40 Participants Needed

Early vs Delayed Salvage Radiotherapy for Prostate Cancer

(TOPP Trial)

UofT Radiation Oncology Residents on X ...
Overseen BySrinivas Raman
Age: 18+
Sex: Male
Trial Phase: Phase 2
Sponsor: University Health Network, Toronto
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

The investigators will randomize patients presenting with early BCR with a negative baseline PSMA PET/CT, to upfront SRT or surveillance. Early BCR is defined as a PSA relapse of \>0.1 to \<0.3 ng/mL. Patients in the surveillance arm will be monitored with PSA every 3 months. A repeat PSMA PET/CT will be undertaken when the PSA reaches a target level of \>0.5 to \<1.0 ng/mL. Both early radiation treatment and surveillance with repeat PSMA PET/CT imaging are within patterns of practice locally; therefore, the investigators believe that there is clinical equipoise on this subject.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are using androgen deprivation therapy, you cannot participate in the trial.

What data supports the effectiveness of the treatment Salvage Radiotherapy for Prostate Cancer?

Research shows that salvage radiotherapy (SRT) can improve survival in prostate cancer patients who experience a rise in PSA (a protein that can indicate cancer activity) after surgery, without evidence of cancer spread. This approach may reduce side effects compared to immediate radiation after surgery, as it targets only those with signs of cancer returning.12345

Is salvage radiotherapy generally safe for humans?

Salvage radiotherapy (SRT) for prostate cancer has been studied for safety, showing some patients experience urinary and gastrointestinal side effects. In one study, 9% of patients had severe urinary issues, and 7% had moderate gastrointestinal issues, but severe gastrointestinal problems were rare.24678

How is salvage radiotherapy different from other treatments for prostate cancer?

Salvage radiotherapy (SRT) is unique because it is specifically used after prostate surgery (radical prostatectomy) to target any remaining cancer cells when prostate-specific antigen (PSA) levels rise, indicating a recurrence. Unlike initial treatments, SRT is applied when cancer returns, and its timing (early vs delayed) can impact its effectiveness.29101112

Eligibility Criteria

Men over 18 with prostate cancer who've had surgery (prostatectomy) and have a specific low PSA level indicating early recurrence, but no signs of cancer spread on advanced imaging. They must be in good physical condition and understand the study's risks.

Inclusion Criteria

I am fully active or can carry out light work.
I am 18 years old or older.
My cancer is in the early or locally advanced stage but hasn't spread to distant organs.
See 5 more

Exclusion Criteria

I cannot undergo radiotherapy due to other health issues.
I have had radiation therapy to my pelvic area before.
I am currently using or have used hormone therapy after prostate surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either early salvage radiotherapy or surveillance with delayed PSMA PET/CT imaging

Varies
Regular visits for radiotherapy or PSA monitoring every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years
PSA results every 3 months for surveillance patients

Treatment Details

Interventions

  • Salvage radiotherapy
Trial OverviewThe trial is testing two approaches after surgery: immediate radiotherapy or monitoring PSA levels closely and only using radiotherapy if PSA rises to a certain point. Patients are randomly assigned to one of these strategies.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: SurveillanceExperimental Treatment1 Intervention
Patients with early biochemical relapse of prostate cancer following radical prostatectomy who have a PSA greater than or equal to 0.1 to less than 0.3 ng/mL with negative PSMA PET/CT will go on surveillance. Routine PSA will be conducted and a repeat PSMA PET/CT imaging will be conducted when the PSA rises to greater than 0.5 to less than 1.0 ng/mL.
Group II: Salvage radiotherapyActive Control1 Intervention
Patients with early biochemical relapse of prostate cancer following radical prostatectomy who have a PSA of greater than or equal to 0.1 to less than 0.3 ng/mL with negative PSMA PET/CT will receive salvage radiotherapy to the prostate bed. This radiotherapy may or may not include the pelvic lymph nodes.

