In Australia prostate cancer is the most prevalent non skin cancer in men with 1 in 7 men diagnosed with prostate cancer by the age of 75 years. (1) PSA screening has led to a stage shift into a lower volume prostate cancer with a marked decline in the presentation of high volume or metastatic prostate cancer upon diagnosis. This has been associated with a decline in prostate cancer death (2). PSA has also led to an increased risk of diagnosis of a low volume, potentially clinically insignificant prostate malignancy.
Current options for management of localised prostate cancer in Australia will be discussed.
Active surveillance
PSA screening has led to an increased number of patients diagnosed with low volume, potentially insignificant risk prostate cancer and these patients have a low probability of prostate cancer specific death over a 10 – 15 year period. Therefore in this sub-group of patients active surveillance as initial management would seem appropriate.
Active surveillance is not watchful waiting. Active surveillance implies an initial conservative approach to prostate cancer management, with definitive curative treatment offered to patients who show signs of progression of prostate cancer during the active surveillance protocol. Active surveillance is usually considered appropriate for patients with low volume Gleason score 3 + 3 = 6 adenocarcinoma, non-palpable cancer on digital rectal examination (or a small nodule stage T2a malignancy ) and a PSA level of < 10.
Some active surveillance protocols also include low volume Gleason score 3 + 4 = 7 malignancy. The risk of prostate cancer specific mortality on published active surveillance protocols is <5% over a 10 year period. (3) Active surveillance is becoming more common in Australia for management of Gleason 3 + 3 = 6 malignancy. Over 40% of patients receive no active treatment when diagnosed with low risk prostate cancer in Victoria between 2008-2011(11), with increasing acceptance of active surveillance protocols in current times.
The triggers for intervention include progression to higher volume or higher grade disease on surveillance biopsy, PSA doubling time < 3 years, or change in patient preference towards definitive treatment. (4)
An area of great promise in active surveillance protocols is multi-parametric MRI prostate techniques, which have increased the accuracy in detecting prostate cancer compared to standard MRI & TRUS. A 3T mpMRI can detect clinically significant prostate cancer with 90% accuracy (5) and this technology may decrease the frequency of repeat biopsy procedures during the active surveillance period.
The limitations of active surveillance include patient anxiety and the potential loss of curability during the active surveillance period. The role in active surveillance in men under the age of 60 years at the time of diagnosis will become clearer when 20 year data is available.
Radical prostatectomy
Radical prostatectomy remains the gold standard of management of localised prostate cancer in Australia. Radical prostatectomy has been associated with excellent long term survival and clinical local control.
The main potential complications of a radical prostatectomy, from a quality of life point of view, are impotence and a small risk of bothersome long term urinary incontinence. Maintenance of erectile function post radical prostatectomy depends on whether a nerve sparing procedure has been performed, the patients pre-operative erectile capacity, the experience of the surgeon in performing nerve sparing techniques and also the definitions used for recovery of erectile function. Potency rates vary widely in the literature from 25 – 94%. In general, a male diagnosed with prostate cancer between the age of 60 – 70 years has a 50 – 60% chance of recovery of erectile function with a bilateral nerve sparing procedure.
The risk of urinary incontinence is also determined by surgeon experience, surgeon technique and the definition used for incontinence. When the defining urinary incontinence as no pad usage, the risk of incontinence ranges from 2 – 25%, with the majority of large institutions with high volume surgeons reporting < 5% risk of bothersome long term urinary incontinence requiring further treatment such as a sling or artificial sphincter procedure.
Robotic assisted laparoscopic surgery is becoming a more popular technique for a radical prostatectomy procedure. Robotic radical prostatectomy was first commenced in Australia at the Epworth Hospital by Drs Costello / Peters in 2003. Since that time over 14,000 robotic radical prostatectomies have been performed in Australia up to 2013, consistent with the world wide increase in robotic surgery. In 2012 robotic techniques were used in 38% of the radical prostatectomy procedures in Australia and 79% of private radical prostatectomy procedures in Queensland in 2013.
The potential advantages of a robotic assisted laparoscopic radical prostatectomy include less post operative pain, decreased hospitalisation periods, less intra-operative bleeding, an earlier return to activities of daily living and an earlier return to the work environment.
Functional differences between open and robotic assisted laparoscopic techniques have been recently addressed by meta-analysis studies . The meta-analysis of open vs. robotic surgery by Ficarra showed that although numerous factors influenced the recovery of potency, there is a significant advantage in erectile function recovery in favor of robotic prostatectomy at 12 months post-op. (6) A further meta-analysis by the same authors also showed that recovery of urinary continence is influenced by numerous factors including surgeon experience, patient characteristics and surgical technique. However this is the first paper to show a statistically significant advantage in favor of robot surgery in terms of recovery of urinary continence at 12 months post-op. (8) However randomised studies will be required to confirm the findings of these recent publications.
The Royal Brisbane Hospital is one of the few institutions in the world to commence a randomised open vs robotic radical prostatectomy trial. (9) This trial commenced in 2010. Four hundred patients will be randomised (200 in each arm) and by June 2013, already 270 patients have already been randomised, with 241 having completed surgery. It is anticipated that this important surgical trial will finish recruitment by the end of 2014.
