Short vs Long Course Radiotherapy for Prostate Cancer

(CONSORT-PC Trial)

Overseen By Peter Chung, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: ADT, ARAT

Disqualifiers: Prior pelvic radiotherapy, Ulcerative colitis, Crohn's, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, randomized phase II trial investigating if radiation treatment delivered every other day for 2 weeks has the same side effects as radiation treatment delivered once weekly for 6 weeks.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you can be on systemic treatment like ADT (androgen deprivation therapy) with or without ARAT (androgen receptor axis-targeted therapy), and previous chemotherapy is allowed if it was completed more than 6 weeks before joining the trial.

What data supports the effectiveness of the treatment for prostate cancer?

Research shows that external beam radiation therapy is effective for early-stage prostate cancer, with outcomes similar to surgery. It is considered a standard treatment for locally advanced prostate cancer, and new techniques are improving its effectiveness and reducing side effects. ^{1 2 3 4 5}

Is radiotherapy safe for treating prostate cancer?

Radiotherapy for prostate cancer is generally considered safe, with studies showing it is well-tolerated and has a low rate of severe side effects. Some patients may experience moderate complications, but these are relatively rare. ^{6 7 8 9 10}

How does radiotherapy for prostate cancer differ from other treatments?

Radiotherapy for prostate cancer, specifically external beam radiation therapy, is unique because it uses high-energy rays to target and kill cancer cells, and can be administered in different schedules, such as short or long courses. Unlike surgery or hormone therapy, it is non-invasive and can be combined with hormone therapy for enhanced effectiveness, especially in advanced cases. ^{2 11 12 13 14}

Eligibility Criteria

Men aged 18+ with metastatic prostate cancer, either low or high volume, are eligible. They must be fit for daily activities (ECOG 0 or 1), planning to receive external beam radiation therapy (EBRT) while on hormone therapy +/- ARAT. Prior chemotherapy is okay if it was over six weeks ago. Men with active inflammatory bowel disease or conditions that rule out radiotherapy, especially prior pelvic radiation, can't join.

Inclusion Criteria

I am scheduled for external beam radiation therapy.

My cancer has spread to other parts of my body, including possibly my bones or organs.

I am 18 years old or older.

Exclusion Criteria

I have a health condition that prevents me from receiving radiotherapy.

I have had radiation therapy to my pelvic area before.

My doctor confirms I have active ulcerative colitis or Crohn's Disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive radiation treatment. Arm 1: every other day for 2 weeks; Arm 2: once a week for 6 weeks

2-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Radiotherapy

Trial Overview This study compares two schedules of delivering radiation treatment for metastatic prostate cancer: one group will receive treatments every other day for two weeks and the other once weekly for six weeks. The goal is to see if side effects differ between these schedules.

Participant Groups

Group I: Arm 2 - Standard Experimental Treatment 1 Intervention

Radiation treatment (36 Gy in 6 fractions) to be delivered once a week over 6 weeks.

Group II: Arm 1 - Investigational Experimental Treatment 1 Intervention

Radiation treatment (36 Gy in 6 fractions) to be delivered every other day over 2 weeks (excluding weekends).

Radiotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in United States as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Canada as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Japan as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in China as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Switzerland as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

Management of high-risk prostate cancers remains debated due to the lack of randomized trials comparing surgery and radiotherapy, but long-term androgen deprivation therapy (at least 18 months) is recommended when using external beam radiotherapy.

Combining external beam radiotherapy with brachytherapy has shown improved biochemical control in trials, and while it hasn't impacted overall survival, large retrospective studies suggest it may enhance specific and overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of radiotherapy for high risk localized prostate cancers. Hennequin, C., Labidi, M., Quéro, L.[2021]

External beam radiation therapy is an effective treatment for organ-confined and early-stage prostate cancer, showing good biochemical and overall survival rates.

