John, a 61-year-old-man, visits his GP for an annual medical/physical assessment. His GP has been monitoring John’s prostate-specific antigen (PSA) levels on an annual basis, with stable readings ranging between 2.1-to-2.3. John has no significant lower urinary tract symptoms. His past medical history includes stable hypertension and high
cholesterol managed through medication. He has no family history of prostate cancer and is otherwise fit and healthy. His most recent PSA is elevated, at 5.2. This is repeated six weeks later by his GP and remains
high, at 5.3. His digital rectal examination is normal.
Prostate cancer is one of the leading causes of cancer in Irish men. Over 3,300 men are diagnosed with prostate cancer in Ireland every year, and it accounts for 11 per cent of all cancer-related deaths in Irish men. The major risk factors for prostate cancer are advanced age, race and ethnicity (highest incidence in black men) and positive family history.
The case study in this article is an example of a patient’s journey from elevated PSA to diagnosis and treatment, highlighting some recent changes in the diagnostic pathway, as well as the advent of increasing access to robotic surgery in treating Irish patients diagnosed with prostate cancer.
New National Cancer Control Programme (NCCP) guidelines
The NCCP has recently revised the referral criteria for men undergoing prostate/PSA assessments, which include important changes from previous referral guidelines.
Firstly, the age-specific PSA reference ranges have changed, with a reduction in the age-specific PSA reference ranges for referral for urological assessment. Secondly, the latest NCCP referral guidelines have lowered the age threshold for referral of asymptomatic men from 50 to 40 years.
In John’s case, he is 61 years old with a PSA of 5.3 and the new NCCP guidelines recommend referral if his PSA is four or greater, so John’s GP refers him for further urological assessment. John is seen by his urologist and undergoes a full urological assessment. In the past, John would have been counselled concerning his elevated PSA and recommended to go directly for a standard 12-core transrectal ultrasound (TRUS)-guided biopsy under local anaesthetic.
Further imaging, such as MRI, would have only been used to stage prostate cancer after diagnosis and/or before considering definitive treatment, such as surgery or radiotherapy.
Pre-biopsy MRI prostate
Contemporary TRUS biopsy of the prostate can have significant false-negative rates, with up to 30 per cent of clinically significant cancers being missed due to undersampling. This can lead to the need for repeated biopsies in patients with an elevated PSA and previous negative biopsy. This in turn further increases the risk for complications from biopsy, as well as potentially delaying diagnosis.
The standard of care has now shifted in how men with elevated PSAs are being investigated. There is an increasing use of multiparametric MRI (mp-MRI) prior to TRUS biopsy. Multiparametric MRI of the prostate has the ability to measure the movement of water in tissue (Brownian motion). Areas of high cellular density within a tissue (ie, in prostate cancer versus benign prostate tissue) restricts the Brownian motion, which is translated as a loss of signal in certain MRI sequences (ie, diffusion weighted imaging).
These images can be graded (PIRADS grading system v2), where higher scores refer to regions in the prostate that are more likely to harbour clinically-significant cancers (Figure 1). The use of mp-MRI prior to biopsy not only improves the diagnostic accuracy, but may also help avoid unnecessary TRUS-biopsies in certain men.
The recently-published PROMIS trial (Diagnostic accuracy of mp-MRI and TRUS biopsy in prostate cancer) in The Lancet suggests that MRI improves the detection of clinically-significant prostate cancers and may reduce unnecessary biopsies in up to 25 per cent of men in this study.
Furthermore, the increased use of MRI targeted/fusion biopsies and transperineal template biopsy techniques have greatly improved the diagnostic accuracy in men undergoing investigation for elevated PSA or clinical suspicion of prostate cancer and highlight a new standard of care in diagnosis.
Another large study, the PRECISION Trial, published in the New England Journal of Medicine, showed that risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard TRUS-guided biopsy in men at clinical risk for prostate cancer. All the men in this study had never had a previous biopsy, further supporting a fundamental paradigm shift in prostate cancer diagnostics. The Beacon Hospital and Tallaght University Hospital, Dublin, now offer men with elevated PSAs pre-biopsy mp-MRIs, with the option of MRI guided/fusion targeted biopsy.
