Chris Parker, MD, consultant clinical oncologist, The Royal Marsden NHS Foundation Trust, discusses the optimal timing of salvage radiotherapy for men with prostate cancer.

The phase 3 RADICALS-RT trial evaluated the superiority of adjuvant radiotherapy versus salvage radiotherapy after radical prostatectomy. While adjuvant radiotherapy may be a more effective treatment, salvage radiotherapy can spare patients the toxicities associated with radiotherapy.

Salvage therapy should be implemented early for men who have recently undergone a radical prostatectomy rather than after they have a dramatic rise in their prostate-specific antigen (PSA), says Parker. Men should be considered for radiation as soon as their PSA begins to rise after surgery.

While PSA does not indicate which patients have prostate cancer, it serves as an early marker of recurrence in men who have undergone radical prostatectomy, explains Parker.

As such, rising PSA may indicate recurrence early enough that salvage radiotherapy can be curative, concludes Parker.

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Chris Parker, MD, discusses the optimal timing of salvage radiotherapy for men with prostate cancer.

Dr. Parker on the Optimal Timing of Salvage Therapy in Prostate Cancer

Chris Parker, MD, consultant clinical oncologist, The Royal Marsden NHS Foundation Trust, discusses the rationale for the phase III RADICALS-RT trial in prostate cancer. 

The RADICALS-RT study evaluated the superiority of adjuvant radiotherapy versus salvage radiotherapy after radical prostatectomy, explains Parker. 

There is some controversy regarding the timing of radiotherapy. Some believe that adjuvant radiotherapy should be given to men who have a risk of recurrence, whereas others recommend salvage radiotherapy for men who recur, says Parker.

 Adjuvant radiotherapy may be more effective because patients are exposed to therapy earlier on, explains Parker. Conversely, salvage radiotherapy spares men who do not recur after surgery the toxicities associated with radiotherapy, concludes Parker.

Chris Parker, MD, discusses the rationale for the phase III RADICALS-RT trial in prostate cancer.

Dr. Parker on the Rationale for the RADICALS-RT Trial in Prostate Cancer

Chris Parker, MD, consultant clinical oncologist, The Royal Marsden NHS Foundation Trust, discusses the results of the phase III RADICALS-RT trial in prostate cancer.

Historically, the optimal timing of radiotherapy after radical prostatectomy had not been well defined. To this end, investigators compared the efficacy of adjuvant radiotherapy versus observation and salvage radiotherapy in 1,396 patients who had undergone radical prostatectomy and had high-risk disease and rising prostate-specific antigen, respectively.

At a median follow-up of 5 years, the rate of biochemical progression-free survival was 85% versus 88% in the adjuvant and salvage radiotherapy arms, respectively (HR, 1.10; 95% CI, 0.81-1.49; 

 =.56). However, the 1-year rate of self-reported urinary incontinence was 5.3% and 2.7% in the adjuvant and salvage radiotherapy arms, respectively, suggesting that observation and salvage radiotherapy should be the standard approach, concludes Parker.

Dr. Parker on the Results of the RADICALS-RT Trial in Prostate Cancer

Chris Parker, MD, consultant clinical oncologist, The Royal Marsden NHS Foundation Trust, discusses the role of radiotherapy in metastatic prostate cancer.

Men with newly diagnosed metastatic prostate cancer have traditionally been treated with androgen deprivation therapy (ADT) or chemotherapy, says Parker. In terms of surgery and radiotherapy, these modalities are only used in the palliative setting. However, preclinical models have suggested that radiation to the primary cancer can slow down metastases and improve survival in patients.

In the STAMPEDE study presented at the 2018 ESMO Congress, patients were randomized to receive either ADT or ADT with radiation. While the addition of radiation seemed to have no immediate impact on the general cohort of patients, overall survival in a subgroup analysis of patients with a low metastatic burden was improved by 30%. Parker, lead author of the phase III study, concludes that radiotherapy should be a standard treatment option for these patients.

Chris Parker, MD, consultant clinical oncologist, The Royal Marsden NHS Foundation Trust, discusses the role of radiotherapy in patients with metastatic prostate cancer.

Dr. Parker on Radiotherapy in Metastatic Prostate Cancer

Chris Parker, MD, consultant clinical oncologist, The Royal Marsden NHS Foundation Trust, discusses the rationale for radiotherapy in the treatment of newly-diagnosed metastatic prostate cancer.

This subgroup of patients has always been managed with drug treatment, says Parker. They do not have specific treatment to the prostate, such as radiotherapy, unless they show symptoms. In some animal models, treating the primary cancer showed a slowing of metastasis, which improved survival. This hypothesis was then tested in a subgroup analysis from the STAMPEDE trial, where patients with newly-diagnosed metastatic prostate cancer with a low metastatic disease burden were given radiotherapy in addition to standard of care therapy.

Findings showed that men with low metastatic disease burden demonstrated a 32% improvement in overall survival (OS) when given radiotherapy plus standard of care therapy compared with men who received standard of care treatment alone. The absolute improvement in OS in this group at 3 years was 81%. However, OS was not improved with radiotherapy in the 1120 men with a higher metastatic burden.

Chris Parker, MD, consultant clinical oncologist, The Royal Marsden NHS Foundation Trust, discusses the rationale for radiotherapy in the treatment of newly-diagnosed metastatic prostate cancer.
 

Dr. Parker on the Rationale for Radiotherapy in Metastatic Prostate Cancer

Chris Parker, MD, consultant clinical oncologist, The Royal Marsden NHS Foundation Trust, discusses the role of radiotherapy in newly diagnosed prostate cancer.

Results from the STAMPEDE trial presented at the 2018 ESMO Congress showed that men with low metastatic disease burden who received radiotherapy plus standard of care had a 32% improvement in overall survival (OS) compared with men who received standard of care treatment alone.

In the prespecified subgroup analysis, radiotherapy to the prostate improved OS by 32% in the 819 men with a low burden of metastatic disease (HR 0.68, 95% CI 0.52-0.90). The absolute improvement in OS in this group at 3 years was 81%. Radiotherapy conferred no survival benefit in the men with a high metastatic disease burden, though.

Chris Parker, MD

Articles

Dr. Parker on the Optimal Timing of Salvage Therapy in Prostate Cancer

Dr. Parker on the Rationale for the RADICALS-RT Trial in Prostate Cancer

Dr. Parker on the Results of the RADICALS-RT Trial in Prostate Cancer

Dr. Parker on Radiotherapy in Metastatic Prostate Cancer

Dr. Parker on the Rationale for Radiotherapy in Metastatic Prostate Cancer

Dr. Parker on the Role of Radiotherapy in Newly Diagnosed Prostate Cancer