Raoul S. Concepcion, MD

Brian, you mentioned this earlier. Let’s take the situation where this happens, and sometimes we’re trying to find disease in the patients we’re worried about. If the bone CT is negative, but let’s say you had a molecular scan that was positive, let’s say you got a fluciclovine that’s positive, and…remember, this was a patient who got external beam [radiation and] refused androgen deprivation therapy [ADT]. Let’s say it showed a 1.5-cm node above the field of radiotherapy and was seen on molecular imaging. How do you look at that patient now? What are the options that open up to you in that setting?

 I think it sounds like that would be a low-burden tumor recurrence, if indeed it’s 1 node that’s positive. I think some of the data are still somewhat emerging and still somewhat controversial, but it certainly depends on what level that node is, if it’s M0 [no metastasis detected] in the pelvis, or it’s M1, above the bifurcation. If it is M1, I think you can still go after it, or even M0 in the pelvis, [you can still] go after it. I think certainly the options in the pelvis these days are somewhat controversial, with data emerging, but whether it’s stereotactic guided radiation to that area, or we do offer salvage lymph node dissection if appropriate. If it’s M1, I think we’re more hesitant to be as aggressive with surgery. I still think there may be a role, although [the patient] may not fare as well if it is M1 disease.

Judd, what if it was an isolated lesion that they found on molecular imaging, say, L3 vertebral body?

 ADT, stereotactic radiation…I think what’s going to happen is as these scans get used more and more in this setting, these are the clinical scenarios that we’re going to start to see, which addresses the question in the queue, this concept of oligometastatic disease, and do you still put them on ADT? Regarding isolated bone lesion L3, what are your thoughts on that?

 I think No. 1, we’d present it to our tumor board, because obviously it’s very controversial, and there’s no level 1 evidence on what to do. He’s like an old-fashioned biochemical recurrence, but now he’s not really a biochemical recurrence because he has a positive novel imaging. I think we’re going to have to come up with a stage, and something to call it, like biochemical recurrence-plus, or biochemical recurrence molecular imaging. What I’d probably do in practice, and I know Dr Ghesani’s going to kick me, but I’d probably still get a regular imaging to see if that L3 lit up on a bone scan because if it least lit up on a regular scan, he would become eligible for some clinical trials that we have going on. What I don’t know, and I would ask Brian this, let’s say if you believe that’s a positive bone scan, then he becomes hormone-sensitive M1 disease.

That means you open the door for enzalutamide or abiraterone or docetaxel, not docetaxel because he’d be low volume, but you’d at least open the door for those 3 oral agents. So, is the insurance company going to approve an expensive drug like ENZA [enzalutamide] or APA [apalutamide] in the setting of a negative bone scan, but a positive Axumin scan? I’m asking more questions than I’m answering, and the honest answer is, I’d probably have to individualize, and chances are our Duke [Cancer Center] tumor board, if that was an oligometastatic site, they’d probably end up doing some spot radiation to that. I don’t know if our medical oncology team would push for ABI [abiraterone], ENZA [enzalutamide], or APA [apalutamide] in that case.

 This scenario is already playing out in our tumor boards. I see instances like these where, and Judd, you would not be wrong in ordering the bone scan, and I’ll tell you the reason why. When we look at these scans, and if we see that on CT there is a sufficiently large focus of sclerosis that lit up on the molecular imaging side, then it also gives you an idea that a bone scan may be positive given the size of the lesion. Then, if the patient’s going to the trial, you’re going to need that bone scan as a baseline so that you can compare it for treatment response in the future. So, it would be appropriate after the fact to consider doing a bone scan.

Dr Ghesani, this is a comment from the audience. Is it helpful, and should we be better about providing—especially because these scans now are so difficult to read—are we giving you enough clinical history to assist you in adequate interpretation when you read these scans?

