are your initial impressions of the case?

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The FDA has accepted a Biologics License Application (BLA) seeking approval of nivolumab (Opdivo) co-formulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20), or subcutaneous nivolumab, for the treatment of patients with all previously approved solid tumor indications for nivolumab as a monotherapy, monotherapy maintenance following completion of combination therapy with nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).

Nivolumab is currently approved under several indications, including in combination with ipilimumab for the first-line treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC), in combination with cabozantinib for the first-line treatment of patients with advanced RCC, for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy, and in combination with cisplatin and gemcitabine for the first-line treatment of patients with unresectable or metastatic urothelial carcinoma.

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024.

 According to a news release from Bristol Myers Squibb,

 approval of the formulation would make it the first and only subcutaneously administered PD-1 inhibitor.

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in the news release.

 “Opdivo is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV Opdivo but with the improved convenience of an injection administered in 3 to 5 minutes rather than a 30-to-60-minute infusion.”

The BLA submission is supported by findings from the phase 3 CheckMate-67T trial (NCT04810078), in which subcutaneous nivolumab met the study’s co-primary end points by demonstrating noninferiority to intravenous (IV) nivolumab regarding time average nivolumab serum concentration over 28 days (C

; geometric mean ratio [GMR}, 2.098; 90% CI, 2.001-2.200) and minimum serum concentration at a steady state (C

Data from the study, which were presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California,

 also showed that subcutaneous nivolumab demonstrated noninferiority to IV nivolumab in the key powered secondary end point of objective response rate (ORR). Specifically, the subcutaneous arm demonstrated an ORR of 24.2% (95% CI, 19.0-30.0) per blinded independent central review (BICR), compared with 18.2% (95% CI, 13.6-23.6) in the IV arm.

The safety profile for subcutaneous nivolumab was consistent with that of the IV formulation. Among patients who received the subcutaneous formulation, 8.1% experienced injection-site reactions, with all being low-grade and transient. Deaths due to study drug toxicity occurred in 3 patients in the subcutaneous arm and 1 patient in the IV arm. Most deaths that occurred during the study were due to disease progression.

In total, the phase 3, open-label CheckMate-67T trial enrolled 495 patients with advanced or metastatic ccRCC who had received prior systemic therapy. Patients were randomly assigned 1:1 to receive 1200 mg subcutaneous nivolumab plus rHuPH20 every 4 weeks (n = 248) or to 3 mg/kg IV nivolumab every 2 weeks (n = 247) for up to 2 years of treatment or until disease progression, unacceptable toxicity, withdrawal, or death.

The co-primary pharmacokinetic end points for noninferiority testing were C

 of subcutaneous nivolumab vs IV nivolumab. The key secondary end point was ORR per BICR.

Final completion of the CheckMate-67T study is expected in January 2026.

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 7, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-Application-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

2. Bristol Myers Squibb announces updated action date by the U.S. Food and Drug Administration for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Published online and accessed May 21, 2024. https://investors.bms.com/iframes/press-releases/press-release-details/2024/Bristol-Myers-Squibb-Announces-Updated-Action-Date-by-the-U.S.-Food-and-Drug-Administration-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

3. George S, Bourlon TB, Chacon MR, et al. Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T. 

4. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Last updated March 1, 2024. Accessed May 7, 2024. https://clinicaltrials.gov/study/NCT04810078

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024. 

News

FDA accepts BLA for subcutaneous nivolumab in solid tumors

The Ibex Prostate AI-powered solution demonstrated the ability to accurately identify and grade prostate cancer in the primary diagnosis of prostate needle biopsy (PNB) specimens, according to data presented at the United States and Canadian Academy of Pathology (USCAP) annual meeting in Baltimore, Maryland.

The study was conducted through a collaboration between Ibex Medical Analytics and the University of Pittsburgh Medical Center in Pennsylvania.

In addition to Ibex Prostate, Ibex Medical Analytics offers 2 other AI-based solutions with indications in breast cancer and gastric cancer. Data on those tools were also presented at the USCAP meeting.

"[Ibex] offers an unparalleled breadth of detection capabilities going well beyond cancer and becoming an integral part of everyday clinical practice in laboratories, hospitals, and health systems globally. With these outstanding outcomes achieved in leading US health care institutions across various tissue types, amplified by very positive user feedback, our technology continues to set the standard for AI solutions in pathology, helping clinicians improve patient outcomes,” said Chaim Linhart, PhD, in a news release on the data.

