Past, Present and Future of Radical Prostatectomy

Past, Present, and Future of Radical Prostatectomy

I have the privilege of giving the surgery lecture, past, present, and future. I venture to say that radical prostatectomy is the most difficult operation that we urologists have to perform. It’s that way primarily because of the location of the prostate in the body. It’s certainly isolated. Until relatively recently, its neuro-anatomy and vascular anatomy were not well defined. It has some important next-door neighbors in terms of quality of life issues. Certainly the rectum, the bladder, the urinary control apparatus. It’s not an easy organ to operate on.

In the early days, because of that, at least nine different approaches to trying to perform a radical prostatectomy have been described. Some of them were only described once fortunately. You can see that there are a variety of different access points in trying to reach the prostate in terms of treating a prostate cancer.

The history of radical prostatectomy is really relatively recent. The first described case was in the late 1880s. Depending upon which reference you read, it’s either in 1886 or 1887. This was probably not a radical prostatectomy. That technique was really developed by Hugh Hampton Young at Johns Hopkins in 1904 where they desired the first presentation or the first description of a perineal radical prostatectomy. Then the retropubic approach was described in the mid 1940s by Millin.

This was technically a very difficult operation. Hugh Hampton Young, they said the only reason he was able to do the procedure was because he was so technically skilled at operating. Then many others, while they came and observed him, were not able to develop the procedure in their own home institution.

Prior to the 1980s–certainly we didn’t have screening tools at that point other than the digital rectal examination–only about five-year cure rates were 50% and those were clinical cure rates, not PSA based. Certainly men with more favorable digital rectal examinations did better. Screening was even recommended at that time with routine digital rectal examinations. Surgical mortality was 3%. Severe incontinence was at least 1 in 4 patients. Essentially everyone experienced erectile dysfunction.

In the late 1970s–so not so long ago; certainly within my lifetime–only about 7% of patients were actually being treated with radical prostatectomy in the setting of clinically-localized disease. That’s I think an amazing figure.

That basically changed because of anatomical studies done by Dr. Walsh and his colleagues. In the late 1970s, early 1980s, this was really the first anatomical description of the vascular anatomy of the prostate in terms of the dorsal venous complex, Santorini’s plexus, and not just how it looked in the autopsy suite, but how that information could then be translated into the operating room to develop a reproducible operation that could be done quite safely.

Then with Dr. Donker, Dr. Walsh described the neuro-anatomy of the prostate, which developed the whole era of nerve-sparing radical prostatectomy. Despite all of the hype that comes with minimally invasive approaches, these are really the studies and the application of these anatomical studies that really made prostatectomy something that’s feasible, reproducible, and very safe in our patient population. The early 1980s is really when radical prostatectomy became the mainstay of treatment for clinically-localized prostate cancer.

The subsequent developments, one can argue whether or not they’re improvements. The subsequent developments were really minimally invasive technology. The first case description of a laparoscopic radical prostatectomy was in the early 90s. This was by Schuessler and Ralph Clayman and their group. That was the first case report. It was an abstract. The surgery took about 10 hours. The patient had a prolonged hospital stay and then in their first case series the patients, again, didn’t do very well and they thought that there was certainly no advantage to open surgery and that technological advances were needed in order to make this technology certainly viable.

Those technological advances occurred and then Guilloneau and Vallancien, the same Vallancien that did the transperineal biopsies, really showed that laparoscopic prostatectomy could be done safely with reasonable patient morbidity in a timely fashion. The original description, again, is based on anatomical studies and really applying the techniques or the studies of Patrick Walsh in terms of developing this operation.

Then subsequently as we all know the laparoscopic approach was incredibly tedious. It was much more commonly-performed in Europe than it was in the United States. Robotic technology, really in early 2000, was at first applied to radical prostatectomy. Again, a procedure that has developed over time. Most surgeries are done robotically these days in the United States, again, applying the anatomical principles that were developed prior to open surgery. That’s sort of the whirlwind of how surgery has developed since really the last 100 or so years. It’s not a long history of radical prostatectomy.

These were the first results of robotic-assisted procedures. The first case was abandoned because of bleeding. Most patients had a rapid recovery. The catheter stayed in for prolonged periods of time. What I think was underappreciated in this early series both from the laparoscopic world and now the robotic world was that continence really was not very good in these early studies and certainly that’s something that I think has developed over time as we’ve become more comfortable with actually looking at a magnified anatomy of the apex of the prostate.

From the standpoint of the future and in some cases the future is now, there has been a shift in how radical prostatectomy is actually applied. In the 80s and 90s it was really reserved for patients whom you thought had favorable risk disease, patients that we would perhaps now put on active surveillance or at least monitor them for a period of time. That really has shifted. Those patients are now active surveillance patients.

