Prostate Cancer Questions Answered on Surgery, Side Effects and More

A prostate cancer journey can involve plenty of questions. As part of our patient education efforts, CURE® spoke with Dr. Oliver Sartor, a medical oncologist in the Division of Medical Oncology in the Department of Oncology at the Mayo Clinic in Rochester, Minnesota as well as chair of the Genitourinary Cancer Disease Group and director of Radiopharmaceutical Clinical Trials for Mayo Clinic Comprehensive Cancer Center, to learn some answers.

Sartor, also a member of the CURE® advisory board, answered questions related to prostate cancer, including those submitted by attendees of the CURE® Educated Patient® Prostate Cancer Summit, on topics ranging from side effects to choosing a surgeon and beyond.

Are there any long-term effects patients should be aware of from both surgery and radiation for prostate cancer?

Sartor: Yes. With regard to surgery, most of the [side effects] can come relatively early, and then there's a period of healing. Occasionally, there can be problems with urethral strictures, in which scar tissue can form around the anastomotic site for surgery, and that, at times, can be a longer-term complication.

For radiation, I think, as most men would be aware, during the acute phase, there can be issues related to bowel and bladder discomfort, frequent urination, frequent bowel movements and maybe some cramping abdominal pain that typically will resolve. But longer-term with radiation, there are potential side effects. I mentioned urethral stricture, and that can occur with radiation as well. One of the things that I really worry about is long-term bleeding complications. There can be in a subset of men, maybe as many as 10%, late complications related to bleeding from the bladder or bleeding from the rectum, and in a very long-term follow-up, there's a small but statistically increased risk of secondary cancers with radiation that are not encountered with surgery. That's a small risk and only with very long-term follow-up.

Assuming there is recurrence, what sequence of treatments typically offers the best results? Is it surgery, then some form of radiation, or radiation and then surgery?

If we look at this from a surgical perspective, initially, it turns out that many of the patients who might have a PSA [prostate-specific antigen, a protein associated with the presence of prostate cancer] rise, which is going to be evidence of failure, because if you have no prostate, you should have no PSA, that if you look at these little PSA rises that we've looked with salvage radiation for a long period of time and long studies, and we know that a substantial number of patients can actually be cured with salvage radiation after surgery, but it's PSA-dependent. If you wait until the PSA is above 0.5, then the outcome is worse. The best outcomes are in that kind of 0.1 to 0.2 range. So it's an early salvage radiation that gives the best results.

Now there's some data to show that in particularly the higher risk patients, the addition of hormonal therapy to salvage radiation may provide benefit. This is not long-term. Hormonal therapy is typically short.

Now, recurrences after radiation are problematic because the treatment of the prostate itself can yield more side effects than you might have in the absence of radiation. If you do surgery, which is an approach, you're going to have relatively poor healing and a higher rate of incontinence and sexual dysfunction than if you take a patient who is naive, as compared to post-radiation. The other element is, if you do have a localized tumor, whether or not you might be able to augment that with something like brachytherapy boost, cryotherapy, or even there are newer ways of ablating the prostate with radiofrequency ablation and the like.

One of the things that I have not mentioned, but I would like to mention is increasingly, PSMA PET [scan] is playing an important role in the evaluation of these recurrent patients. One of the key questions is, where is the recurrence and the problem that we have is that PSMA PET is often negative for patients with PSAs in the 0.1 to 0.2 range. Now, in the studies, it would appear as though you don't hit about 50% detection until you get well above 0.5, at which time we know that the outcome for radiation given in the usual manner results in poor outcomes. So men often have a decision to make about whether or not to go for the early salvage, which has a higher cure rate — or, if they have a negative PSMA, should they wait? We don't have any studies that address that, but I will say that if you have a negative PSMA PET scan, it actually is a good prognostic finding for a positive response to radiation. So a negative PSMA PET translates into a better response to radiation in the post-surgical setting, and I often do like to get a PSMA PET scan, sometimes it's positive, in which case it may be helpful. If it's negative, it also gives me information.

What kinds of questions should patients be asking when choosing their surgeon?

I think that experience does make a difference, but it's not just experience. It's also current activity. Imagine for a moment that somebody had done 1,000 prostate surgeries. Well, that's certainly a good number, but then imagine that surgeon may have been recently promoted and is now in a senior administrative position because what happens to good clinicians is sometimes they get pulled into leadership positions. Well, your previously busy surgeon is now sitting in charge of the division of surgery at a major institution. Guess what? They're not in the operating room like they used to be. So, you need to assess not only the number of patients that have been operated on but also their current activities.

I'd like to see somebody who's doing a radical prostatectomy at least a couple of times a week. You want an experienced surgeon. You want somebody who's done a lot. It's generally said for robotics, you probably need at least 300 in order to kind of get your feet under you in a reasonable way. But learning curve can be different for different surgeons, but asking about the experience, asking about the outcomes, asking about what they’re doing currently and how many patients they’ve operated on in the last month, can also be informative.

What are the complications of removing the prostate by surgery after you’ve already been treated for cancer and years later it has returned?

