UAB Med Cast is an ongoing medical education podcast. The UAB Division of Continuing Education designates that each episode of this enduring material is worth a maximum of 0.25 AMA PRA Category 1 credit. To collect credit, please visit UAB medicine.org/medcast and complete the episode’s post-test.

Welcome to UAB Med Cast, a continuing education podcast for medical professionals. Bringing knowledge to your world. Here's Melanie Cole.

Melanie: Welcome to UAB Med Cast. I'm Melanie Cole. And today, we're discussing testicular cancer. Joining me is Dr. Chas Peyton. He's a urologic oncologist and Assistant Professor at UAB Medicine. Dr. Peyton, it's a pleasure to have you join us today. So tell us a little bit about the incidence and demographics of testicular cancer and what have you been seeing in the trends.

Dr Chas Peyton: Well, thanks so much for the invitation to discuss this today. Testicular cancer fits into a broader category of what we call germ cell tumors of which 90% of germ cell tumors arise from the testicle. The remaining 10% arise from the mediastinum or the retroperitonium. And most testicular tumors are derived from what we call intratubular germ cell neoplasia of fetal gonocytes that don't undergo normal differentiation.

Testicular cancers are sporadic and relatively rare. And they account for about less than 1% of all tumors in men. However, it's definitely the most common solid tumor diagnosis in men ages 20 to 34. Thus, it's a critical tumor to kind of know about in men this age who usually don't have other ailments.

In 2020, it was estimated about 9,600 cases of testicular cancer of which 440 men died from their disease. The overall survival of testicular cancer ranges from about 95 to 97%. So it's a very curable disease, which is why it's important for men to know about it. However, this is remarkably improved from the 1970s where five-year overall survival was approximately 80% to 83%. A lot of this improvement has to do with the development and use of cisplatin-based chemotherapy.

Melanie: So interesting, really, the advances that we've noticed in the last, as you say, 20 years. Tell us about risk factors since this is relatively uncommon. Tell us a little bit about who might be at risk and then also what are the presenting symptoms. What would a man notice? And would he be the first one to notice something going on or might it be a provider or how does this work?

Dr Chas Peyton: So there are a few things that put men at risk for testicular cancer. One is an undescended testicle or what's known as cryptorchidism. That has four-fold increase in the relative risk of developing testicular cancer over a lifetime. Additionally, men that have a delayed orchidopexy or when the testes is brought back down into the scrotum, that's also a risk factor.

There's also epidemiologic associations between low birth weight, gestational age and twinning. They actually are also risk factors, but not nearly significant as undescended testicle. But one of the most important risk factors you have to know is that a man who has a prior germ cell tumor in one testicle or elsewhere in their body is at risk of having another germ cell tumor much more than standard population with no history of testicular or a germ cell tumor.

In terms of family history, risk between brothers that have had testicular cancer is about eight to ten times higher than the general population. And the risk between a father to son is about four to six-fold increase compared to the general population.

In terms of symptoms, the classic symptom is a painless testicular mass. Occasionally, we'll see a reactive hydrocele as part of this, but painful masses are more likely to be infection or trauma. So, painless, palpable testicular mass is always a testicular cancer until you prove it's not.

With advanced disease and metastatic disease, you can see signs of increased abdominal girth, belly or back pain, early satiation, obstructive uropathy, weight loss, anorexia, fatigue, palpable abdominal masses, supraclavicular lymphadenopathy, shortness of breath. And in rare cases, you can have hemoptysis with multiple lung metastases and then neurologic symptoms in patients with brain metastases.

Melanie: So interesting. So then doctor, tell us a little bit, if this mass is found on an exam, what's the next step? What are the recommended imaging modalities and some valuable prognostic tools that can aid you in your diagnosis?

Dr Chas Peyton: Sure. The minute someone notices a painless particular mass, or in general testicular mass at all, a scrotal ultrasound is the starting point. A scrotal ultrasound is 92% to 98% sensitive and about 95% specific. If you confirm a solid mass in the testicle, immediate referral to a urologist is what you need to do. Never order a biopsy of the testicle. We don't biopsy the testicle through the scrotum ever.

The additional workup that's needed when a testicular mass is found is serum tumor markers. And the blood serum tumor markers you obtain is beta hCG, an alpha-fetoprotein level and a lactase dehydrogenase level. You order these before you perform the orchiectomy.

Additionally, it's often recommended to go ahead and stage the patient with a CT with contrast of the abdomen and pelvis prior to the orchiectomy and a chest x-ray. However, if certain tumor markers are elevated, I'd recommend getting a CT scan of the chest.

Melanie: Well, then doctor explain testicular cancer staging after orchiectomy. What are the components and why is this so important?

Dr Chas Peyton: Right. So the critical in testis cancer is staging. And the primary way you stage them is removal of the testicle. So anyone with a solid testicular mass, you have to remove it. Urologist does it through an inguinal incision, and then you can completely stage the patient once you have the testicle in your hand. And we can look at it under the microscope and we can get the imaging that I just mentioned.

Of note, in terms of diagnosis and workup, often in the community people order PET scans, which are really not indicated. CT PET scans are only useful in very specific situations that we could talk about some other time. But to stage somebody accurately, you perform the radical orchiectomy through an inguinal incision, not through a scrotal incision. You don't biopsy the scrotum and you don't perform an orchiectomy through the scrotum, because it can disrupt lymphatic channels and spread the tumor potentially to other places where it usually doesn't go.

In terms of staging, we have clinical staging, according to the AJCC TNM staging system that's done after orchiectomy. The T is the primary tumor, which goes from 1 to 4 and 4 invades the scrotal skin. The N is the nodal stage and that's based on the retroperitoneal nodes, that is considered the regional lymph nodes for the testicle and that's based on size and number. And then the M status is based on distant metastases, either pulmonary and non-regional versus non-pulmonary and non-regional.