: Yes, I can speak for my practice, and then I can relate to the other settings where there might be some difference. In our case, not only have we seen these cases being discussed at the tumor boards before the patients come in, but even if they were not presented yet and they are coming directly for imaging, we have the electronic medical record. Whenever we read the scans, we have multiple screens and I dedicate 1 screen for my Epic [medical record system] window, which is where all the records are always open.

Even nowadays, things are such that if you open up a case for dictation, not only does your dictation window open on one screen, your images open on the other, and your Epic window automatically pulls the patient’s data, so that everything is synchronized. In my practice, all the information that we need, it’s available at my fingertips. I can see that in a private practice setting, people may be wishing for more specific information that they need to make a clinical judgment about what the background of that patient is, like the 2 cases we discussed. Knowing all that information is critical when you interpret the images.



Videos

An expert panel discusses the challenges of detecting and managing biochemical recurrence in the context of oligometastatic prostate cancer. 

Molecular Recurrence in Oligometastatic Prostate Cancer  

As we approach the 1-year mark of the COVID-19 pandemic lockdown, it is appropriate to reflect on what this historic year has taught us, perhaps not in ways we typically have read about repeatedly in many publications: how we are forced to adapt our workplaces, the role of telemedicine in patient care, and learning to handle the disruption of daily routines to meet the dynamic quarantine recommendations that remain in constant flux. Instead, I hope many readers have taken the opportunity to learn from the evolving science and gone back to review the basics of virology, immune response, and clinical trial development to gain a better understanding of this global pathogen.

Remembering our high school or college days in Biology 101, we know that a virus is probably the most efficient biological particle known: It hijacks the host cellular machinery to survive. It comes in 2 basic flavors, DNA and RNA. Coronaviruses (CoV) belong to a family of single-stranded RNA particles. This becomes crucial, given that replication takes place entirely in the cytoplasm, just like messenger RNA (mRNA), and the majority of RNA viruses do not enter the host cell’s nucleus and incorporate into the DNA. And because there tend to be more errors in translation of RNA to protein (or in this case, new virions), there is a higher mutation rate with RNA compared with DNA viruses. We are seeing that play out in real time with new infections because of mutated CoV-2 particles that are being sequenced. Our understanding of the viral replication cycle is a direct result of the technological advances made over the past 2 decades, many of which correspond to our ability to carry out next-generation sequencing (NGS) at both the genome and transcriptome.

Clinically, there has been a significant interest in trying to understand the immune response to this viral load. Why can certain individuals be infected but exhibit only minimal symptoms, whereas a recognized at-risk cohort can progress rapidly to full-blown respiratory failure, end up on a ventilator, and die? Much has been written about cytokine storm and how to mitigate to prevent pulmonary failure. My brief readings in attempts to better understand the immunopathology of this pathogen suggest that the virus and hijacked host cells can evade recognition, continue replication, and evade our body’s innate and adaptive immune response. This is very much akin to some of the immune-evading mechanisms that tumor cells develop, resulting in unregulated cell growth.

Finally, the rapid development and rollout of the SARS-CoV-2 vaccine has provided hope that we can soon possibly return to some sense of normalcy. What obviously has made this vaccine unique is that rather than depending on delivering an attenuated or killed viral strain to stimulate an immune response, using a modified mRNA-based sequence will prompt the host cells to mimic the viral protein expression and simulate the natural course of the infection with resultant neutralizing specific antibodies. This has the potential for possible long-term immunity, albeit not yet proven as the vaccine trials were not designed with that as the primary end point. There are many questions to be answered regarding immunity, long-term efficacy, safety in pregnancy, missed second dose, etc. But near-term results and the ability to prevent new symptomatic infections (the end point of the trials) have been promising.

