Authors:

Marc Beishon

Simon Crompton

Introduction

Prostate cancer is the most common cancer in men across Europe, accounting for almost one in four cancer diagnoses in males. Today, surgery to remove the prostate in its entirety is one of three treatment options for early-stage prostate cancers, and some locally advanced prostate cancers – the other options being radiotherapy and active surveillance. Finding a route and technique to do achieve this safely and with a low risk of damage to urinary continence and erective function took well over 100 years, and involved contributions by many innovative surgeons, most of them in Europe.

A pivotal step in making radical prostatectomy a feasible and popular option for curative treatment of early prostate cancer was achieved by a serendipitous collaboration between a US surgeon and a retired Dutch urologist, that began in 1981. Together, they revealed as false the assumption that erectile dysfunction was an inevitable and permanent side effect of radical prostatectomy, and developed a technique that can avoid it.

This important advance hugely enhanced the practical value of the contributions made by the surgeons who went before them. In 1983, only 7% of men with prostate cancer underwent surgery. Ten years later, 70% of men with prostate cancer in their 50s and 55% of men in their 60s underwent surgery. Since that time, technical innovations have further improved the precision of both surgery and radiotherapy, while improvements in risk stratification and monitoring have opened the way for a third option, whereby patients with indolent prostate cancer can opt for regular monitoring, and keep active interventions on hold until the disease shows signs of progressing.

Identifying the prostate

Prostate surgery developed mostly by accident, and not only for cancer but for the much more common condition of a benign, enlarged prostate that often needs treatment. As Jonathan Goddard, a urologist who has been curator of the Museum of Urology of the British Association of Urological Surgeons, has described, surgeons encountered the prostate, sometimes with tumours, when they attempted to remove bladder stones, a procedure known as lithotomy, which also applies to other calculi such as kidney stones and gallstones.

Lithotomy is an ancient procedure for removing bladder stones, as memorably described by British urology surgeon Eric Riches, and could also involve breaking up the stones before removal, which is known as lithotrity. Riches said Ammonius of Alexandria, in about 200 BC, invented an instrument to break up large bladder stones. The procedure was done via the urethra, perineum or, eventually in the 18th century and after, by abdominal operations. These three routes were also to become ways of reaching the prostate.

Bladder stones are far more common in males, especially in older men, than in females, so lithotomy is mostly carried out on men.

Goddard noted that it was later, in the 3rd century BC, that Herophilus, a doctor in Alexandria, may have known about the prostate, and later again, in about 129–210 AD, that Galen of Pergamum wrote about “glands which poured a humor into urinary passages of the male to excite the sexual act”.

And much later again, it was European anatomists and surgeons, especially in Italy, France and Britain, in the 16th to 18th centuries, who began to describe the anatomy of the prostate, and crucially the enlargement that caused urinary difficulties, and also the connection with cancer.

Among the figures identifying the obstructive prostate were Jean Riolan the Younger in France and the famous Scottish anatomist and surgeon John Hunter. Goddard said indications that the prostate was associated with cancer were also made in the 18th century, but it was in the early 19th century that there were better descriptions of the disease.

He credited John Adams, an anatomist and surgeon at the London Hospital, as the first to differentiate between benign and malignant prostatic enlargement, in a book published in 1851, The Anatomy and Diseases of the Prostate Gland. Then, in 1853, Adams confirmed a case of prostate cancer with metastases, by histology.

Paths to prostatectomy

As surgeons began to refine urological surgery, with new instruments and for procedures such as lithotomy, via transurethral, perineal and abdominal routes, they encountered the prostate and sometimes cut off or pulled part of the gland off by hand.

In 1848, William Fergusson, professor of surgery at King’s College Hospital in London, showed at a meeting pieces of the prostate he had removed during lithotomy. According to Goddard, after performing about 200 lithotomies, Fergusson suggested that urinary symptoms were caused by the prostate and not by stones, and that enlarged lobes of the gland should be removed.