 Linhart is the chief technology officer and co-founder of Ibex Medical Analytics.

Overall, data from the Ibex Prostate study showed that in pre-classifying parts with the likelihood to be benign or malignant, Ibex Prostate demonstrated an area under the curve of 0.994 (95% CI, 0.99-0.998), a negative predictive value of 97.5% (95% CI, 95.1%-98.9%), and a positive predictive value of 99.2% (95% CI, 97.8%-99.8%). In total, the AI solution marked 17.9% of parts as suspicious (medium likelihood), with 78% of those being classified as benign and 22% as malignant per the pathologist.

Further, agreement between the AI tool and the pathologists in regard to Gleason group (GG) grading was high at 90% (defined as a complete agreement or a difference of 1 GG).

The user feedback from pathologists was also positive, with a satisfaction mark of 95% in regard to Gleason scoring, 90% in perineural invasion detection, and 95% in tissue and tumor length automated measurements. Overall, participating pathologists felt that there is potential to increase diagnostic efficiency by using the AI-powered tool in a clinical setting.

In total, the investigators in the study assessed 206 cases, which were composed of 860 parts and 1159 hematoxylin and eosin (H&E)-stained slides. The H&E-stained slides were scanned at 40x magnification. PNB specimens were collected from October 2022 to February 2023 and selected at random for AI analysis and subsequent review by genitourinary (GU) pathologists.

The AI solution was used for the prospective primary diagnosis of PNBs by 4 trained GU pathologists. The slides were also reviewed by pathologists via microscopic examination. Final diagnoses were either categorized as malignant, atypical small acinar proliferation, or benign.

The investigators concluded, “We report the successful implementation of a multi-feature AI solution that automatically imparts clinically relevant diagnostic parameters regarding prostate cancer, grading, measurements, and other pathologic features. The solution demonstrated its capability to accurately detect cancer and contribute to diagnostic quality and can serve as a valuable tool for pathologists in clinical decision-making in routine pathology practice.”

1. Korentzelos D, Deebajah MM, Quiroga-Garza GM, et al. Routine use of an artificial intelligence solution for primary diagnosis of prostate biopsies in clinical practice. Presented at: United States and Canadian Academy of Pathology Annual Meeting. March 23-28, 2024. Baltimore, Maryland. Poster 110

2. Ibex presents new data from multiple studies showcasing accuracy of AI in prostate, breast and gastric cancer diagnosis. News release. Ibex Medical Analytics. March 21, 2024. Accessed March 26, 2024. https://www.prnewswire.com/news-releases/ibex-presents-new-data-from-multiple-studies-showcasing-accuracy-of-ai-in-prostate-breast-and-gastric-cancer-diagnosis-302095787.html

Ibex Prostate, an AI-powered solution, demonstrated high accuracy in identifying and grading prostate cancer in needle biopsy specimens, as presented at the USCAP annual meeting. The study, conducted with the University of Pittsburgh Medical Center, showed an area under the curve of 0.994, with high predictive values. The AI tool achieved a 90% agreement with pathologists on Gleason grading. User feedback was positive, indicating potential for increased diagnostic efficiency. The study assessed 206 cases, highlighting the AI's capability to enhance diagnostic quality in routine pathology practice.

Overall, participating pathologists felt that there is potential to increase diagnostic efficiency by using Ibex Prostate in a clinical setting. 

Ibex Prostate demonstrates diagnostic value in prostate cancer

How common is a diagnosis of de novo metastatic prostate cancer? In an interview with 

, breaks down the answer to this question and more in the wake of former President Joe Biden’s recent cancer diagnosis.

According to Weiner, while it’s uncommon for men in the US to be diagnosed at this late stage of disease, it can happen in those who have stopped screening.

He explained, “For someone who is the former president's age range, he would certainly be above the typical age range that we might recommend screening, and certainly might be above the age range where we would say someone who was screening might want to consider stopping screening. While it's not common this day and age in the US to be diagnosed with metastatic prostate cancer, it still does happen.”
Weiner is a urologist at Cedars-Sinai Medical Center in Los Angeles, California.

Adam B. Weiner, MD, discusses prognosis and treatment options for men with metastatic prostate cancer in light of President Biden's recent cancer diagnosis.

De novo metastatic prostate cancer: Understanding Biden’s prognosis and treatment

Weiner also added, “President Biden was diagnosed with de novo metastatic prostate cancer. There are a number of great options for him at this point in terms of treatment.”

