New guidelines around PSA testing promise to transform prostate cancer outcomes in Australia. The guidelines, which recommend that asymptomatic men between the ages of 50-69 are offered PSA testing every two years1, replace US Preventative Services Task Force guidelines and previous differing guidelines in Australia that some urologists blame for an increase in presentations with metastatic prostate cancer2. Certainly, when screening was discouraged, adverse consequences followed, with evidence showing that mortality from prostate cancer is lower when men are screened for it3. With prostate cancer the third most common cause of male cancer deaths in Australia, policies that improve early diagnosis can only help reduce mortality.

Yet efforts to improve outcomes require a similar focus on treatment. With choice now a key component of patient-centred care, we’re fortunate to have multiple treatment options for prostate cancer – but we could arguably do more to ensure newly-diagnosed patients understand the full range. For many, these options will include brachytherapy – an efficacious equivalent to traditional treatments4 that can yield important advantages in quality of life, convenience and patient experience. Despite these advantages, awareness and use of brachytherapy remains low. It’s a missed opportunity. However, with the new guidelines giving GPs a more active role in early diagnosis, physicians have the chance to harness their trusted relationship with patients and help them make fully-informed decisions about their care.

Complex choice

The choice of treatment for localised prostate cancer can certainly be complex, influenced by factors like age and co-morbidity, cancer characteristics, treatment availability and personal preferences. A fundamental principle is for patients to be given comprehensive information, access to multi- disciplinary input and psycho-social support during the decision-making process. Whilst there are various models whereby this may be achieved, the GP plays an integral role in all of them.

The USANZ recommends giving patients the opportunity to see a radiation oncologist for an opinion on all available treatment options5. The RANZCR’s Target Cancer campaign cites GPs as the best means of facilitating this at the referral stage. In addition, Optimal Care Pathways guidelines provide detailed information on the holistic approach to cancer care6, whilst PCFA Prostate Cancer Support Nurses provide further resources to support patients’ decision-making. We must maximise all these resources to help patients make informed choices.

Brachytherapy: underused

Active Surveillance is now an option for patients with early stage prostate cancer but if he desires radical treatment or has more aggressive disease, surgery (radical prostatectomy (RP) or robotic radical prostatectomy), remains the most common primary treatment for prostate cancer. Alongside it, external beam radiation (EBRT) and brachytherapy complete the range of options. However, despite brachytherapy being an alternative for many patients – it’s an unsung option that often goes under the radar.

Brachytherapy achieves high precision, targeted radiotherapy, using computerised treatment planning and image-guided delivery systems to deliver a tailored ablative tumour dose to the prostate whilst sparing surrounding organs. There are two techniques; low-dose rate (LDR), where radioactive seeds are permanently implanted into prostate tissue, and high-dose rate (HDR), where the radioactive source is temporarily placed into the prostate via implanted needles. Brachytherapy can be used as a monotherapy or in combination with EBRT.

LDR monotherapy

Established and emerging evidence supports a wider use of monotherapy brachytherapy. A 2012 comparative effectiveness study by the Prostate Cancer Study Group evaluated more than 50,000 patients with low, intermediate and high-risk disease treated with all available primary treatment options4,7. It found LDR monotherapy brachytherapy an excellent alternative to surgery in patients with low-risk and favourable intermediate-risk prostate cancer. Low-risk patients treated with LDR monotherapy demonstrated PSA recurrence-free survival (RFS) rates similar to those for EBRT and RP; long-term biochemical RFS reported at 89% at 12 years8. LDR monotherapy brachytherapy has also proven to be a good option in patients with selected favourable intermediate-risk disease, once again indicating durable PSA RFS; long-term biochemical RFS reported at 78% at 12 years8.

Recent local data show the positive effects of LDR monotherapy in clinically localised, low-to- intermediate-risk prostate cancer in a community setting – reporting excellent rates of biochemical RFS and overall survival (OS)9. The study, which evaluated 371 patients treated with LDR monotherapy between 2004-2011 and included a significant TURP cohort, reported OS of 96% with a median follow- up time of 5.5 years, with 98% followed up for at least 4 years. The 5-year biochemical RFS for the entire cohort was 95%9.

Better experience

LDR and HDR brachytherapy present a reduced risk of sexual side effects when compared with EBRT and RP. The recent ProtecT study showed the risk of incontinence following radiotherapy to be less than active surveillance. Data indicate that with brachytherapy, the risk of incontinence is less than 1%9,10, although short-term irritative or obstructive urinary symptoms may occur. Brachytherapy is also associated with shorter recovery times compared to surgery, and offers significantly reduced overall treatment times compared to EBRT11 meaning it interferes less with patients’ lives.