Advanced techniques like intensity-modulated and three-dimensional conformal radiotherapy provide better tumor control with fewer complications, making them preferable for intermediate- and high-risk patients compared to radical prostatectomy, although both treatments yield similar quality of life outcomes post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results after external beam radiation therapy for T1-T2 localized prostate cancer. Lagerveld, BW., Laguna, MP., de la Rosette, JJ.[2022]

In a study of 120 high-risk prostate cancer patients, those treated with definitive external-beam radiotherapy (ExRT) had significantly better biochemical failure-free survival (BFFS) compared to those who underwent radical prostatectomy (RP), with BFFS of 97.8 months versus 34.4 months, respectively.

Despite the differences in BFFS, the rates of distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) were similar between the two treatment groups, indicating that while ExRT may reduce the risk of biochemical failure, both treatments can achieve comparable long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive external-beam radiotherapy versus radical prostatectomy in clinically localized high-risk prostate cancer: a retrospective study. Andic, F., Izol, V., Gokcay, S., et al.[2020]

In patients with early-stage prostate cancer (stage A and B), external beam radiation therapy shows equivalent 10-year outcomes compared to radical prostatectomy, indicating its effectiveness as a treatment option.

For more advanced prostate cancer (stage C), external beam radiation has proven effective with long-term results from thousands of patients, establishing it as the standard treatment against which new therapies should be evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiation treatment for prostate cancer: still the gold standard. Hanks, GE.[2007]

In a study of 54 patients under 60 years old with early-stage prostate cancer, external beam radiation therapy showed similar rates of local and metastatic control compared to older patients (60-70 years old), indicating its efficacy in younger patients.

Patients with locally advanced node-negative prostate cancer had poorer outcomes in local control and survival compared to those with early-stage disease, suggesting that treatment strategies may need to be adjusted for better management of advanced cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy for prostatic cancer: patient selection and the impact of local control. Kaplan, ID., Cox, RS., Bagshaw, MA.[2019]

In a study of 173 patients with high-risk localized prostate cancer, long-term androgen deprivation therapy (ADT) for 36 months or more combined with external-beam radiotherapy (EBRT) significantly improved five-year progression-free survival rates (92.8%) compared to short-term ADT (72.9%).

Patients receiving short-term ADT experienced a higher incidence of cardiovascular toxicity (grade II or above) compared to those on long-term ADT, indicating that longer ADT may not only enhance survival but also have a more favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the duration of hormonal therapy following radiotherapy for localized prostate cancer. Okubo, M., Nakayama, H., Itonaga, T., et al.[2022]

In a Phase II trial involving 138 patients with localized prostate cancer, the combination of external-beam radiation therapy and low-dose-rate permanent brachytherapy showed an 8-year biochemical control rate of 82% to 79%, indicating durable effectiveness in managing the disease.

However, the study reported a significant late toxicity rate, with 15% of patients experiencing severe genitourinary or gastrointestinal side effects, and 42% reporting grade 3 impotence, suggesting a need for improved strategies to minimize damage to healthy tissues during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of an RTOG Phase II trial (00-19) of external-beam radiation therapy combined with permanent source brachytherapy for intermediate-risk clinically localized adenocarcinoma of the prostate. Lawton, CA., Yan, Y., Lee, WR., et al.[2018]

In a study of 205 patients with local prostate cancer treated with megavoltage radiation, the local control rates were high, with 96% for stage A2, 94% for stage B, and 90% for stage C, indicating effective treatment across different cancer stages.

The overall survival rate was 71% and the disease-free survival rate was 60% over a median follow-up of 9.4 years, with only a low incidence of complications (0.5% requiring surgery), suggesting that radiation therapy is a safe and effective option for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate cancer: results of external irradiation. Reddy, EK., Krishnan, L., Giri, S., et al.[2018]

In a study of 7661 men with nonmetastatic prostate cancer who received radiotherapy, only 6.5% experienced complications within 30 days, indicating that short-term complications are relatively uncommon after this treatment.