Depending on a number of factors, overall survival for patients in this disease state ranges from 5 to 10 years, according to Weiner. Ultimately, though, the decision for what treatment to pursue will be made with a few considerations in mind, including the disease volume, other medical issues, and more.

1. Biden diagnosed with ‘aggressive form’ of prostate cancer. CNN. May 19, 2025. Accessed May 22, 2025. https://edition.cnn.com/2025/05/18/politics/joe-biden-prostate-cancer

A prostate cancer expert breaks down likelihood of a diagnosis of metastatic prostate cancer and touches on available treatment options.  

De novo metastatic prostate cancer: Understanding Biden’s prognosis and treatment options

 recently hosted a pair of roundtable discussions on upper tract urothelial carcinoma (UTUC). The programs, moderated by 

 professor in the Department of Urology at NYU Grossman School of Medicine and chief of the Urology Service at Bellevue Hospital Center in New York, New York, encompassed a range of topics related to UTUC, including clinical guidelines, treatment considerations, and patient cases.

This summary was generated by artificial intelligence and edited by humans for clarity.

At the outset, Murray set the stage by outlining the prevalence of UTUC, noting that it affects 1 to 2 individuals per 100,000 people in the United States, representing about 6% of all urothelial carcinoma cases. Symptoms such as hematuria and urinary obstruction were discussed, underscoring the necessity for regular risk stratification to inform treatment decisions, particularly as one-third of patients are diagnosed with low-grade tumors. The association between upper tract tumors and concurrent bladder cancer was also emphasized, revealing that up to 13% of patients may have concomitant bladder carcinoma.

The Importance of Tumor Grade and Location

The conversation touched upon the American Urological Association (AUA) guidelines for the treatment of UTUC, which categorize tumors as low or high risk. Factors influencing this stratification include tumor size, urinary cytology results, biopsy findings, and imaging characteristics from CT scans. The further subcategorization of low-risk and high-risk variations guides therapeutic options tailored to individual patient profiles. Participants noted that their clinical practices varied significantly, reflecting their interpretations and experiences regarding the incidence of low-grade disease. Many indicated that they see approximately 20% to 30% of patients diagnosed with isolated low-grade upper tract disease.

Murray emphasized that treatment choices for low-grade UTUC depend fundamentally on tumor grade and location. Traditionally, the gold standard treatment has been radical nephroureterectomy with bladder cuff excision; however, alternatives such as segmental ureterectomy, endoscopic treatments, antegrade or retrograde ablation techniques, and adjuvant intracavitary therapies are increasingly common. The roundtable attendees shared their perspectives on how the location of a tumor—whether in the renal pelvis or ureter—plays a crucial role in treatment decisions. The importance of individualized approaches was underscored, taking into account not only the tumor’s characteristics but also the patient's overall health and preferences.

In exploring treatment innovations, the conversation highlighted the approval of a reverse thermal gel formulation of mitomycin (Jelmyto), stemming from trial data such as the OLYMPUS trial. This product is indicated for patients with unifocal tumors less than 1.5 cm, demonstrating a 59% complete response rate for low-grade disease when applied after surgical interventions aimed at debulking the tumor. Murray posited using adjuvant therapies like this to "mop up" residual disease after extensive attempts at clearance, emphasizing the collaborative nature of modern oncology where clinical trials inform treatment practices.

Special attention was also given to the complexities of endoscopic management in upper tract disease. Although ureteroscopy is commonly performed, the inherent challenges of high recurrence rates necessitated frank discussions about the potential for stricture formation and the complications tied to nephroureterectomy, which include significant impacts on renal function and associated risks, such as surgical infections and blood transfusions.

During the roundtable, several patient cases were presented that illuminate the complexities of managing low-grade UTUC. The participants shared their clinical experiences and strategies in relation to these cases, sparking a thoughtful dialogue about treatment options and decision-making processes.

One case involved a patient with high-volume, low-grade disease. The presenting physician raised concerns about the potential for undetected high-grade tumors despite biopsy results indicating low-grade pathology. This scenario ignited conversations regarding the appropriateness of nephroureterectomy, with some participating advocating for immediate surgical intervention based on the patient's symptomatic presentation, including issues such as bleeding. The uncertainty inherent in low-grade diagnoses led to different opinions on whether to proceed with radical surgery or to adopt a more conservative, kidney-sparing approach, particularly in patients with solitary kidneys.

