Prostate

focal therapy for single focus, intermediate-risk prostate cancer

A/Prof Grummet has been a pioneer of focal therapy in Australia, performing the first case of focal brachytherapy with radiation oncologist Dr Andrew See in 2015. He is a co-principal investigator of the active LIBERATE focal brachytherapy clinical registry, which published its first paper in 2021. He is active within the international Focal Therapy Society, having attended their 2019 International Symposium in Kyoto, educating through webinars and contributing to the Society’s official textbook.

See the PCFA-hosted webinar on the LIBERATE focal brachytherapy registry here.

A/Prof Grummet is also trained in the use of focal irreversible electroporation (IRE/Nanoknife), offering this as an alternative, in addition to focal brachytherapy.

Why focal therapy?

Academic institutions around the world are now busy studying various forms of focal therapy for prostate cancer. Focal therapy aims to target only the cancer, leaving the remaining healthy prostate intact. The idea is to minimise side effects commonly seen with the standard whole gland treatments of radiotherapy and prostatectomy (such as erectile dysfunction, urinary incontinence and bladder and bowel urgency) and the early results are extremely promising.

This flurry of research activity is driven by our now superb imaging of prostate cancer using both MRI and PSMA PET, which finally allow us to see where the cancer is within the prostate. Such imaging has led to major advances in diagnostic accuracy, allowing biopsies to be targeted to the cancer. But the obvious offshoot is also to the step change in therapeutic accuracy which is focal therapy.

Different sources of energy (modalities) are being explored in focal therapy including focal brachytherapy (radiotherapy by seed implantation), irreversible electroporation (IRE/Nanoknife), HIFU and cryotherapy. However, which modality is superior remains unknown at present. It may be that different modalities have their own advantages in different situations, such as the location of cancer within the prostate.

Advanced Diagnostics for Prostate Cancer

MRI-targeted prostate biopsy - See article on A/Prof Grummet in Fairfax Media June 2016

When the presence of prostate cancer is suspected by an elevated PSA or an abnormal-feeling prostate on digital rectal examination (DRE), an ultrasound-guided biopsy of the prostate has traditionally been performed. However, the ultrasound is only guiding the biopsy needles to the prostate itself, rather than to any cancer that may be within the prostate. It is therefore an essentially blind procedure, randomly sampling the prostate gland. As a result, cancer can sometimes be missed.

Evidence is now rapidly accumulating both here in Australia and abroad of the value of using MRI (Magnetic Resonance Imaging) for prostate cancer diagnosis. Using multiple parameters (multiparametric) and a standardised reporting system, MRI now enables targeting of biopsies to areas within the prostate that are suspicious of being cancer, leading to far greater accuracy in diagnosis. The potential ramifications of this improvement in diagnosis are huge, not only for individual patients, but also for the efficiency of healthcare delivery to all men at risk of having prostate cancer.

Hear Dr Norman Swan's Radio National interview with Australian researcher Dr Les Thompson on MRI in prostate cancer diagnosis.

Associate Professor Grummet has extensive experience in MRI-targeted prostate biopsy and is a keen advocate for its broader use and development. In 2014 he established the regular MRI Prostate Multidisciplinary Meeting at Epworth Healthcare, where urologists, radiologists and pathologists meet to discuss cases and accelerate each others' expertise in this field. He has also presented on MRI-targeted biopsy as an invited speaker at various conferences and published in the Medical Observer magazine.

See more in A/Prof Grummet's blog on MRI-Targeted Prostate Biopsy.
 

Transperineal prostate biopsy

Due to the prostate's close proximity to the rectum, the traditional method of taking prostate biopsies has been by passing biopsy needles through the rectal wall (TRUS - transrectal ultrasound). However, in recent years accumulating evidence shows an increasing rate of serious infection (sepsis) with this technique, most likely due to the rise of multi-drug-resistant bacteria living in the rectum.

Transperineal biopsy is performed under a general anaesthetic via the perineal skin (behind the scrotum). Unlike the rectum, the perineal skin is easy to disinfect. As a result, A/Prof Grummet's research group and others have found a zero or near-zero rate of sepsis using this technique. A/Prof Grummet's findings were published in the British Journal of Urology in 2014.

Not only can individual patients benefit from the reduced risk, but transperineal biopsy can also reduce the unnecessary use of strong broad-spectrum antibiotics. This has the potential to benefit the community as a whole by helping to avoid the further development of multi-drug-resistant bacteria.

Using a fixed grid for needle placement, transperineal biopsy also lends itself well to targeted biopsies of suspicious areas on MRI.