Older age was linked to a higher risk of certain complications, but overall complication rates after radiotherapy were lower compared to those who underwent radical prostatectomy, suggesting that radiotherapy may be a safer option for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Major 30-day complications after radical radiotherapy: a population-based analysis and comparison with surgery. Alibhai, SM., Leach, M., Warde, P.[2009]

External beam radiation therapy for localized prostate cancer shows a high disease-free survival rate of nearly 80% at 5 years and 53% at 10 years, particularly for cancer confined to the prostate.

The treatment is well tolerated with a low rate of severe side effects, making it a viable option compared to radical prostatectomy, especially considering the prognostic factors analyzed in the study of 431 patients over a median follow-up of 4 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy of localized prostate cancer. Landmann, C.[2006]

The triple-course external beam irradiation technique for localized prostate cancer resulted in a high clinical local control rate of 96% and an 86% negative biopsy rate among treated patients, indicating effective treatment outcomes.

While 96% of patients experienced mild to moderate bladder and bowel reactions, only 2% had severe complications, suggesting that this treatment method is associated with minimal acute morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple course external beam radiotherapy for carcinoma of the prostate. El-Mahdi, AM., Turalba, CI., Schellhammer, PF., et al.[2019]

Combining androgen suppression therapy with external-beam radiation therapy has become the standard treatment for men with locally advanced prostate cancer, significantly improving outcomes such as disease control and survival rates.

Hormonal therapy should be started before radiation and continued throughout the treatment, with recent studies showing that shorter courses of hormone therapy (4 to 6 months) can be effective, challenging the previous belief that longer courses were always necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy combined with hormone therapy for prostate cancer. Lee, AK.[2007]

External beam radiotherapy (RT) has evolved significantly over the past 50 years, with modern techniques greatly improving its effectiveness in treating prostate cancer, thanks to advancements in computer and imaging technologies.

The review highlights the importance of predictive factors in determining the outcomes of external beam RT, whether used alone, in combination with androgen suppression, or as a postoperative treatment, emphasizing its role in contemporary patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiotherapy as curative treatment of prostate cancer. Pisansky, TM.[2013]

Hypofractionated radiotherapy, which delivers higher doses per session than conventional methods, may offer enhanced anti-tumor efficacy and a shorter treatment duration for prostate cancer, based on a systematic review of five randomized trials and thousands of patients.

Current evidence suggests that while hypofractionation could be a promising alternative to traditional radiotherapy, further results from ongoing randomized trials are needed before making changes to standard treatment practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of hypofractionated radiotherapy in the treatment of prostate cancer: a review]. Toledano, A., Beley, S., Bollet, M., et al.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

Role of radiotherapy for high risk localized prostate cancers. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Long-term results after external beam radiation therapy for T1-T2 localized prostate cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Definitive external-beam radiotherapy versus radical prostatectomy in clinically localized high-risk prostate cancer: a retrospective study. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

External beam radiation treatment for prostate cancer: still the gold standard. [2007]

5. United States pubmed.ncbi.nlm.nih.gov

Radiotherapy for prostatic cancer: patient selection and the impact of local control. [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Impact of the duration of hormonal therapy following radiotherapy for localized prostate cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Long-term results of an RTOG Phase II trial (00-19) of external-beam radiation therapy combined with permanent source brachytherapy for intermediate-risk clinically localized adenocarcinoma of the prostate. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Prostate cancer: results of external irradiation. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Major 30-day complications after radical radiotherapy: a population-based analysis and comparison with surgery. [2009]

10. France pubmed.ncbi.nlm.nih.gov

Radiation therapy of localized prostate cancer. [2006]

11. United States pubmed.ncbi.nlm.nih.gov

Triple course external beam radiotherapy for carcinoma of the prostate. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Radiation therapy combined with hormone therapy for prostate cancer. [2007]

13. England pubmed.ncbi.nlm.nih.gov

External beam radiotherapy as curative treatment of prostate cancer. [2013]

14. France pubmed.ncbi.nlm.nih.gov

[Role of hypofractionated radiotherapy in the treatment of prostate cancer: a review]. [2018]