Another case included discussions about patients who were deemed too high-risk for nephroureterectomy. Here, the focus turned to endoscopic techniques and kidney-sparing methodologies, exploring the possibility of managing high-grade tumors endoscopically. Attendees highlighted the need for individualized discussions with patients about treatment options, weighing the chance of disease progression against the quality-of-life implications of more invasive procedures. Options such as segmental ureterectomy and emerging treatments, including intraluminal therapies, were raised as alternatives worth considering for select patients.

A notable case involved the use of adjuvant treatments for patients who demonstrated residual low-grade disease after an initial resection. The introduction of therapies like mitomycin gel was discussed, particularly for patients who would not be candidates for aggressive surgical approaches. This allowed for a more conservative management strategy, circumventing major surgeries while still aiming to manage the disease effectively.

Participants underscored the importance of follow-up strategies, particularly in cases where residual disease or multifocality raised concerns about recurrence. The consensus was that rigorous surveillance protocols, including regular ureteroscopy, were vital for ensuring ongoing tumor management. Timelines for follow-up and patient education on the likely frequency of procedures were emphasized as essential components of care.

As in the first program, Murray and the participants discussed the prevalence of UTUC, the role of the AUA guidelines, and the importance of risk stratification. A significant portion of the discussion was devoted to treatment modalities, where participants shared their approaches to managing patients with low-grade UTUC. The consensus emphasized the role of endoscopic resection, often utilized as the primary treatment for low-grade tumors. In certain cases, this may be followed by perioperative intravesical therapy with chemotherapeutics like BCG or mitomycin C. The discussion also touched on the feasibility and implications of kidney-sparing surgeries, emphasizing the need to carefully evaluate patients based on tumor characteristics and individual health factors.

One participant introduced a critical point regarding the rate of undergrading in biopsies, noting findings from a recent systematic review that indicated an undergrading rate of approximately 30%. This highlighted the inherent challenges in diagnosing UTUC accurately and how these ambiguities could affect treatment decisions significantly. The group acknowledged that this undergrading could lead to either overly conservative management or more aggressive treatment than necessary, stressing the importance of comprehensive evaluation and shared decision-making with patients.

Participants discussed their experiences with recurrent cases and tailored their treatment strategies accordingly. For instance, the discussion referenced specific patient cases where clinicians had to decide between nephroureterectomy and kidney-sparing approaches based on tumor location, grade, and patient comorbidities. They acknowledged the importance of weighing risks, such as potential surgical complications and renal insufficiency, especially in patients with solitary kidneys or chronic health issues.

During the discussion, the application and benefits of mitomycin gel in treating low-grade UTUC were central themes. The discussion highlighted that although traditional treatment often involves nephroureterectomy or intraluminal therapies, the introduction of mitomycin gel presents an additional, lower-risk option to manage low-grade cases without necessitating more invasive surgical interventions.

Participants noted that the National Comprehensive Cancer Network guidelines suggest the use of mitomycin as an adjuvant therapy following endoscopic tumor ablation. This recommendation stems from its effectiveness in achieving near or complete ablation of low-grade tumors and is supported by some clinical trial data. This gel can be administered intravesically after tumor resection, allowing for a localized treatment that minimizes systemic exposure and potentially reduces adverse events.

The conversation also addressed the risk of adverse events associated with mitomycin gel, including ureteral stenosis, which was noted to be around 29% in some patients. The participants discussed managing these risks through careful monitoring and consideration of individual patient factors when recommending this treatment option.

The methods of administering mitomycin gel were also discussed. The participants shared their experiences regarding the logistical aspects, such as whether to administer the gel using a retrograde or antegrade approach, and how these methods might differ based on institutional practices. Notably, there was a focus on the crucial role of ureteral access sheaths during the procedure, which facilitated the effective delivery of the gel while allowing for thorough tumor ablation.

As in the previous program, several patient cases were discussed, including a female patient who was a longstanding smoker and had low-grade upper tract disease treated with endoscopic resection. Post-treatment, she initially achieved a complete response while using mitomycin gel, remaining in remission for approximately 2 years.

However, upon follow-up, imaging revealed a new renal pelvic mass approximately 1 cm in size, which was subsequently confirmed to be low-grade urothelial cancer. This case exemplified the high risk of recurrence associated with endoscopic treatments, with the recurrence rate estimated at approximately 60% to 70%.