The purpose of this missive is not to persuade the readers to become amateur virologists. Rather, by studying what is current, even though not exactly carcinogenesis, we can learn valuable lessons and translate that to our understanding of tumor growth and resistance. Many of the concepts and technologies being deployed to study SARS-CoV-2 are analogous to what we are using to learn about molecular drivers in cancer cell growth and regulation. We have discussed the ongoing educational needs for urologists to better grasp the fundamentals of genomics, sequencing, neoantigens, tumor mutation burden, promotors, hypermethylation, etc, as we drive toward this goal of precision medicine. What better way than to cross-train by studying the viral life cycle and enhancing our understanding of a disease that has and will
fundamentally change life as we know it?

 is director of the Comprehensive Prostate Center and clinical associate professor of urology at Vanderbilt University School of Medicine, Nashville, Tennessee. He is editor-in-chief of 

Articles

"I hope many readers have taken the opportunity to learn from the evolving science and gone back to review the basics of virology, immune response, and clinical trial development to gain a better understanding of this global pathogen," writes Raoul S. Concepcion, MD, FACS.

From Dr. Concepcion: Lessons learned in the COVID-19 pandemic

Urology is a specialty with long-documented workforce shortages, making advanced practice providers (APPs) particularly beneficial for assisting urologists in seeing patients, obtaining histories, and even providing BCG instillations for patients with cancer. In this interview, 

, shares how her career path brought her to urology, the numerous ways she supports a urology department, and how others may pursue a similar professional focus. Donahue is an advanced practice registered nurse in the Department of Urology at Vanderbilt University, Nashville, Tennessee. She was interviewed by 

, director of the Comprehensive Prostate Center and clinical associate professor of urology at Vanderbilt University School of Medicine.

Please explain how you ended up in urology. Did you receive specialized training after obtaining your master of science in nursing?

After graduating from Furman University [in Greenville, South Carolina], with a bachelor’s in science, I was open to any job options when I landed at Urology Associates in Nashville, Tennessee. After my initial exposure to urology, I realized this is where I wanted to spend the rest of my career practicing.

When I started my master’s, I tried my best to experience every part of medicine but ultimately found myself coming back to urology, and specifically urologic oncology. When it came time to figure out next steps and what to do with a master’s, it was obvious that a urology nurse practitioner (NP) fellowship was the best next step for me. Fortunately, I was accepted to Vanderbilt University Medical Center’s Department of Urology NP Fellowship, where I was able to receive a year of specialized training in urology.

There are multiple ways to become an APP. For NPs, one must have a bachelor’s in nursing or any bachelor of science [degree], a registered nurse license, and complete a master of science in nursing. For physician assistants (PAs), one completes a bachelor’s degree in any field and then completes a master’s program. Both tracks prepare students to [work with] patients as generalists but offer little to no specialty training unless sought out by the student. Thus, making the transition into a specialty like urology may be quite difficult.

That’s where APP fellowships have proved to be pivotal in training APPs in specialty practice to be confident and independent providers. There are only a handful of urology APP fellowships across the country, so it is not reasonable to think all APPs can be trained in that way. It is important to provide adequate onboarding and education for APPs starting a new position in a specialty. With that said, it is exciting to be a part of this growing field of urology APP fellowships.

My now-colleague Gilbert Comola [ANP, CURN], who also completed an APP fellowship in urology, is the director of the fellowship and worked with the Office of Advanced Practice to develop a comprehensive training program in urology that includes spending time with each subspecialty of urology in the outpatient setting and in the operating room, as well as providing inpatient care to primary urology patients and consults. In the fellowship, I was also given dedicated time with our physicians to learn how to perform cystoscopies. With this skill, I can perform hematuria evaluations and stent pulls, or [can] address acute concerns that may require Foley [catheter] placement under cystoscopic guidance. In the fellowship, I had required didactic work as well as attendance at weekly conferences and lectures. This correlated with what I was learning clinically and has kept me eager to continue attending these educational opportunities beyond the fellowship.

What is your current position in the Department of Urology at the Vanderbilt University School of Medicine?