See more in A/Prof Grummet's blog on Transperineal Biopsy

Active surveillance of low risk prostate cancer

Prostate cancer represents a whole spectrum of disease, ranging from indolent (generally harmless) to lethal. Due to PSA testing, most prostate cancer diagnosed nowadays is at the lower risk end of this spectrum. Exact definitions vary slightly, but low risk prostate cancer typically means a PSA less than 10, a tumour that cannot be felt on digital rectal examination (DRE) of the prostate, and a low volume of cancer with a Gleason score of 3+3=6 (ISUP Grade Group 1) on biopsy.

It is now well-recognised that the vast majority of men diagnosed with low risk prostate cancer can be safely monitored instead of requiring immediate curative treatment, which comes with its risk of side effects. This monitoring in men with a general life expectancy of over 15 years is called active surveillance and involves repeat PSA testing and DRE over time. Currently, a repeat "confirmatory" biopsy is required within 12 months of initial diagnosis to reduce the risk of missing the presence of higher risk cancer. However this recommendation is based on the initial biopsy being a TRUS biopsy without a prior MRI. With the advent of MRI-targeted biopsy, enabling more accurate diagnosis from the outset, how we perform active surveillance is in evolution.

If during active surveillance of a man with low risk prostate cancer, there is evidence of the disease becoming more aggressive, such as a PSA rising too fast, or a repeat biopsy showing a higher Gleason score, then curative treatment can be appropriately given. However, many men on active surveillance should be able to avoid curative treatment altogether, as long as their disease remains stable.

A/Professor Grummet is a keen advocate of active surveillance as it reduces the unnecessary overtreatment of harmless disease, thereby maintaining men's quality of life. Active surveillance is also important as its widespread use for low risk prostate cancer strengthens the argument in favour of PSA testing, which can help find the more aggressive types of prostate cancer while they are still curable.

A/Professor Grummet has a large volume of men on active surveillance in his practice and is a site investigator on the PRIAS study, the largest observational study of men on active surveillance in the world.
 

Treatment of high risk localised prostate cancer

Men who may stand to gain the most from an early diagnosis of prostate cancer are those with high risk clinically localised cancer. This is defined as having a PSA of over 20, or a tumour that can be felt on DRE to extend beyond the edge of the prostate gland (clinical stage T3), or a Gleason score on biopsy of Gleason 4+4=8 (ISUP Grade Group 4 ) or higher, or any combination of the above. And there is no sign of cancer elsewhere in the body on routine imaging such as a bone scan of the whole body or a CT of the abdomen and pelvis. These patients are defined as high risk because even with localised treatment of the prostate with the intention to cure (surgery or radiotherapy), many patients will eventually be found to have disease that has spread beyond the prostate, but was too small to detect at the time of diagnosis, and has not been cured.*

*Note: PSMA (prostate specific membrane antigen) PET scanning is changing all this. Whilst not yet in clinical guidelines (as at January 2018), PSMA PET has been in wide clinical use in Australia since 2016. Evidence shows that PSMA PET is far more sensitive at detecting metastatic prostate cancer than the old standard tests of CT and bone scan. As a result, many patients with high risk cancer are now found to have spread to nearby lymph nodes in the pelvis on PSMA PET. It is currently unknown what the best management of this situation is. However, based on evidence in the pre-PSMA PET era, aggressive local treatment, such as with radical prostatectomy and extended pelvic lymph node dissection, may improve survival.

For a comprehensive review of the capability of PSMA PET and the evidence supporting it, along with real case examples, download the invited presentation delivered by A/Prof Grummet at the 2016 Urological Association of Asia meeting in Singapore.

The important point however, is that overall most patients with high risk localised prostate cancer are in fact curable with local treatment and should not be denied it. Surgical removal of the prostate (radical prostatectomy) and radiotherapy are the two treatment options. A/Professor Grummet has published research on the Vancouver experience of surgery for high risk localised prostate cancer and is a strong advocate for its use in the appropriate circumstances.

Potential advantages of surgery include:
> Full pathological staging of the disease, including tissue assessment of both the whole prostate gland as well as pelvic lymph nodes, for the most accurate prognostic information
> Extensive removal of pelvic lymph nodes has the potential of being therapeutic as well as prognostic, i.e if the volume of cancer that has spread to these removed lymph nodes is small, cure is still possible, albeit in the minority of cases
> Surgery alone is often curative
> The effectiveness of treatment is easily monitored by the PSA level, which can become undetectable in just 6 weeks post-operatively
> If surgery has not removed all the cancer, and the only remaining disease is still localised within the pelvis, radiotherapy can still be used to achieve a potential cure; in other words, surgery is the most appropriate primary treatment if multimodal therapy is required
> If surgery, even as part of multimodal therapy fails to cure the cancer, it is still likely to achieve excellent local control, avoiding the potential complications of urinary obstruction, bleeding and pelvic pain that can occur with locally advancing disease

The potential disadvantages of surgery include: it is a major operation with the attendant risks of major surgery; potential long-term side effects of erectile dysfunction and less often, urinary incontinence. The alternative to surgery for initial treatment of high risk localised prostate cancer is a combination of radiotherapy and hormone therapy.