The prostate became a target for many surgeons in Europe and the US, with some colourful characters out to make names for themselves. But there is a critical difference between the boom in prostatectomies that ensued, which were mainly aimed at relieving the obstruction caused by the enlarged prostate, and operations for prostate cancer.

The former operation mostly does not remove all the prostate, only the constricting part, and can be done by a procedure known as simple or open prostatectomy, operating through the abdomen or perineum, or by inserting instruments through the urethra, in a procedure known as transurethral resection of the prostate (TURP). The aim is to ‘enucleate’ and remove the central portion surrounding the urethra within the prostatic capsule. Today it is usually done only if lifestyle changes and medical therapy fail, and there are several other direct treatments such as laser therapy and water ablation.

Radical prostatectomy, mainly carried out for cancer, is a much more comprehensive operation and removes the entire prostate, some surrounding tissue and also the seminal vesicles. Presently, it is mainly carried out through retropubic incisions directly to the prostate through the abdomen, but a perineal approach is also still in use.

Pick of the pioneers

Although it was to be many years before radical prostatectomy could be performed routinely with safety and without severe functional drawbacks, the surgical pioneers laid the foundations as they sought to address the benign enlargement that was causing so many difficulties for men, and also cancer.

A first partial prostatectomy for cancer is said to be the work of German surgeon, Theodor Billroth, in 1867 in Vienna, with other contemporary procedures by Swiss physician Emil Theodor Kocher, who later won a Nobel Prize for work on the thyroid. Billroth, regarded as the founder of modern abdominal surgery, accessed the prostate via the perineum. Before general anaesthesia, this was the obvious means of approach since the prostate was close under the perineal skin.

As Martin Hatzinger and colleagues reported, in The history of prostate cancer from the beginning to DaVinci [in German], in 1882 Heinrich Leisrink, a German surgeon, performed the first radical prostatectomy, removing the entire prostate via the perineum but without removing the vesicles. But other aspects of this surgery led to death of the patient in a few days.

Otto Zuckerkandl, a student under Billroth, brought more order to the surgery and modified the access route.

Meanwhile an array of surgeons, mainly in Britain and the US, were busy carrying out prostate enucleations via the suprapubic route (accessing the prostate through the bladder). These included Arthur Fergusson McGill in Leeds, and William Belfield in Chicago – the latter probably just beating McGill to the first open prostatectomy, in 1886.

One of the most colourful was an Irish surgeon, Peter Freyer, who claimed credit for a new approach to open suprapubic operations on the enlarged prostate, but faced a backlash from others on his claim of novelty, as Goddard reported (US surgeons Ramon Guiteras and Eugene Fuller seem to have told Freyer about the technique). Freyer first performed a suprapubic prostatectomy in 1900.

Working at St Peter’s, which was established in London in 1860 as the first urology hospital in Britain, by 1912 Freyer had published his 1000th case and was one of the high-volume surgeons of his time. Freyer’s legacy (for benign conditions) is described by Goddard and Michael Dinneen in Sir Peter Freyer: the man who gave the world prostatectomy.

An article by a New York based surgeon in 1898 provided a good summary of the approaches and pioneers then in play.

Claims for success with the radical cancer procedure also came early in the 20th century. It is commonly noted that it was in 1904 when Hugh Hampton Young, at Johns Hopkins Hospital in Baltimore, US, carried out the first successful radical prostatectomy via the perineum, with assistance from famous surgeon William Stewart Halsted (known especially for radical mastectomy).

However, there is evidence to indicate that a French surgeon with a famous name may in fact have successfully carried out the procedure before Young; namely Robert Proust, younger brother of the celebrated writer, Marcel Proust. As Reiner Speck writes in his article, Robert Proust – an eminent doctor in the shadow of his famous brother Marcel: “The young Robert Proust seems to have been completely captivated by these urological pioneers. His fields of activity and the resulting publications indicate this. Thus, (parallel to Young) he established the perineal access for prostatectomy (in French medical circles, it would in future be called ‘Proustatectomy’).”