I don't really think about the surgical issues translating into recurrent issues. I kind of keep those separate in my mind. I talked about some of the late side effects of surgery. The early side effects of surgery are going to be two-fold. In their almost entirety, then I'll come in from some of the rare events, it's going to be incontinence and it's going to be sexual dysfunction. Those are the two issues. Sexual dysfunction is a substantial issue, and even with nerve sparing, can be expected to be a problem for at least 50% of patients, sexual dysfunction is almost an expectation with surgery. Urinary Incontinence is not, longer-term it's only about 10%.

When we look at surgery, there are also issues related to bleeding, pulmonary embolism, anesthesia complications and infection that are always going to be surgical risks, but they're not large. Nevertheless, I separate the events of a cancer recurrence and the surgical risk as two separate buckets, but please be aware that both are risks: you may have surgery and it may not succeed.

You also need to understand that it's good for patients to know that there are nomograms available based on Gleason [score], T stage, PSA, number of positive biopsies, etc., that can be used to predict the probability of a positive surgery. If you have an MRI with extracapsular extension and a Gleason 9 cancer and a PSA of 22, don't believe that surgery is going to cure the majority of patients like that. It doesn't, so to understand the context and the success of surgery within the context of your particular tumor, there are nomograms. Memorial Sloan Kettering has published some good ones where you can plug in your preoperative variables and look at your postoperative outcomes. That's a pretty good way to look at it from a prognostic perspective.

What is comprehensive genomic profiling?

That's complicated. Because the way we look at genomic profiling is in a multiplicity of ways. Do we want to look at the DNA that the patient was born with? That's called germline testing, and that can be very appropriate, particularly in patients with high-risk cancers, high Gleason cancers. Do we want to look at the genomics of the tumor? And there we look at not the DNA that you're born with, but the DNA that is contained within the tumor. And that gives you another profile. Now, rarely do we do whole-genes sequencing. I'm typically looking at about 500 genes in my contemporary analysis. By the way, for germline, we're looking at about 70 to 80 genes, kind of typically.

But then there are other types of genomics. We can look at transcriptomics, we can look at the expression of genes. These are tests, and I'll cite one called Decipher in particular, [for example] that looks at the profile of the expressed genes and that can give information.

These ways of looking at tumor genomics are all true, and they could all be useful. Rarely do they influence the actual decision, although the transcriptomics can and sometimes I will look at a transcriptome, and I will look at a genome before making the decision. But most of the time I don't need that in order to make a decision. Today, [transcriptomic profiling] is not something we do on a routine basis, but in the future, it might be routine, it depends on the results of the trials.

Is next-generation sequencing the same as comprehensive genomic profiling, or is it a type of comprehensive genomic profiling?

I don't really like the term “comprehensive genomic profiling” because it means different things to different people, and sequencing depends on what you're looking at. I prefer to speak about particular assays. Are you going to look at somatic genomic testing, germline genomic testing, transcriptomic testing, and, by the way, what tests are you going to use? And you can look at a germline with two genes. You can look at a germline with 15 genes, a germline with 70 genes. Which one are you going to do? Each one is kind of a next-generation sequencing.

With newer therapies, where are we with improving death rates, or how long a patient with stage 4 prostate cancer will live if drugs stop working?

When drugs stop working in the hormone-sensitive setting, we call that castrate-resistant disease. There's a tremendous amount of activity being focused here. You know, recent FDA approvals might include the use of Pluvicto (lutetium Lu 177 vipivotide tetraxetan). … Recently reported at ESMO 2024 was the PEACE-3 study that looked at [Xtandi (enzalutamide)] plus radium-223 as compared to [Xtandi] alone, and the combination was better than [Xtandi] alone.

We know that there are a variety of ways to be able to treat the so-called castrate-resistant prostate cancer, this is where you really need an expert oncologist because it might be a PARP inhibitor, it might be immunotherapy, chemotherapy, an isotope, or a combination. All of these need to be assessed. All of these can potentially prolong survival, but the circumstances are, how shall we say it? If you failed an ADT and an ARPI, the current survival is actually less than two years when you're castrate resistant. So we need to get better at treating these types of patients.

Regarding testosterone levels and reducing PSA, should one refrain altogether from sexual activity? Would that help?

No, [they're] unrelated.

Are there any questions your patients frequently ask you that you would like to address?

I think people want to know about the probability of success with any individual recommendation. They want to know about the side effects that they may have. They want to know what type of burden the therapy itself might impose. Are they going to have to come into the clinic, if so, how often, how much blood testing, when are we going to get scans, how are we going to evaluate the effectiveness of therapy, how do we know the therapy is working, how do we know the therapy's failing?

All of those are critical questions that have to be deeply personalized to the individual actually sitting in the office with the therapy that we're giving under the circumstances of the prior history of treatment. All of these [are] put together to really lead to a very personalized discussion, and sometimes we're imperfect in those discussions, which is also important. Please don't ask your doctor to be perfect, because they are not perfect. I don't care how good they are, they're never perfect.

This transcription was edited for clarity and conciseness.

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