Low dose rate prostatic brachytherapy
Brachytherapy techniques allow delivery of much higher radiation doses into the prostate than can be achieved by standard external beam radiation techniques. This gives the potential for improved long term local cancer control. At the same time there is less dose received by the rectum, which can potentially decrease the risk of long term rectal complications.
Brachytherapy techniques also allow delivery of higher doses of radiation directly into the known tumour areas of the prostate.
The lack of randomised trials between brachytherapy and surgery make it difficult to compare and contrast these modalities with respect any difference in long term cancer specific survival. Nevertheless the published data on brachytherapy shows a similar 15 year overall and cancer specific survival rates to a radical prostatectomy. (10) There does appear to be less risk of impotence and incontinence of urine with brachytherapy, although up to 30% of patients become impotent within 3 years post implant. There is a higher risk of bladder filling symptoms and burning in the urine (dysuria) following a brachytherapy implant compared with a radical prostatectomy. Brachytherapy obtained a Medicare rebate in Australia 2003 which increased its popularity, however numbers have decreased over the last couple of years consistent with the increased uptake of surgery with robotic radical prostatectomy technology.
External Beam radiotherapy (IMRT)
External beam radiotherapy in Australia has traditionally been the main treatment option for locally advanced prostate cancer, or in patients with localised prostate cancer that are considered as not suitable (medically unfit) to undergo a radical prostatectomy. The improvement in delivery of radiotherapy with image guided techniques has allowed for an increase in the dose delivered to the prostate, without significantly increasing the risk of damage to surrounding structures, such as the bladder and rectum. Based on overseas data, this radiation dose escalation (particularly with doses > 74Gy) has resulted in improved long term local control and decreased PSA failure compared with standard radiotherapy techniques used over 10 years ago. However IMRT can not deliver doses to the prostate as great as with a brachytherapy implant.
The complications of IMRT include chronic rectal symptoms, such as frequency / urgency of bowel motions, rectal mucus production and bleeding form the rectum.
High dose rate brachytherapy
Increasing the radiation dose delivered to the prostate (radiation dose intensification) has led to improved long term local control and biochemical freedom from recurrence of prostate cancer. One method of radiation dose intensification is with high dose rate prostatic brachytherapy, via the use of iridium 192 source, delivered via temporary transperineal HDR brachytherapy needles inserted into the prostate.
In Australia high dose rate brachytherapy is usually performed with 3 fractions of radiotherapy, usually between 6.5 – 7Gy per fraction, delivered to the prostate over a 30 hour period via the brachytherapy rods. . More recently some centres have changed to a single fraction of 15Gy. Thereafter external beam radiotherapy is delivered to the prostate on a daily basis over a 5week period (46Gy in total) . This increases the intra-prostatic prostate radiation dose compared with standard EBRT / IMRT techniques.
Each State in Australia has a centre with the ability to perform high dose rate brachytherapy.
Our unit at the Wesley Hospital in Brisbane has performed > 1000 HDR brachytherapy procedures since our first procedure in August 2000. Our results have shown an improvement of local control and better “cure” of prostate cancer compared to previous external beam radiation techniques.
HDR brachytherapy is performed for high risk prostate cancer, or patients with multiple intermediate risk factures, who are assessed as not appropriate for a radical prostatectomy procedure.
The potential complications of HDR brachytherapy include a 5 – 10% risk of a urethral stricture and a 50% risk of impotence.
Cryotherapy
There is only two cryotherapy units in Australia (Sydney and Cairns) and there has been no recent scientific publications from these units regarding long term outcome > 5 years post treatment.
High intensity focused ultrasound ablation
High intensity ultrasound focused ablation of the prostate is an uncommon treatment of localised prostate cancer. This treatment may increase in popularity if focal therapy becomes a treatment option for prostate cancer in the future.
New therapies
Cyberknife robotic radiosurgery system is an image guided radiotherapy system with computer controlled robotics to precisely deliver a high dose of radiation to the prostate over 5 days. Australia’s first Cyberknife system was installed in Perth in 2013.
Nanoknife technology uses irreversible electoporation, causing cell death by strong local electric fields which effects parenchyma and tumour cells but not vessels or nerves. This technology may be suitable for focal prostate cancer treatment. Sydney commenced a Nanoknife focal therapy trial in 2013.
Summary
Active surveillance is becoming an accepted initial treatment by Australian urologists for low volume, low grade Gleason score 3+3=6 prostate cancer.
Radical prostatectomy remains the most common management of localised prostate cancer in Australia. Robotic assisted laparoscopic radical prostatectomy is becoming a more common surgical option and is associated with the advantages of minimally invasive surgery, without a decrease in cancer control or functional outcome.
Image guided techniques have improved the outcome and side effect profile of external beam radiotherapy (IMRT).
High dose rate brachytherapy is an alternative form of radiation dose escalation for high risk disease, with the potential to improve long term local control in high risk prostate cancer.
A low dose rate brachytherapy implant has a similar 10-15 cancer specific survival to a radical prostatectomy for low risk, or low volume intermediate risk prostate cancer, with the potential for decreased risk of urinary incontinence and impotence.