As Hein Van Poppel and colleagues wrote in the book, Radical Prostatectomy – from Open to Robotic, Robert Proust described the technique of perineal prostatectomy for the first time in 1901, but Young gets the credit in most historical reviews for the first procedure, and others have said Proust did not operate until later.

Proust’s description, published in 1901, can be read at: Technique de la prostatectomie périnéale; Young – who spent many more years on this work – published a retrospective on his approach and, among many other appraisals, there is a podcast on Young.

Changing the approach

According to Rob Pelger, chair of the department of urology at Leiden University Medical Centre, Netherlands, surgeons were wary of attempting the radical operation through the abdomen (as is standard now) rather than the perineum because it was considered too risky.

“Nowadays, abdominal surgery would seem the obvious way to get to the prostate, but the risk of osteitis of the pubic bone and pelvic sepsis used to be considered too great,” said Pelger, who has researched the history of radical prostatectomy. “Also, because of the risk of bleeding, surgeons would have to tie off the venous flow from the penis so you would get thrombosis of the penis. They were also worried about pelvic cellulitis around the bladder, which is something I’ve never seen.”

Hugh Hampton Young did achieve some cancer cures, although many prostate cancers were well-advanced at diagnosis at the time.

In 1908, Willem Jacob van Stockum, in Rotterdam, Netherlands, is said to have performed the first retropubic (via the lower abdomen) prostatectomy, but he did not pursue this and the idea did not become popular. The retropubic approach provides direct access to the prostate, whereas suprapubic usually involves opening the bladder to reach the prostate, but there are different advantages (see this article in the context of benign enlargement; suprapubic is today not indicated for cancer treatment).

Surgeons continued to try various approaches for radical prostatectomy, including persevering with the perineal route. According to Martin Hatzinger and colleagues, a French surgeon, Joaquim Albarran in Paris, also pursued the perineal operation soon after Proust, and then René Leriche, a surgeon famous for pioneering vascular operations, is said to have performed the first suprapubic radical prostatectomy.

Other contributors, added Hatzinger and colleagues, include Friedrich Voelcker in Germany, who “created the so-called ischiorectal prostatectomy in 1924”; in 1952 there was “the sacroperineal approach according to Edmund Thiermann,” and in the same year there was “the sacral prostate removal according to Richard Bösehörer”.

US surgeons Roderick Turner and Elmer Belt modified Young’s perineal approach and published a series of 229 cases, starting in 1930.

But it was Irish urological surgeon Terence Millin who was to prove most influential at this time. In London, working at All Saints Hospital, a urological hospital, he decided to explore a different retropubic abdominal approach for removing tissue from benignly enlarged prostates, and published his findings in The Lancet in 1945, Retropubic prostatectomy: a new extravisceral technique (with reference to van Stockum’s work). This paved the way for the modern approach to prostate cancer surgery.

“He didn’t see any problems,” said Pelger. “He saw that the drainage was different than previously thought. He started using wound drains, which were not common at the time, so if there was leakage it would go through the drain and not stay in the tissues. Previously, it had been forbidden territory to operate in this way.”

The serendipitous ways by which Millin developed his retropubic approach and reduced objections to the “three great bugbears” of open prostatic surgery – bleeding, infection and urinary leakage – are well-described in The birth of retropubic prostatectomy – Millin.

For treating benign enlargement, Millin’s technique became a mainstay and he became a world famous and much sought-after surgeon and published a bestselling book in medical circles, Retropubic Urinary Surgery.

There followed efforts by other surgeons to refine the approach, such as by Henry Souttar in Britain and, in the US, surgeons such as Joseph Memmelaar, Richard Chute and Edward Campbell. The refinements are described in the article Radical retropubic prostatectomy: origins and evolution of the technique.

Yet radical prostatectomy remained a procedure that was both risky – not least due difficulties controlling bleeding – and also unpopular, due to the impact on quality of life. Long-term urinary incontinence was a frequent consequence of the operation, and long-term loss of erectile function was so common as to lead to the assumption that the nerves that control erection must run through the prostate, and could not be saved.