I am a nurse practitioner in the Department of Urology and more specifically with our oncology team. I primarily support Joseph Smith, MD, and David Penson, MD. I have my own template every day, but when Dr Smith and Dr Penson are in clinic, I help support them by seeing patients and obtaining new patient histories, and by keeping the patient flow moving. I am also fortunate to share patients with all our urologic oncology [physicians]: Sam Chang, MD; Amy Luckenbaugh, MD; Dan Barocas, MD; and Kelvin Moses, MD. I am lucky to work with all these physicians because I can continue to learn from each of them in different ways.

My current position is all outpatient, working 5 days a week with 1 administrative day. Typically, I spend this time catching up on notes, fielding the urgent/emergent calls for my patients and my MDs, following up on results, and performing peer-to-peer consults. At this point, APPs in our clinic do not take any call.

What are your daily clinical responsibilities as they relate
to patients with genitourinary (GU) cancer?

Most of my days are seeing new, return, and postoperative patients. These visits are interspersed along with following up on labs, imaging, and managing urgent and emergent calls from my patients and the patients of the physicians I primarily work with. I also spend half a day seeing patients in our advanced prostate cancer clinic with Dr Moses as well as half a day running our BCG clinic, instilling different intravesical therapies.

What challenges has the COVID-19 pandemic lockdown created in helping your patients with cancer, and how have you overcome these?

At the start of the pandemic, the most difficult part was patients asking us whether they were at higher risk by coming to Vanderbilt versus higher risk by delaying surveillance imaging, treatments, or addressing onset signs/symptoms. At the beginning, we didn’t have answers to these questions; I don’t think anyone did. Fortunately, our team quickly learned how to adjust and appropriately guide our patients to keep them safe during the pandemic but also safely and appropriately manage their GU malignancy. Of course, this wasn’t easy. This required our team and me to learn and stay up-to-date on all the ever-changing COVID-19 data.

For every challenge during this time, I like to find the silver linings. During this pandemic, I have found patients to be more open to discuss how they are feeling physically, emotionally, and mentally about their health and diagnosis. In my (biased) opinion, [receiving a diagnosis of] a GU malignancy is one of the most vulnerable diagnoses a patient can encounter. It’s always a special moment when I see that wall come down, that wall of fear and embarrassment about having to discuss not only a malignancy but also parts of their body they may have never talked about before. I think this pandemic has shown patients and even our society that it is OK to talk with health care providers about how you are feeling both physically and emotionally. It is exciting to see this shift and it is a reminder that cancer is not just a diagnosis of their physical body but also of the patient’s mental and emotional health.

Can you think of situations in which, because of your training, APPs can be better utilized to enhance quality and efficiency of care for patients with GU cancer?

Although I am a GU oncology NP, there are numerous adverse events (AEs) from the management of these malignancies that require input from other disciplines of urology, including voiding dysfunction, sexual medicine, and endourology, requiring me to have knowledge in each of these areas. Having training in all of urology during my fellowship has given me the tools and confidence to manage these issues on my own and the understanding of when to refer for a higher level of care. For example, the most common AEs of radical prostatectomy are urinary incontinence and erectile dysfunction. The fellowship allowed me to learn from our experts in each of these areas to appropriately manage patients on my own and [to gain] an understanding of when to advance the level of care for possible surgical therapies. So I can confidently manage a postprostatectomy PSA [prostate-specific antigen] but also any other urologic concerns that arise post therapy. Another benefit that I and one of my supervising physicians, Dr Smith, identified is that I am able to commit more time to management of these significant life-altering issues and formulate surveillance plans for our patients, ultimately allowing him more time for new patients, operating, or seeing our more complex patients.

Regarding managing postsurgical complications in this population, having spent time in the operating room as well as with our inpatient service has given me invaluable tools to acutely take care of patients in the possible urgent/emergent concerns in the postoperative period. It gave me awareness to know what I can manage in the outpatient versus when to admit someone for inpatient care.

Over the next 5 years, how do you think the role of the APP will evolve, given the advancement of diagnostic testing and plethora of new therapies (and indications) across the various tumor types?