Our case study patient, John, undergoes an mp-MRI, which finds a suspicious 8mm region graded as a high-risk PIRADS 4 lesion in the left mid-peripheral zone of his prostate. There is no evidence of pelvic lymphadenopathy. He then undergoes an MRI targeted fusion biopsy of his prostate to improve the diagnostic accuracy of biopsy. An MRI fusion biopsy is done using computer software that superimposes detailed MRI scans with live, real-time ultrasound images of the prostate. Suspicious areas are identified and marked and the MRI can be used to guide biopsy needles precisely to the lesion of interest (Figure 2).
John’s prostate biopsies are reported as a Gleason 4+3=7 (Prognostic Grade Group 3) in three/three of the targeted biopsies, three/three involving 50 per cent of all three cores. The other systematic biopsies are negative. John’s case is reviewed at a multidisciplinary team meeting and he is deemed to have intermediate-risk localised prostate cancer. He is reviewed in clinic to discuss his diagnosis and treatment options, which primarily include surgery or radiotherapy options.
Approximately 90 per cent of men who receive a new diagnosis of prostate cancer have cancer confined to the prostate gland (clinically-localised disease), which is potentially curable with treatment. Treatment options are tailored to the patient’s age, PSA level, grade and stage of prostate cancer, as well as the patient’s comorbid status and the patient’s personal choice. These treatments are broadly summarised in Table 1.
After meeting with both his urologist and radiation oncologist to discuss the benefits, risks and side-effects of each treatment option, John decides to undergo robotic laparoscopic-assisted prostatectomy (RALP).
Robotic surgery for prostate cancer
The aim of radical prostatectomy is to remove the prostate gland and the cancer within it. Traditionally, open surgery is performed through a lower mid-line incision below the umbilicus. Alternatively, minimally-invasive surgery may be performed using much smaller multiple laparoscopic incisions. Robotic surgery is one of the latest technological advancements of minimally-invasive surgery.
In the last decade, surgical robots have literally transformed the way doctors operate and have become the standard surgical approach to many operations, including prostate cancer surgery. The technology is significantly more expensive in comparison to open surgery and therefore up to recently has only been available in the private sector. More recently, robotic technology is slowly being introduced to public hospitals or where public patients have access/funding to undergo robotic surgery in a private hospital.
During surgery, four robotic arms are inserted into the patient though small incisions in the abdomen. One arm is a camera, two act as the surgeon’s hands, and a fourth arm may also be used to assist the surgeon while operating. The patient is surrounded by a complete surgical team, while the surgeon is seated nearby at a separate console. The surgeon uses a three-dimensional image viewfinder, which provides a high-definition view of the surgical field. The surgeon operates with hand controls and foot pedals to direct multiple instruments during surgery (Figure 3).
The robotic arms have the ability to filter-out any tremor in the surgeon’s hands and increase the surgeon’s range of motion. This enhanced precision is especially helpful to a surgeon during delicate portions of the operation. With all of these advantages, robotic surgery provides significant benefits over traditional open procedures, including shorter hospital stay, less blood loss, less pain and faster return to normal activities.
Despite the advantages of robotic surgery, as highlighted above, benefits to oncological and functional outcomes is controversial and ultimately, is more limited to the surgeon’s training and experience than the technology used. One of the few randomised, controlled trials in this area was done in Australia and examined outcomes between robotic versus open surgery for prostate cancer. It essentially showed equivalence between the two groups, demonstrating that the surgeon is above any technology and method.
The NCCP has revised the referral criteria for men undergoing prostate/PSA assessments. Age-specific PSA reference ranges have been reduced for urology referral. Also, the age threshold for referral of asymptomatic men has been lowered, from 50 to 40 years.
Pre-biopsy mp-MRI of the prostate is becoming standard practice in the majority of men being investigated for elevated PSAs prior to undergoing prostate biopsy.
Robotic surgery for prostate cancer has significant advantages to open surgery. Access to robotic surgery in Ireland is increasing for both public and private patients.
References on request