With the development of radiotherapy technology and capacity in the 1960s, this became the modality of choice for curative treatment of prostate cancer. Though survival rates were not as high as with surgery, it was a much better option in terms of preserving long-term quality of life. As a consequence, the efforts of the early pioneers of radical prostatectomy were only rarely put to practical use.

Reviving radical surgery

This was the situation in in 1974, when the US urologist Patrick Walsh was appointed director of the James Buchanan Brady Urological Institute at Johns Hopkins Hospital. The Institute had been set up by Hugh Hampton Young, the surgeon who in 1904 had pioneered the first radical prostatectomy to be done in the US. Yet 70 years later, Walsh found that total surgical removal of the prostate was rarely performed, even there. Walsh took it upon himself to try to build on the work done by Young and all the other pioneers, by exploring possibilities for resolving some of the associated complications.

He started by addressing the problem of blood loss. During surgeries for other urological procedures, he would take the opportunity to observe and record the structures of the vasculature around the prostate. He then used that knowledge to develop a technique for radical resection of the prostate that significantly reduced bleeding and also preserved urinary control by avoiding damage to the sphincter of the urethra – easier to do once this tightly packed complex area was less obscured by heavy flows of blood.

His approach was published in 1979.

With Walsh’s new technique, radical prostatectomy became less risky and less damaging to quality of life, making it a much more attractive option for curative treatment of prostate cancer than it had previously been. Walsh soon saw patient numbers increasing, and it didn’t take long before one of them reported to him, at a three-month follow up, that he had regained full potency.

That was the first indication Walsh – or anyone – was aware of that it might be possible to remove the entire prostate while preserving the nerves that control the erection. Walsh wanted to find out how this could be achieved. However, the pathways of nerves were not as easy to track during the course of urological operations as the pathways of vasculature structures had been. And as Walsh was to write much later in 2023, “The answer was not available in any textbook.”

And that is where Walsh’s highly significant progress in improving the technique of radical prostatectomy may have ended, were it not for the fact that, on the other side of the Atlantic, Pieter Donker, who had served as the first full professor and head of urology at Leiden University Medical Centre, in the Netherlands between 1968 and 1979, had recently taken retirement.

Pieter Donker: the draw of anatomy

The unlikely story of Donker’s historic collaboration with Walsh to develop a nerve-sparing procedure for radical prostatectomy is told more fully in “The Dutch urologist who paved the way to protect erections and continence in radical prostatectomy”.

Key to the story is that, in his retirement, Donker had immersed himself in producing highly intricate depictions of the pelvic anatomy, working in an anatomic laboratory at Leiden. For this purpose, he chose to work on the cadaver of a stillborn male – a choice that Donker understood would increase the chances of finding the nerves compared with dissecting an adult cadaver, as the nerves are relatively thicker in an infant cadaver than an adult, and connective tissue and fat can be removed more easily.

The potential for this project to throw a light on how Walsh’s patient had reported recovering full potency after a radical prostatectomy could not have been more obvious. However, Walsh was unaware of the progress Donker was making in mapping the anatomy of the pelvic area, and Donker was unaware of Walsh’s clinical discovery that that cavernous nerve did not run through the prostate, as previously assumed.

It wasn’t until 1981, when Walsh visited Leiden at the invitation of Donker’s successor Udo Jonas, that the two men were able to have the conversation that revealed the potential importance of what they could do together. Even then, the conversation which took place on the final day of the visit, was entirely unplanned, and only happened after Walsh turned down Donker’s invitation to show him around a local windmill museum, suggesting instead that Donker show him what he’d been working on since his retirement.

Once in the anatomy lab, Walsh quickly understood the potential to get the answer to the questions he had been asking, so Donker set to work there and then. It took three concentrated hours, with Donker carefully working away under the dissecting microscope, for them to discover the location of the nerves that control erectile function – tiny filaments, situated outside the capsule and fascia of the prostate.

The two agreed to continue working on the problem on separate sides of the Atlantic.