Surgery has been promoted more recently in the higher risk population. Dr. Partin voiced saying that some of his younger faculty would operate on anything basically. That’s really true. Node positive disease, even bony metastatic disease these days does not put a halt to someone going to the operating room. Some of this just became experience over time. We looked at patients who had undergone radical prostatectomy in the high-risk setting. While their prostate cancer-specific mortality was about 20% at 15 years, certainly Mormon died of other causes and many men remain disease free. The concept that high-risk patients were really not good surgical candidates started to shift in the last decade or so.

Where I think that surgery is probably going to be used more and more frequently is in the very advanced setting. That is actually happening now, meaning patients who have low volume metastatic disease, whether it’s node only or oligometastatic bone disease, that a local treatment to the prostate–and I’m talking about surgery, but certainly it can be radiation therapy–should be combined in a multimodal treatment strategy to really try to cure these patients with metastatic disease.

There’s some anecdotal evidence that this may actually beneficial. Dr. Crawford in his opening comments briefly alluded to patients with metastatic disease. If they had undergone local therapy to their prostate, be it radical prostatectomy or radiation therapy, they tended to do better in terms of survival than patients who had not had their primary cancer treated. Obviously retrospective in all of the things one could complain about, those types of studies, but at least a glimmer that local therapy combined with systemic therapy may actually benefit patients, appropriately-selected patients.

This is a recent publication by Axel Heidenreich that again looked at patients with known small volume metastatic disease that basically went on hormonal therapy. Their PSA went to nondetectable and they were either treated with radical prostatectomy or no radical prostatectomy. That was done at physician discretion. It’s not a randomized trial, but they had comparable patients, similar disease features that they then followed over time. If one looks at those who underwent surgery, the time to castration resistance, the time to clinical progression, cancer-specific survival, those were all improved in the group that had undergone treatment of their primary with radical prostatectomy.

None of the patients that had surgery required other local treatment measures, meaning TUR for local growth of cancer, stents for hydronephrosis, perks, etc, whereas about 30% of those who had not undergone treatment of their primary actually required some type of surgical intervention. Again, a suggestion that a multimodal treatment strategy may benefit some of these patients, but overall survival was not changed.

The concept that I think will happen more and more frequently now and in the future is really trying to find a strategy that will eliminate disease that really is incurable by any single modality using a multimodality approach. We do that in a variety of cancers. Testis cancer is probably the most common one that we cite, but certainly in renal cell carcinoma, ovarian cancer, breast cancer. We operate on patients that have locally advanced or even small volume metastatic disease with an improved outcome compared to any single modality.

What we’re really trying to do is initially find combinations of treatments that work best. Unfortunately, waiting for survival in the radical prostatectomy or low volume metastatic disease population really is not a very reasonable endpoint.

What we’ve proposed is actually using an undetectable PSA with non-castrate levels of testosterone as sort of a screening phase II-type study to evaluate combination therapies that will result in hopefully a chance of curing some of these patients. We know that survival’s the gold standard, but certainly a phase II model to look at whether or not we even see a signal that combination therapy works.

What therapy should we test? We’ve looked at radical prostatectomy in combination with hormonal therapy, alone, which really hasn’t shown much of a benefit, so we have to have other agents and certainly there is a plethora of other agents now. You’ll hear about those later in the meeting.

The current clinical trial that we have ongoing uses ipilimumab, which is an immunotherapy. The rationale for choosing this is that it did show some response in a couple of situations that seemed to be long term. In this melanoma study there were about 15% to 20% of patients with known metastatic disease that went on to be long-term disease-free survivors, suggesting that in a select group of patients an immune agent could actually cure them in the setting, again, of metastatic disease.

Ipilimumab has been combined with bone-directed radiation therapy and in castrate-resistant prostate cancer. Overall there was no benefit, but if you looked at those patients who actually had more favorable features, there didn’t seem to be a benefit in that patient population.

The study that we’re currently doing is hormonal therapy, usually Degarelix is what we’ve chosen, with ipilimumab for a period of about six months overall treatment time and then radical prostatectomy. This is just the treatment schema. Then we stop all therapy. The patients will typically recover their testosterone levels and we’ll look at endpoint of a nondetectable PSA between 12 and 24 months as a signal that some of these patients are doing well, so a nondetectable PSA and a noncastrate level of testosterone.

In summary, this certainly isn’t for everyone. It’s going to be patient selection and how you cherry-pick your patients. It’s an evolving strategy, but we think it’s a good way to screen various treatments. Being a Memorialite, you can’t help but finish a lecture with the Willet Whitmore dilemma. Basically I think we’ve shown that certain patients don’t need treatment, so we’re not hurting patients as much as we used to. There are patients that we can cure when that is necessary. Really it’s the right operation for the right cancer and the right patient at the right time. Thank you very much.

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