Lastly, in testis cancer, unlike other cancers, we have an S stage. And the S stage is a serum tumor marker level. After you remove the testicle, you wait a certain amount of time and you repeat the tumor markers and then you have an overall clinical stage picture once the tumor markers have come down. They usually have a half-life of about five to seven days, depending on which one.

There's one additional staging component that begins right before initiation in chemotherapy if this is advanced disease. And then we qualify patients into good, intermediate and poor risk for more advanced disease. If surgery is indicated, meaning removing the lymph nodes in the abdomen or removing other sites of disease, you have a final pathologic staging, which can provide the most information after you remove the testicle, they've gotten chemotherapy or not gotten chemotherapy in some situations. And then you perform what's called a primary or post-chemotherapy retroperitoneal lymph node dissection. That's when we'll have the most information as far as survival probabilities and predictive outcomes and whatnot once they're pathologically stage and surgically complete. But not all patients make it to that stage for various reasons, either they get cured or other things.

Melanie: Well, then speak a little bit to other providers about the emotional aspect of this type of cancer and how it affects men emotionally and what kind of help there is for that.

Dr Chas Peyton: Well, April is Testicular Cancer Awareness month. So you'll see lots of things on the internet. I think we have an excellent support system at UAB and there's great websites out there. The most notable one for testicular cancer support is testicularcancersociety.org.

In terms of men, these are young men that are getting a bad diagnosis and it's very tough. The other thing that's critical to understand, and I haven't mentioned much about, is that fertility's a huge deal for men in this age group that have testicular cancer. You can remove a man's testicle and they don't lose any fertility if they had normal fertility beforehand. But once you start giving chemotherapy for more advanced disease and doing these big operations, like retroperitoneal lymph nodes dissection, there's severe implications or really important implications of fertility. So that's a big stressor for men. I've had multiple patients that are completely infertile now after the testicular cancer. So that's a big deal.

The other thing to know is that men in this age group, if they get this diagnosis, in certain social situations, they're notorious for not following up appropriately. They're busy. They feel healthy otherwise. They keep on moving along in their life and that's when they get in trouble. They don't follow up and don't adhere to the cookbook recipe for testicular cancer, because like I told you, this disease is almost 95, 96, 97% curable, but you got to stick to the cookbooks. So that's really important. And what I mean by cookbooks is like the designated guidelines that are important to stick by when you're managing this disease. You won't achieve that cure rate if you don't do what the guidelines say, basically.

So it's really important to provide some emotional support and family support and really characterize the patient in terms of how they're going to respond to the treatment you're telling them. And sometimes that actually influences us in what we're going to do. But if I don't think a patient's going to show back up ever again after I see them, I may treat them a little differently to give them a slight advantage in their followup versus someone I know is reliable. So there's a lot of nuance medicine and social support that's involved with these men because they're so young when they get this diagnosis usually.

Melanie: There certainly is. And what great points that you've made for other providers. As we wrap up, Dr. Peyton, tell us any new exciting game-changers in the detection or treatment of testicular cancer. Looking forward to the next 10 years, what do you see or hope is going to happen in your field?

Dr Chas Peyton: Right. Well, the most exciting thing in testicular cancer right now is a new serum tumor marker called microRNA, and there's a bunch of trials going on right now. And this is going to be a way more sensitive and specific serum tumor marker to tell us and guide us how to move through the treatment patterns.

For example, in a lot of situations, once men have gotten chemotherapy for big masses in their abdomen from testicular cancer, we will remove those masses, but up to 40% of the time we remove those masses, but there's fibrosis, there's no tumor left. So we will have done an operation, it's a big operation and not really taken out any residual tumor because the chemotherapy basically cured it. But we don't know that right now. MicroRNA may be able to give us a glimmer of hope in delineating in that situation, which patients need surgery and which ones don't. So that's very exciting.

The other thing is, as we've advanced surgically over the years, there is way more effort now to offer occasionally what's called a primary retroperitoneal lymph node dissection to patients to avoid chemotherapy. I've gotten into it, but chemotherapy has a lot of side effects as does surgery, but the side effects for chemotherapy in somebody who's 20 is long-term and they accumulate later in life.

So being able to offer upfront surgery as an option to avoid chemotherapy is becoming more and more of an option for patients. But nonetheless, chemotherapy is an absolute here to stay forever for testis cancer, because it's one of the only few solid malignancies where cisplatin-based chemotherapy can actually cure men.

And lastly, just a quick mention of robotics on the side of surgery, there's debate in the literature, but now we're minimizing surgery as much as we can. Retroperitoneal lymph node dissection, people are very weary of doing it because it's a complex operation. It will always be complex that requires a big incision and a long hospital stay.

But now with the advent of robotics, we're really getting some great ways to do this robotically through small incisions and send men home quickly and provide them that surgery option, without maybe as many issues or prolonged hospital stay as they had in the past with a big, big incision that's required for a retroperitoneal lymph node dissection.

So those are three of the things I think that are up and coming and definitely the most exciting will be this microRNA thing that pans out over the next five to 10 years.

Melanie: What an exciting and interesting time to be in your field, Dr. Peyton. Thank you so much for joining us today. A community physician can refer a patient to UAB Medicine by calling the MIST line at 1-800-UAB-MIST.

That concludes this episode of UAB Med Cast. For more information on resources available at UAB Medicine, you can always visit our website at UABmedicine.org/physician. Also remember to subscribe, rate and review this podcast and all the other UAB Medicine podcasts. I'm Melanie Cole.