Transatlantic collaboration

The implications for the feasibility of radical prostatectomy as a curative treatment for prostate cancer were huge. Donker and Walsh began to correspond, exchanging theories, anatomical observations and detailed drawings, and collaborating on a landmark paper published in 1982, which concluded that: “…impotence after radical prostatectomy results from injury to the pelvic nerve plexus that provides autonomic innervation to the corpora cavernosa. Further studies will be necessary to determine whether refinements in surgical technique… can prevent this complication.” The paper included Donker’s detailed pencil drawings of the region, based on the infant dissection.

Walsh returned to Leiden in March 1982, by which time Donker had confirmed their original observations with further anatomical studies on a well-preserved male cadaver. Back in the US, Walsh then used his new knowledge to perform a radical cystectomy (removal of bladder and prostate). Ten days after his operation the patient awoke with an erection.

On 26 April 1982, Walsh performed the first purposeful nerve-sparing radical retropubic prostatectomy. This man lived a normal life and died free of cancer 35 years after surgery.

In 1983, Walsh published details of his nerve-sparing technique, which showed how to preserve the nerves by making precisely placed incisions along the lateral pelvic fascia tissue.. The paper included results of a series of 12 men who underwent the procedure, all of whom had experienced erections 10 months after, with six achieving successful vaginal penetration and orgasm.

Rapid uptake of surgery

With the risk of losing erectile function now considerably reduced, the option of radical prostatectomy to treat localised prostate became much more attractive. In 1980 only 7% of men with localised prostate cancer underwent surgery in the US. By the mid-1990s, the figure had risen to 70% of men in their 50s, and 55% in their 60s. In England, the number of radical prostatectomies increased nearly 20-fold between 1991 and 1999. With the means to cure becoming available alongside improvements in early detection through PSA screening, prostate cancer mortality fell significantly both in the US and Europe during the same decade.

Pieter Donker’s legacy to urology lasts in his detailed correspondence, a large collection of tissue slides, his remarkable anatomical drawings, and the generous assessment of Patrick Walsh – who at the International Congress on the History of Urology in March 2023, asserted that nerve sparing radical prostatectomy was definitely a European discovery.

What came next?

In the 1990s, surgeons in Europe and the US turned to less invasive, laparoscopic techniques to replace open retropubic surgery but it is a challenging operation. In 1998, surgeons at Montsouris Institute, Paris, started on a laparoscopic technique that was feasible and reproducible.

Shortly after, robot-assisted prostatectomy, using the da Vinci system, was described in 2001 by Jochen Binder and Wolfgang Kramer at Goethe University, Frankfurt, Germany, ushering in a technique with advantages such as better visualisation and easier tool handling – but at great financial expense.

Both retropubic and perineal radical prostatectomies are also performed today according to priorities such as nerve sparing and recovery.

References

Series by Jonathan Goddard:

The history of the prostate, part one: say what you see

History of the prostate, part two: the cause of urinary symptoms

History of the prostate, part three: ‘the size of a filbert!’, open surgery

The birth of retropubic prostatectomy – Millin, by Ashton Miller and Michael Staunton, in the Journal of the Royal Society of Medicine

Terence Millin (1903–1980) by Jonathan Charles Goddard and Michael Dinneen in Trends in Urology & Men’s Health

Two hands in one glove (article by Rob Pelger on Pieter Donker)

Anatomic radical prostatectomy: evolution of the surgical technique, by Patrick Walsh, in the Journal of Urology

Nerve-sparing radical prostatectomy: a European discovery? By Patrick Walsh, in European Urology Today

The discovery of the cavernous nerves and development of nerve sparing radical retropubic prostatectomy, by Patrick Walsh, in the Journal of Urology

Masterclass: Anatomic nerve sparing prostatectomy. Presenter: Patrick Walsh. Contains account of work with Pieter Donker

First filmed prostate surgery:

The First Filmed Prostatectomy, 1917: 100 Years of Movies in Urological Education

YouTube video

British Association of Urological Surgeons: Virtual Museum of Urology