Salvage radiotherapy is already approved in United States, European Union, Canada for the following indications:

🇺🇸
Approved in United States as Salvage Radiation Therapy for:
  • Prostate cancer recurrence after prostatectomy
🇪🇺
Approved in European Union as Salvage Radiation Therapy for:
  • Prostate cancer recurrence after prostatectomy
🇨🇦
Approved in Canada as Salvage Radiation Therapy for:
  • Prostate cancer recurrence after prostatectomy

Find a Clinic Near You

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials
1,555
Recruited
526,000+

Findings from Research

In the SAKK 09/10 trial involving 350 men with biochemical progression of prostate cancer after surgery, conventional-dose salvage radiotherapy (64 Gy) was found to be equally effective as dose-intensified radiotherapy (70 Gy) in preventing further cancer progression, with similar freedom from biochemical progression rates (62% vs. 61%).
Higher doses of radiation (70 Gy) resulted in increased gastrointestinal toxicity without any significant improvement in clinical outcomes, suggesting that conventional-dose SRT is sufficient and safer for patients with early biochemical progression after radical prostatectomy.
Dose-intensified Versus Conventional-dose Salvage Radiotherapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: The SAKK 09/10 Randomized Phase 3 Trial.Ghadjar, P., Hayoz, S., Bernhard, J., et al.[2022]
In a study of 859 men who underwent radical prostatectomy and chose initial observation, those with positive surgical margins or extracapsular extension had a 7-year PSA progression-free survival rate of 62%, while those with seminal vesicle invasion had a lower rate of 32%.
For patients who experienced PSA progression and received delayed salvage radiation therapy (SRT), 56% of those with positive surgical margins or extracapsular extension maintained an undetectable PSA for 5 years, indicating that SRT can be an effective treatment strategy for selected patients.
Long-term rates of undetectable PSA with initial observation and delayed salvage radiotherapy after radical prostatectomy.Loeb, S., Roehl, KA., Viprakasit, DP., et al.[2015]
Early salvage radiotherapy (SRT) may be safer than adjuvant radiotherapy (ART) for prostate cancer patients after radical prostatectomy, as it targets only those with biochemical recurrence, potentially reducing side effects without compromising treatment outcomes.
The selection of patients for SRT and the timing of radiotherapy remain uncertain, highlighting the need for further research on the use of novel imaging techniques and genomic classifiers to optimize post-operative management.
Radiation Therapy After Radical Prostatectomy: What Has Changed Over Time?Zattoni, F., Heidegger, I., Kasivisvanathan, V., et al.[2021]

References

Dose-intensified Versus Conventional-dose Salvage Radiotherapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: The SAKK 09/10 Randomized Phase 3 Trial. [2022]
Long-term rates of undetectable PSA with initial observation and delayed salvage radiotherapy after radical prostatectomy. [2015]
Radiation Therapy After Radical Prostatectomy: What Has Changed Over Time? [2021]
The Effect of Salvage Radiotherapy and its Timing on the Health-related Quality of Life of Prostate Cancer Patients. [2019]
Salvage radiotherapy in prostate cancer patients with biochemical relapse after radical prostatectomy : Prolongation of prostate-specific antigen doubling time in patients with subsequent biochemical progression. [2018]
Integrating Prostate-specific Antigen Kinetics into Contemporary Predictive Nomograms of Salvage Radiotherapy After Radical Prostatectomy. [2022]
Impact of Dose Escalation on the Efficacy of Salvage Radiotherapy for Recurrent Prostate Cancer-A Risk-Adjusted, Matched-Pair Analysis. [2023]
Disease Control With Delayed Salvage Radiotherapy for Macroscopic Local Recurrence Following Radical Prostatectomy. [2023]
Impact of Early Salvage Radiation Therapy in Patients with Persistently Elevated or Rising Prostate-specific Antigen After Radical Prostatectomy. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
The timing of salvage radiotherapy after radical prostatectomy: a systematic review. [2022]
Outcomes of salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. [2018]
12.United Statespubmed.ncbi.nlm.nih.gov
Long-term Outcome of Prostate Cancer Patients Who Exhibit Biochemical Failure Despite Salvage Radiation Therapy After Radical Prostatectomy. [2021]