Robotic prostatectomy

Radical prostatectomy can be performed by either a traditional open or minimally invasive (keyhole) approach.

Robotic prostatectomy is a form of keyhole surgery where the robotic device is interposed between surgeon and patient. Importantly, the surgeon precisely controls every movement the robotic instruments make. The robot does not perform any actions autonomously and is therefore more accurately termed a master-slave device. The robotic instruments enable more degrees of freedom of movement than the human hand and are therefore ideal for performing complex reconstructive surgery in a confined space, such as joining the bladder to the urethra deep in the pelvis during a radical prostatectomy.

Like any keyhole surgery, robotic prostatectomy causes less trauma to the abdominal wall than open surgery, leading to a faster recovery time. A/Professor Grummet performs both robotic and open prostatectomy depending on each individual patient's circumstances.

See more about robotic prostatectomy on the video gallery page

For more information on prostate cancer generally, visit the European Association of Urology's EAU Patient Information website.

Benign enlargement of the prostate

As men age, the prostate gland commonly enlarges to a varying degree (benign prostatic hyperplasia, BPH). This process is entirely distinct from prostate cancer. Because the prostate surrounds the urethra at the bladder outlet, this benign enlargement can constrict the outlet and commonly causes bothersome symptoms which can affect a man's quality of life. These lower urinary tract symptoms (LUTS) include getting up multiple times at night to urinate, having a weak flow that may be difficult to start, and needing to rush to the toilet due to a strong urge to urinate.

See more in Foundation 49's More Than Once a Night campaign

Fortunately, there are very effective treatments available. Sometimes only simple lifestyle changes are required. There is also an array of medications which have been rigorously tested in randomised control trials and found to be effective.

If symptoms are severe, or if there are complications of bladder outlet obstruction, such as the inability to urinate at all (acute retention), or inadequate bladder emptying (chronic retention), surgical treatment may be required. Whether laser energy or electrocautery is used, the basic principle of surgery is to remove the obstructing prostatic tissue, and is the most effective treatment of symptomatic BPH. This is routinely done using a minimally invasive approach via an instrument passed down the urethra (cystoscopy).

A/Prof Grummet regularly treats patients with bothersome LUTS using lifestyle advice, medication or surgery, depending on the individual patient's needs.

Learn more in A/Prof Grummet's article "Managing Voiding Issues" in the Medical Observer as listed on the Education page.

For more information on benign prostatic enlargement, visit the European Association of Urology's EAU Patient Information website.

Kidney

Kidney cancer

In the past, before imaging such as ultrasound and CT scanning were available, most cancers of the kidney were diagnosed when the tumour was large enough to cause symptoms such as blood in the urine (haematuria). Whilst this still occurs, the commonest way kidney cancers are diagnosed nowadays is incidentally, when a scan of the abdomen is done for other reasons. As a result, many of these tumours are quite small (less than 3 cm).  In elderly patients many of these small tumours, even if confirmed on biopsy as kidney cancer (renal cell carcinoma), can be safely monitored without intervention. Sometimes these small tumours are not even cancer, but rather a benign tumour of the kidney, such as an oncocytoma. It is therefore important to obtain a well-performed biopsy of these small kidney tumours to avoid unnecessary treatment. Larger kidney tumours do not usually require a biopsy, as they are far more likely to be cancer if they show the typical appearance of cancer on a CT scan.

When curative intervention is required, surgical removal is the treatment of choice. If deemed suitable, it may be possible to remove the tumour only, and preserve the rest of that kidney - an operation called a partial nephrectomy. However, if the tumour is too large or deemed unsuitable for a partial nephrectomy, the whole kidney is removed (radical nephrectomy). Radical nephrectomy is usually performed with keyhole surgery (laparoscopically) to reduce recovery time, unless the tumour has invaded into adjacent structures such as a large vein called the vena cava. As long as the remaining kidney has good function, the patient should be able to live a normal life on a single kidney.

A/Prof Grummet routinely performs laparoscopic radical nephrectomy and open partial nephrectomy for kidney cancer in the appropriate patients.

For more information on kidney cancer, visit the European Association of Urology's EAU Patient Information website.

Kidney stones

Stones (calculi) in the upper urinary tract can be a source of severe pain. Stones form in the kidney and may remain there, usually causing a pain or ache on that side if they are large enough. However, if a stone enters the ureter (the tubes running from each kidney to the bladder), it can be excruciating and require an emergency admission to hospital for pain relief.