It is certainly an exciting time, witnessing and being a part of the advancements in diagnostic tests as well as novel therapies in urologic oncology. APPs are and will continue to be critical in the implementation and education for patients during the advancement of new tests and therapies.

During the past few months, I have worked closely with our medical oncology team and the hereditary cancer clinic to bring germline testing into the urology clinic for [patients at high risk of prostate cancer who] qualify based on the latest NCCN [National Comprehensive Cancer Network] guidelines. As an APP, I have the time to both set up the logistics of having a new test to offer as well as the time to spend with patients educating them on germline testing in high-risk prostate cancer. There have certainly been logistic hurdles along the way with incorporating a new test into our flow of these, but I have been fortunate to work with a multidisciplinary team to make this process both easy to understand and streamlined for our patients. As we mature our process in offering genomic testing in the urology clinic, our hope is that this multidisciplinary approach can be adopted at other institutions nationwide. Across urologic oncology, there are new and developing testing and therapies, including prostate-specific membrane antigen scanning, blue light cystoscopy, and novel intravesical treatments. With these complex advances comes the increasing need for a team-based approach in the care of our patients. The APP plays a special role as a medical provider closely working with the physician in management, as the patient advocate, and as a liaison for the multidisciplinary approach that these advances will require us to take.

Of course, this will require APPs to stay prudent on learning these changes and updates. We have all our APPs join the American Urological Association, which has vast amounts of education, lectures, and of course guidelines. Likewise, we encourage having NCCN accounts as well as memberships in the Society of Urologic Nurses and Associates and other groups to keep ourselves educated on the quickly changing landscape of urologic oncology.

You are employed in a very highly specialized academic environment. What do you think would be the major critical pieces that independent urology groups should be considering in order to incorporate APPs into their advanced cancer care model?

APP utilization in urology is a topic that [many of my colleagues and I] are always working to improve and maximize. Before incorporating APPs into advanced cancer care, it is critical to start early with adequate education and training. As APPs, we are trained in primary care, where we learn how to medically manage patients. But making the transition to specialize and focus on a particular discipline can be a difficult task. That is where urology groups must take responsibility to provide adequate time and resources for newly hired APPs (those who did not complete a fellowship) to learn how to confidently manage the breadth of urology patients, and in this case urologic oncology patients. My APP colleagues and I have created a formal onboarding plan for newly hired APPs that requires more work on the front end but pays off when we have a new APP who can function independently.

Having worked in an independent urology group prior to becoming an NP, I have a good sense of the similarities and differences of independent groups versus academic urology. Regarding utilization of APPs, I don’t think our roles differ drastically. In independent urology groups, APPs likely work more as general providers [because] the physicians tend to see all areas of urology. If independent urology groups want to specialize their APPs into oncology roles, there are certainly efficient ways to do so.

Once you have an appropriately trained APP, the options for incorporating them into your advanced cancer care model are endless. An easy way to incorporate APPs into your model is to have the APP see the returns and [patients undergoing routine cancer surveillance]. This could be seeing patients for routine PSA monitoring or surveillance imaging and labs for patients with a history of urothelial carcinoma or renal neoplasms. This allows our MDs more time to see the new patients, the more complex patients, and even more time in the operating room. We even take advantage of this model in our advanced prostate cancer clinic. Patients [doing well on therapy whose PSA is stable], I can see … independently, draw labs, give any injections, address AEs/concerns, and send on their way, ultimately leaving Dr Moses more time with our new and more complex patients who often require extensive counseling and evaluation.

At Vanderbilt, our BCG/intravesical therapy clinic is managed by an APP. This includes not only giving patients their treatments but also managing AEs, questions, and concerns. This is an excellent way to utilize APPs, because intravesical therapies often come with a host of AEs that must be medically managed. Having an APP run an intravesical therapy clinic gives patients another provider who understands their pathology, diagnosis, and scheduled treatment plan.