Another case involved a patient with a solitary kidney and chronic renal insufficiency, which raised considerations about potential nephron loss if nephroureterectomy were performed. The discussion highlighted the challenges of predicting future complications in the contralateral kidney, especially in patients with risk factors such as diabetes and hypertension. This case underscored the importance of individualized patient assessment, considering the overall health, risk factors, and preferences related to treatment strategies.

Upper tract urothelial carcinoma (UTUC) affects 1-2 per 100,000 people in the U.S., representing 6% of urothelial carcinoma cases. Discussions emphasized the importance of tumor grade, location, and individualized treatment strategies, including radical nephroureterectomy and emerging therapies like mitomycin gel. The challenges of accurate diagnosis, risk stratification, and managing recurrence were highlighted. Case discussions underscored the complexities of treatment decisions, particularly in patients with solitary kidneys or chronic health issues, emphasizing the need for personalized approaches and rigorous follow-up protocols.

A pair of roundtable discussions encompassed a range of topics related to UTUC, including clinical guidelines, treatment considerations, and patient cases.

Upper tract urothelial carcinoma: Key considerations and patient cases

The markets have certainly been a roller coaster lately. After a solid start to the year, the US markets have been upended by the will-they-or-won’t-they Trump administration tariffs, sticky inflation, and interest rates unlikely to drop significantly anytime soon. This volatility is not unexpected when a stock market setting new record highs suddenly experiences significant headwinds. Economic indicators also show signs of an economic slowdown. Unemployment has been creeping up, and new hires have been trending down. However, overall, the US economy continues to look fairly strong. Despite this, the stock markets have been jumping up and down from one day to another.

For investors, it is critical not to overreact. You need to block out the surrounding noise and follow your investment strategy in the face of volatile markets. Actions based on emotion and fear can cause you to make mistakes that can harm your long-term investment performance. In 2020, I wrote an article during another period of high volatility (the COVID-19 shutdown) and provided some insights for investing in these environments.

• Fight the impulse to sell your holdings if the markets are dropping. Selling after drops can make temporary losses permanent and difficult to recover. Although it can be difficult emotionally, sticking to your investment strategy may be healthier for your portfolio. It is important to continue monitoring your investments, but remember the long-term reasons the investment is in your portfolio. What role is it playing? If it is still a good fit, holding the investment may be the better long-term strategy.

• Remember that you are investing for the long term. Markets have always fluctuated up and down, and during your lifetime, you are likely to experience several significant declines. Investors should ignore the noise and stay disciplined in their designed investment strategy, which was created specifically to avoid these pitfalls.

• Review your risk tolerance. Risk you took on years ago may no longer make sense given your current circumstances and stage of life.

• Make sure your portfolio is well diversified. Volatile markets have a way of exposing improperly diversified portfolios.

• Rebalance your portfolio. Market volatility can skew your allocation from its original target. Certain assets will be more affected by market swings and will move outside their target allocations. Rebalance your portfolio by selling positions that have become overweight in relation to the rest of your portfolio and move the proceeds to positions that have become underweight.

• If you must trade during volatile markets, there are defensive steps you can take to protect your positions. Stop orders and stop-limit orders can help shield unrealized gains or limit potential losses on an existing position.

• Consider adding defensive assets such as cash and cash equivalents, Treasury securities, and other US government bonds. These can help stabilize a portfolio when stocks are slipping.

Additionally, if you are fortunate to have excess resources, there may be opportunities to take advantage of the down market. However, it is best to proceed with caution. If you determine you can invest in a volatile environment, the best approach is to do so over a period of time. It is impossible to tell when the markets have hit their bottom. Do not try to guess and invest everything in 1 lump sum. If markets continue to decline, you could lose a significant amount. It is better to break the investment into smaller increments. If you are wrong, you are not wrong with all the money you planned to invest. This strategy is called dollar-cost averaging (DCA). With a DCA strategy, it is best to select 1 day per week or 1 day per month to invest a smaller percentage of the total amount you plan to invest. Selecting a day and sticking to it will enable you to ignore the outside noise. If markets continue to decline, you are incrementally buying on the downslope and will be in a better position when markets recover.

1. Witz J. COVID-19 and market fluctuation: what you should do. 

 March 24, 2020. Accessed March 20, 2025. https://www.urologytimes.com/view/covid-19-and-market-fluctuation-what-you-should-do

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"If you determine you can invest in a volatile environment, the best approach is to do so over a period of time," writes Jeff Witz, CFP.

Craig S. Niederberger, MD

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