Sometimes a stone in the ureter will pass on its own and the pain will stop. However, if it cannot pass, it needs to be removed. This is done under a general anaesthetic, often as a day case, using an instrument that is passed up through the urethra and bladder into the ureter (ureteroscopy). A laser fibre is then passed through the ureteroscope to destroy the stone. This minimally invasive technology, which is standard of care, enables complete stone treatment with minimal trauma to the body. If the ureter is too tight to admit the scope, a thin plastic tube (stent) is temporarily placed along the ureter internally, allowing dilation (expansion) of the ureter. Ureteroscopy with laser can then be safely and successfully performed as a second procedure within a few weeks.

Although not always possible, it is of course preferable to diagnose kidney stones while they are still in the kidney and before they cause severe pain. If they are too large to be capable of passing easily down the ureter, they should generally be treated. Whilst some stones can be dissolved chemically, the vast majority need to be removed or fragmented mechanically. Most stones in the kidney can be treated similarly to stones in the ureter, with ureteroscopy and laser, however a flexible ureteroscope is required and patients usually require pre-stenting, as described above. Other treatment options are external shock wave lithotripsy (stone-breaking), or for large kidney stones, keyhole surgery through the back (percutaneous nephrolithotomy or PCNL).

A/Prof Grummet performs all types of stone treatment, most commonly ureteroscopy and laser.

For more information on kidney stones, visit the European Association of Urology's EAU Patient Information website.

Genitalia

A/Prof Grummet regularly performs surgery for all the conditions listed below.
 

Testicular cancer

Cancer of the testicle (testis) most commonly affects young men and is typically found as a painless lump. However it sometimes arises in older men, and can occasionally be painful. Men should therefore regularly perform self-examination of their testes, just as women self-examine their breasts for breast cancer. If a lump is found, a man must see his GP who may then refer to a urologist for urgent assessment.

Various tests must be done first, but the diagnosis of testicular cancer is confirmed on microscopic examination of the tissue, which is almost always achieved by complete removal of the testis via an incision in the groin (inguinal orchidectomy). If desired, a life-like testicular prosthesis can be inserted at the time. Once cancer is confirmed, further imaging with CT scanning is performed to help rule out any evidence of spread.

Unlike most solid organ cancers, even if testicular cancer has spread, it is still usually highly curable with additional treatment. This is usually in the form of chemotherapy, but occasionally radiotherapy is used. In rare circumstances, major surgery may then be required to remove remaining tumours that have spread to lymph nodes in the abdomen.

Vasectomy

Vasectomy is a highly reliable form of male sterilisation. It is a simple procedure which can be performed under general or local anaesthetic, depending on the man's preference, and is a day case taking less than 20 minutes. Two very small incisions are made in the skin of the scrotum, then the vas deferens tubes, which carry sperm from the testicle, are cut.

Importantly, a man is not sterile straight after the procedure as there are still live sperm in the tubes "downstream" from where the tubes are cut. Other methods of contraception must therefore still be used to avoid a pregnancy until a sperm test, performed later, shows a zero sperm count.

Men undergoing vasectomy should consider the procedure as irreversible. Although microsurgical vasectomy reversal can be performed, there is no guarantee of its success.

Vasectomy does not interfere with sex drive (libido), erectile function, or orgasm. Even ejaculation is not noticeably different afterwards, as sperm from the testis only makes up a small fraction of semen. The remainder of ejaculated seminal fluid is mainly from the prostate gland.

Penile and scrotal conditions

Phimosis (tight foreskin)

A tight foreskin in men is usually caused by underlying inflammation, which can also affect the head (glans) of the penis (balanitis). It can be very painful during an erection and cause splitting and bleeding of the skin. Sometimes the tight foreskin can retract back over the shaft of the penis during an erection, but is then too tight to be pulled down again - a condition called paraphimosis. This is extremely painful and usually requires emergency treatment in hospital. To prevent this occurring, it is therefore important that phimosis is treated soon after it is first noticed. The most definitive treatment is circumcision.
 

Hydrocele (fluid in the scrotum)

Hydroceles are relatively common and usually do not require any intervention. However, they sometimes grow large and painful, and are felt as a swelling on one side of the scrotum. Rarely they may also signify underlying disease of the testicle. They are most definitively treated by surgical removal of part of the sac that contains the fluid inside the scrotum. Hydrocele fluid can also be sucked out with a needle (aspirated), but the fluid tends to re-accumulate.
 

Epididymal cysts

The epididymis is the first part of the tube that carries sperm from the testicle. It winds back and forth alongside the testis before straightening out into the vas deferens (see Vasectomy above).
The epididymis commonly forms cysts which, like hydroceles, usually require no intervention. They are felt as a swelling on one side of the scrotum but are usually more distinct than hydroceles. If an epididymal cyst is large and tight, it may be painful or bothersome enough to warrant treatment, which is surgical removal of the cyst.