A nurse practitioner discusses how she supports multiple providers in a large academic practice.

How APPs can be involved with genitourinary cancer care

Around the Practice is a monthly urologic virtual tumor board featuring live case review from multidisciplinary experts, presented by 

® in partnership with LUGPA. On January 20, 2021, a panel convened to discuss cases involving an incidentally discovered renal mass as well as upper tract transitional cell carcinoma. What follows is an edited portion of the panel’s conversation regarding the incidentally discovered renal mass case.

Raoul S. Concepcion, MD, FACS; Jason M. Hafron, MD; Joelle Hamilton, MD;

This is a 65-year-old Caucasian male who is noted to have an incidental 3-cm right renal mass, enhancing on a contrasted CT scan as part of a routine follow up for his metastatic castration-resistant prostate cancer, diagnosed in 2017 and currently undergoing therapy. He underwent a CT-guided biopsy by the local interventional radiologist, which showed atypical cellular infiltrate, favoring a primary renal neoplasm, but due to the dense amount of fibrosis and chronic inflammation, a definitive renal cell cancer could not be determined.

The patient met with his urologist and after shared decision-making, the patient opted for a repeat CT scan in 3 months rather than going directly to surgery. In December 2020, the repeat scan showed an interval enlargement of the mass from 3.1 cm to 4.6 cm and new peri-caval adenopathy, the largest being about 2.5 cm. Hounsfield units of the renal mass pre and post were 34 and 70, and 40 to 60 for the caval node.

The patient’s initial prostate cancer was Gleason 4+5 and underwent a radical prostatectomy. His final pathology was T3b and he received adjuvant radiotherapy due to a persistently elevated PSA postoperatively. In 2018, he had a rising PSA and was started on androgen deprivation therapy [ADT], and ultimately went on both ADT as well as enzalutamide [Xtandi] for metastatic castration-resistant prostate cancer (mCRPC). His current PSA is 0.03. Physical exam was unremarkable, and no cutaneous lesions were noted. Family history was significant for 'bone’ cancer, according to the patient.

Images of the tumor indicate that it is an upper pole right renal mass. Dr Hafron, what is going through your mind with this very challenging case?

 Yes, this is definitely a challenging case, especially with the history of mCRPC. I think what's critical here is the appearance of the mass. It's not a classic small renal mass; it doesn't have well-circumscribed borders. The borders are very irregular, and it looks infiltrative a little bit. I would absolutely do a biopsy, especially with the history of metastatic disease.

 What do the literature and clinical guidelines say in terms of when to biopsy a renal mass versus proceeding straight to surgery?

 I think the question is: Is the biopsy going to make a difference in your management? If a patient is not planning to have the lesion treated, is a biopsy really going to make a difference? Probably not. But if you're considering any intervention, whether it's ablative or surgical, I like to biopsy it. It's a tricky discussion to have with the patient, though, because there are a couple of nuances with biopsy.

There was a great study in Canada that looked at centers that do a lot of biopsying versus centers that don't do a lot of biopsying.

 In the centers that regularly biopsy their small renal masses, the benign surgical resection rate was significantly lower. So I think it's important to incorporate a biopsy in your evaluation of these patients, because the last thing you want to do is put a patient through a surgical resection that is not necessary.

Most tumors throughout the body are biopsied, so why would renal masses be different? But for some reason, urologists have never really gravitated towards biopsy of renal masses. But I think it's very helpful as long as you plan an intervention. If this patient was 85 years old, or his prostate cancer was leading to poor performance and I don't plan to intervene on him, I wouldn't biopsy. But if I'm planning the intervention, whether it's ablative or a surgical resection, I like to get that tissue to avoid unnecessary therapy, if possible.

Dr Hamilton, please discuss why it's important for urologists and medical oncologists to consider genetic testing for patients with renal masses.

