Radiation is the standard of care for the high-risk disease. There is level one evidence that radiotherapy can cure men with this type of disease. Modern treatment with brachytherapy boost has even better results than the using only external beam radiotherapy. Dr. Morton believes that performing prostatectomy increases morbidity without improving cure and should be considered only in select cases.
There are three important randomized controlled trials in the setting of locally advanced /high-risk disease comparing androgen deprivation therapy (ADT) to ADT + radiotherapy:
- The PR-3 trial1, which included 1206 patients
- The Scandinavian Prostate Cancer Group -7 trial2, which included 875 men
- The Mottet Trial3, which included 264 patients
Even radiotherapy with the older methods that were used in the past, demonstrates an improvement in survival, as seen in figure 1. Moreover, the just recently published STAMPEDE arm H trial4 demonstrated that radiotherapy improves survival even in low-burden metastatic prostate cancer patients (figure 2). A meta-analysis of patients with Gleason 8-10 prostate cancer from 6 randomized trials (RTOG 8531, 8610, 9202, EORTC 22863, 22961, 22991) was recently presented in ASTRO 2018.5 On multivariable analysis, local failure was strongly associated with distant metastases, prostate cancer survival, and overall survival. Late recurrence (>5 years) most commonly was associated with local failure.
Brachytherapy with boost has been shown to reduce late relapses in high-risk patients. A retrospective cohort comparing radical prostatectomy to external beam radiotherapy and external beam radiotherapy (EBRT) + brachytherapy boost was recently published, analyzing Gleason 9-10 patients.6 The results demonstrated that EBRT + brachytherapy was superior when compared to the other modalities (Figure 3) in prostate cancer-specific survival, and distant metastasis-free survival.
Figure 1 – Older Methods of Radiation Improve Survival in Prostate Cancer Patients:
Figure 2 – Radiotherapy Improves Survival in Patients With Low-Burden Metastatic Prostate Cancer:
Figure 3 – External Beam Radiotherapy with Brachytherapy Boost Improves Survival
According to Dr. Morton, most of the patients treated with radical prostatectomy will fail, even if the surgery is performed at a center of excellence. Radical prostatectomy adds morbidity without evidence of improved outcomes, compared to standard ADT + radiotherapy. In select patients, this procedure can be considered adequate. Retrospective studies comparing radical prostatectomy to radiotherapy have shown an advantage to surgery. However, these are prone to significant selection biases, with the patients with higher comorbidities usually selected to undergo radiotherapy. Moreover, when comparing the death rate of patients who underwent radical prostatectomy to patients who did not undergo this treatment, patients who underwent surgery were demonstrated to harbor lower death rates than the general population (SMR of 0.47), which means that these are highly selected patients, who are considerably healthier.7
In summary, Dr. Morton believes that ADT + RT (and especially EBRT + brachytherapy) is the standard of care for high-risk prostate cancer patients. Prostatectomy is an acceptable alternative for some patients, but has greater morbidity, with a high failure rate, that just delays the need for radiotherapy.
Presented by: Gerard Morton, MB, BCh BAO, MRCPI, FFRRCSI, FRCPC, Affiliate scientist, Odette Cancer Centre, Sunnybrook Health Science Center, Toronto, Ontario, Canada
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter: @GoldbergHanan at the CUOS – Canadian Uro-Oncology Summit 2019, #CUOS19 January 10-12, 2019 Westin Harbour Castle, Toronto, Ontario, Canada
1. Mason et al. JCO 2015
2. Fossa et al. Eur Urol 2016
3. Mottet et al. Eur Urol 2012
4. Parker et al, Lancet 2018
5. Kishan et al. ASTRO 2018
6. Kishan et al JAMA 2018
7. Eifler JB et al. J Urol 2012
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High-Risk Prostate Cancer Debate: Surgery