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.
Around the Practice is a monthly urologic virtual tumor board featuring live case review from multidisciplinary experts, presented by Urology Times® 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.
The panelists included moderator Raoul S. Concepcion, MD, FACS; Jason M. Hafron, MD; Joelle Hamilton, MD; and Jeremy D. Handel, MD.
CONCEPCION: 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?
HAFRON: 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.
CONCEPCION: What do the literature and clinical guidelines say in terms of when to biopsy a renal mass versus proceeding straight to surgery?
HAFRON: 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.1 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.
CONCEPCION: Dr Hamilton, please discuss why it's important for urologists and medical oncologists to consider genetic testing for patients with renal masses.
HAMILTON: 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.
CONCEPCION: 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?
HANDEL: 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.
CONCEPCION: What about going after this node, especially with the patient’s history of metastatic castration-resistant prostate cancer?
HANDEL: 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.
CONCEPCION: 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?
HAFRON: 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.
CONCEPCION: Dr Handel, would it be fairly straightforward for you to go after both the node and the renal mass in the same setting?
HANDEL: 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.
CONCEPCION: 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?
HAMILTON: 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.
CONCEPCION: What about immunotherapy?
HAMILTON: 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.
CONCEPCION: 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?
HAFRON: 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.
CONCEPCION: What would be the boundaries of your retroperitoneal node dissection?
HAFRON: 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.
ABOUT THE PANELISTS
Concepcion is director of the Comprehensive Prostate Center and clinical associate professor of urology at Vanderbilt University School of Medicine, Nashville, Tennessee.
Hafron 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.
Hamilton is an oncologist with Urology Clinics of Alabama in Homewood.
Handel 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? J Urol. 2018;200(4):731-736. doi:10.1016/j.juro.2018.04.015