Understanding Biochemical Recurrence in Localized Prostate Cancer with Dr Steve Freedland

[marnieg46]

Another highly entertaining and informative podcast from GU Cast. Hosts Prof. Declan Murphy and Dr Renu Eapen are joined by urologist and prostate cancer researcher Dr Steve Freedland - a world renowned urologist and researcher specialising in prostate cancer and BCR management. Dr Freedland is a professor at Cedars-Sinai and Duke University, with extensive research contributions in prostate cancer outcomes, ADT side effects and novel treatment options.

The discussion focusses on biochemical recurrence (BCR) in localised prostate cancer, covering risk factors, diagnosis, management options, and patient counselling. Dr Freedman also discusses the landmark series from John-Hopkins Medical Institute (links below) which is still considered as the best guide to the natural history of BCR after radical prostatectomy. And the key message that PSA doubling time is the most important tool to risk stratify patients remains true today.

Dr Freedman is the lead investigator of the EMBARK trial, published in NEJM in 2023 which has led to a new standard of care for men experiencing high-risk BCR after surgery or radiotherapy. EMBARK has clearly shown that the use of enzaluamide, either on its own, or with ADT, reduces the risk of metastases when compared with ADT alone.

Once again in GU Casts, the informal discussion moves beyond the specific title and there's usually something useful and of relevance for everyone regardless of stages. As these podcasts can only be posted on this site so if you do watch and recognise how helpful the discussion might be to others, I urge you to send them the link.

Key Takeaways from Dr Steve Freedland

✅ Not all BCR cases require immediate treatment - risk stratification is key

✅ PSA kinetics (doubling time, velocity) guide decision-making more than absolution PSA values

✅ Early salvage therapy improves outcomes but should be personalised to the patient

✅ PSMA PET imaging is revolutionising recurrence detection and treatment planning.

Key Topics Covered

1. What is Biochemical Recurrence?

Definition: A rise in PSA levels after curative treatment (surgery or radiation) without clinical or radiological evidence of metastatic disease.

Why it matters: While not always leading to metastasis, BCR can indicate prostate cancer progression, prompting treatment decisions.

2. Risk Factors & Predictors of BCR

Dr Freedland discusses key patient-specific and tumor-related factors influencing recurrent risk:

PSA Dynamics: PSA doubling time (PSADT) and absolute PSA levels.

Pathology Factors:

Gleason Score (>7 carries higher risk).

Surgical margin status (positive margins increase recurrence risk).

Extra-capsular extension and seminal vesicle invasion.

Time to Recurrence:

Early recurrence (within 2-3 years post treatment) suggests higher-risk disease.

Late recurrence may have a slower progression.

3. How is BCR Diagnosed?

Regular PSA Monitoring is the corner stone of BCR detection

PSA Thresholds for Recurrence:

After radical prostatectomy (RP) BCR is typically defined as PSA >0.2 ng/mL on two consecutive

tests.

After radiation therapy (RT) is defined by the Phoenix definition (PSA nadir +2.0 ng/mL.

Role of Advanced Imaging

PSMA PET scans.

MRI for local recurrence assessment assessment.

4. Treatment Strategies for BCR

Salvage therapy options depending on prior treatment history and risk stratification

A. Salvage Radiotherapy (SRT) for Post-Surgery BCR.

Best outcomes when PSA is <0.5 ng/mL at the time of treatment.

Adjuvant androgen deprivation therapy (ADT) may improve outcomes in high-risk cases.

B. Salvage Surgery for Post-Radiation BCR

Salvage prostatectomy is an option but carries significant morbidity

Focal therapies HIFU (high intensity focused ultrasound) or cryotherapy are emerging options.

C. Systemic Therapy Considerations

ADT: Standard for patients with high-risk BCR (short-term vs long-term).

Novel Agents: Role of second-generation antiandrogens (eg apalutamide, daralutamide,

enzalutamide) in select cases.

5. When to Treat vs When to Observe?

Indolent BCR cases (slow PSA rise, long PSADT) may be monitored with active surveillance.

Aggressive cases (rapid PSA doubling time <6 months, high risk pathology) require earlier

intervention.

6. Patient Counselling and Quality of Life Considerations

Balancing treatment risks (urinary, sexual and metabolic side effects) with benefits.

Discussing patient goals, anxiety and expectations regarding recurrence and progressing risks.

youtu.be/gQwx_fZNWGk(Not working as expected?)

Links:

Freedland et al JAMA 2005 jamanetwork.com/journals/jama...

EMBARK paper in NEJM nejm.org/doi/full/10.1056...

[MateoBeach]

Wow Marnie. Brava! That is such an excellent and detailed summary of this important body of knowledge. Well written and perfectly organized. I’m very impressed, my friend. -P

[petabyte in reply to MateoBeach]

Seconded!

I just finished watching. Towards the end (29:40) he mentioned they are waiting on trial data for RT patients as well.

[marnieg46 in reply to petabyte]

You could send that question to Declan perhaps via the comments section on YouTube. He's always very gracious providing information. I'll re-watch it and see if I can pick up a reference to the trial.

[petabyte in reply to marnieg46]

When I rewatched I'm guessing it is more data from the embark trial itself.

[marnieg46 in reply to MateoBeach]

Well my friend I definitely can't take credit for the content. It was supplied by Declan who is always appreciative of the opportunity to have a wider coverage of the information. I don't think I can post podcasts on APC unfortunately because many times the content, especially ones from Peter Mac, is somewhat more applicable to readers on that hub. Pity. Take good care, We'll talk soon 😊

[jdfamily]

Marnie, not sure if this will be of any benefit to you but wanted to share. I had prostrate cancer three years ago and had prostrate surgery. Approximately a year later my psa again began to rise. I had 38 sessions of radiation which dramatically reduced my psa. The radiation sessions went well after the first anxiety over the process. My experience with radiation was positive and side effects were minimal with mostly fatigue during and for several weeks after the sessions were complete. No living my life in three month increments as I monitor psa levels and meet with my oncologist then. Hope this was beneficial.

[ron_bucher in reply to jdfamily]

You might be interested in my Bio. My salvage radiation without any ADT gave me 7.5 years of undetectable PSA. My oncologist started using the "cure" word after about 6 years. I hope you have even better success!

I too initially had a lot of anxiety when I got the BCR. Effexor fixed my anxiety. My second BCR is when I began to think systemic treatments were my future. But with the advent of PSMA scans, I'm drug free with undetectable PSA again.

[ron_bucher]

"PSMA PET imaging is revolutionising recurrence detection and treatment planning. "

Exactly what Dr. Michael Steinberg and Dr. Mark Scholz discussed and emphasized so optimistically on oligometastatic cases in the 3/29/25 PCRI conference (even using the "cure" word!).

pcri.org/

I hope doctors who advise delaying treatment for BCR at the same time mention that delay is also a roll of the dice and not completely free of risk.