 Just as a caveat, I should note that this patient was treated by me for prostate cancer so I have already done germline testing revealing no pathogenic mutations (specifically no VHL [Von Hippel-Lindau] syndrome). RALP performed 2017, with scans incidentally finding the renal mass.In the setting of prostate cancer progression, I would then do genomic sequencing.

When it comes to renal cancer, statistically, less than 5% of patients have a germline mutation consistent with a heritablerenal cancer syndrome. This patient does not have a family history of renal cancer, or any other cancers, suggestingVHL mutation. When a RCC familial syndrome is present with aspontaneous mutation, they tend to be in a younger patient and/orbilateral or multicentric. When it comes to genomic sequencing, at this point in time, there are no FDA-approved data that show that finding particular mutations in the active tumor itself will be more fitting for a particular treatment over another. However, clinical trials right now are trying to determine whether 1 treatment is better than another if a patient has a somatic mutation or a germline mutation.

 Dr Handel, you trained at an institution where you saw a lot of renal lesions. What are your thoughts on the challenges for this particular patient, whether it be the renal lesion or even going after the caval lesion for biopsy?

The kidney lesion and the peri-caval lesions all look amenable to biopsy. That could be done with ultrasound or CT; it comes down to operator preference. The way our group practices, if you're going out to the kidney, it would most likely be scheduled as an ultrasound-guided approach; for the caval nodes, it would almost certainly be CT guided. Most of the time, we use coaxial technique, which has dramatically reduced track seeding.

Another consideration is whether there is an area of central necrosis that we want to avoid. Sometimes that means going to the edge of the mass. On that coronal image, you can see that the image gets fairly central, so I would try to biopsy away from the center of the kidney, basically looking to avoid the larger renal artery branches to avoid a post-biopsy bleed.

Bleeding is common after renal biopsies. To avoid significant bleeds, we'll either do some prolonged ultrasound on the area to hopefully tamponade it, or we will sometimes inject helitene, which is a hemostatic gelfoam, directly through the stylet to tamponade bleeding. Angiography and embolization is the usual back-up plan for significant uncontrolled bleeding.

 What about going after this node, especially with the patient’s history of metastatic castration-resistant prostate cancer?

 These would be fairly bread-and-butter cases from our perspective. We wouldn't have a problem going after them. That would be a pretty routine CT-guided case.

 Dr Hafron, there is an upper pole mass that previously was suspicious, and there is a pair of caval nodes. Would you recommend biopsying 1 or both of these?

 I would like to get tissue from the lymph nodes around the vena cava, but I think the key with this clinical situation is a multidisciplinary approach. When dealing with stage 4 systemic disease, this is when medical oncology needs to get involved. I would work very closely with them.

However, it's clearly systemic disease, and the sequence for surgery and for targeted therapy become critical.

 Dr Handel, would it be fairly straightforward for you to go after both the node and the renal mass in the same setting?

 I don't actually get a lot of requests for that. But in this case, I think it would be very reasonable. You could pretty easily do a CT guide and get them both at the same time. That's not an unreasonable request. Interestingly, I don't seem to get a lot of requests for more than 1 site. If you do 1 and the patient is not tolerating it and you need to stop and stage it, then you just stop.

 Dr Hamilton, let's just say for the sake of discussion, the caval node is consistent with renal cell and you have this upper pole mass. Can you talk a little bit about sequencing and the role of neoadjuvant therapy in the setting of metastatic disease?

 For this patient, with a low volume of renal cancer, the options would be resection or systemic therapy. You mentioned neoadjuvant treatment, but there are no published phase 3 trials that show us data. If a patient has unresectable RCC, you could try a [vascular endothelial growth factor receptor tyrosine kinase inhibitor] such as Sutent [sunitinib] or Votrient [pazopanib]. Response rates may be in the 40% to 50% range for this. I've done this in patients who do not have resectable disease or are not candidates for an operation. The data are not very robust, but it is done because we’re treating a patient, not a guideline. I would lean towards, if remotely possible, to resect what he does have. Otherwise, if he doesn't have a resection long term, I am committing him to long-term systemic therapy. If he were to be able to have resection of lymph nodes in the renal mass, we would have a discussion about adjuvant therapy of renal cancer after resection.