Combination brachytherapy

Brachytherapy may also have a role in intermediate and high-risk prostate cancer. The ASCENDE-RT trial found that an LDR brachytherapy boost in combination with EBRT is superior to a dose-escalated EBRT boost and shows a significant increase in survival rates12.

Overall survival rates are important in the evaluation of brachytherapy – a key component in the rebuttal of a misconception that may have held back its use. The inference that surgery is never an option in the event of brachytherapy failure may be inaccurate. Robotic salvage prostatectomy appears to be a reliable treatment with good oncological outcomes and acceptable continence rates for selected patients13. On the rare occasions that brachytherapy is unsuccessful, surgery remains a distinct possibility.

Another primary option

There’s little doubt the evidence-base supports the greater consideration and use of brachytherapy as a primary treatment option. With rural centres increasingly offering these services, access is no longer a barrier. Elsewhere in the world, regulators are using this evidence to expand their guidelines on the use of brachytherapy. A recent example has seen Cancer Care Ontario use the latest evidence to recommend LDR and HDR brachytherapy both as a monotherapy and a boost in combination with EBRT in defined eligible patient groups14.

The challenge for Australian healthcare is to cement brachytherapy as a primary consideration alongside RP and EBRT. GPs can play a major role in achieving this by helping patients understand the full range of treatment options and the associated implications for RFS, OS and quality of life. Fundamentally, it’s incumbent on all of us to ensure patients are empowered to make informed choices. As the burden of prostate cancer increases in Australia, GPs can be much more than referrers – they can open crucial dialogue that enhances decision-making and drives better outcomes.

References

1. Cancer Council Australia. Prostate Cancer Foundation of Australia and Cancer Council Australia PSA Testing Guidelines Expert Advisory Panel. Clinical practice guidelines PSA Testing and Early Management of Test- Detected Prostate Cancer. [Version URL: http://wiki.cancer.org.au/australiawiki/index.php?oldid=122819 http://wiki.cancer.org.au/australia/Guidelines:PSA_Testing/Summary_of_recommendations
2. Pain, C. PSA guidelines linked to metastatic disease. Medical Observer. March 2017. [Version URL: www.medicalobserver.com.au/medical-news/oncology/psa-guidelines-linked-to-rise-in-metastatic-disease cited 2017 May 20]
3. Prostate Cancer Diagnoses Fall as Use of PSA Test Declines – Medscape – May 23, 2017. [http://www.medscape.com/viewarticle/880457]
4. Grimm PD, Billiet I, Bostwick D et al. Comparative analysis of prostate specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int 2012; 109(Suppl 1): 22–29
5. http://www.prostate.org.au/awareness/for-healthcare-professionals/clinical-practice-guidelines-on-psa-testing/
6. http://www.cancerpathways.org.au/
7. Chao, MWT, Grimm P et al. Brachytherapy: state-of-the-art radiotherapy in prostate cancer. BJU Int 2015; 116, Supplement 3, 80–88
8. Potters L, Morgenstern C, Calugaru E et al. 12-year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urol 2005; 173: 1562–1566
9. Spencer S, Chao M, et al. Analysis of LDR outcomes in clinically localised prostate cancer incorporating a significant TURP cohort: A Community Experience. Abstract accepted for Presentation at ASTRO 2017.
10. Stone and Stock. Long-Term Urinary, Sexual, and Rectal Morbidity in Patients Treated with Iodine-125 Prostate Brachytherapy Followed Up for a Minimum of 5 Years. Urology. 2007 Feb;69(2):338-42.
11. Ferrer M, Suarez JF, Guedea F et al. Health-related quality of life 2 years after treatment with radical prostatectomy, prostate brachytherapy, or external beam radiotherapy in patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 2008; 72: 421–32
12. Morris W. James et al. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low- Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer. International Journal of Radiation Oncology • Biology • Physics , Volume 98 , Issue 2 , 275 – 285
13. Orre M, Piechaud T et al. Oncological and functional results of robotic salvage radical prostatectomy after permanent brachytherapy implants. Cancer Radiother. 2017 Apr 21(2):119-123
14. Chin J, Rumble RB et al. Brachytherapy for Patients With Prostate Cancer: American Society of Clinical Oncology/Cancer Care Ontario Joint Guideline Update. American Society of Clinical Oncology. May 2017. J Clin Oncol 35:1737-1743.