When adjuvant sunitinib or sorafenib [Nexavar] is compared to placebo, there is not a survival benefit, but there is a progression-free-survival benefit. So essentially, the patient's on an oral agent for a year and on average, they have a 1-year delay of recurrence. So instead of about 5 and a half years, it's 6 and a half years. It is challenging to convince a patient to take a fairly toxic drug for a year to gain a year of disease-free survival. Normally, I would look to see what clinical trials a patient is a candidate for, but in this case, with his history of prostate cancer, he would not be a candidate for trials.

 There is a really interesting trial evaluating neoadjuvant nivolumab [Opdivo] called PROSPER (NCT03055013). That would be great for a patient who doesn't have prostate cancer.

In the setting of metasatasis, there are many options. One option is combination immunotherapy, such as nivolumab plus ipilimumab (Yervoy). There is also combination immunotherapy-tyrosine kinase inhibitor treatment with pembrolizumab [Keytruda] and axitinib [Inlyta]. There are many oncology arguments about which to choose, and sometimes what I'll do is look at the patient's comorbid conditions to see which would better align with them. I tend to favor pembrolizumab/axitinib just because the dual immunotherapy has a complete response rate of around 10%, whereas there is a better response rate with pembrolizumab/axitinib, and we are seeing markedly improved survival a couple of years out.

Dr Hafron, let's just say the biopsies come back with renal cell carcinoma and the patient decides on surgery. With the prior history of 2 biopsies inside of 3 months, does that affect your approach? Can you still do this robotically?

 For this patient, his best chance to avoid long-term systemic therapy is surgical resection. The mCRPC is a confounding factor in his life expectancy, but I would do everything to resect him. I would try to do a partial cytoreductive kidney surgery with lymphadenectomy. I’m primarily a robotic surgeon, but I don't think this is a great robotic case just because, based on the images, you're going to have to mobilize and maybe even get behind the cava. Based on my experience and comfort level, I would have vascular surgery on standby to help with the caval dissection. I would do an aggressive lymphadenectomy because this is his only real hope for cure.

 What would be the boundaries of your retroperitoneal node dissection?

 I would pretty much do a right-sided modified testicular RPLND cancer template.

The challenge here is getting posterior to the vena cava; that is why I would have vascular surgery on stand-by. The only chance for this patient is a surgical resection. Otherwise, we deem him unresectable and send him for systemic therapy for the rest of his life.

It’s a difficult discussion, especially when you're talking with a patient who already has terminal prostate cancer. Close collaboration with hematology/oncology is going to be critical.

 is director of the Comprehensive Prostate Center and clinical associate professor of urology at Vanderbilt University School of Medicine, Nashville, Tennessee.

 is a partner at the Michigan Institute of Urology, PC; an associate professor of urology at the William Beaumont School of Medicine, Oakland University; and the director of robotic surgery at Beaumont Hospital Royal Oak in Michigan.

 is an oncologist with Urology Clinics of Alabama in Homewood.

 is a vascular and interventional radiologist at Beaumont Hospital Royal Oak.

1. Richard PO, Lavallée LT, Pouliot F, et al. Is routine renal tumor biopsy associated with lower rates of benign histology following nephrectomy for small renal masses?

. 2018;200(4):731-736. doi:10.1016/j.juro.2018.04.015

An expert panel discusses the case of a 65-year-old Caucasian male who is noted to have an incidental 3-cm right renal mass, enhancing on a contrasted CT scan as part of a routine follow-up for his metastatic castration-resistant prostate cancer, diagnosed in 2017 and currently undergoing therapy.

Raoul S. Concepcion, MD

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Case review: An incidentally discovered renal mass