Biochemical recurrence after prostatectomy: when to worry about PSA?

This article was translated from the original Portuguese. Português

Introduction

After radical prostatectomy, many patients expect their PSA to drop to zero. In most cases this happens: after complete removal of the prostate, PSA should fall to undetectable levels (< 0.03 ng/mL). However, in some men the marker starts rising again over months or years. This rise is called biochemical recurrence and indicates that active prostate cells remain, whether benign or malignant.

Understanding what this means, when to investigate and what the treatment options are is essential to act at the right time — neither too early nor too late.

Definition of biochemical recurrence

According to the EAU 2025 and NCCN 2025 guidelines, biochemical recurrence (BCR) is defined as:

• PSA ≥ 0.2 ng/mL on two consecutive measurements after surgery.

A single isolated value of 0.1 ng/mL does not constitute recurrence. The time between the nadir (lowest value) and the rise also matters: early rises (< 12 months) suggest aggressive disease, while late rises (> 3 years) tend to indicate local recurrence.

What can cause a detectable PSA after surgery

1. Benign remnants of prostate tissue (at the bladder margin or urethra).
2. Microscopic residual disease not visible at the time of surgery.
3. Local recurrence in the prostate bed.
4. Microscopic spread to lymph nodes or bone.

The challenge is to distinguish between these possibilities with as few unnecessary interventions as possible.

Factors that influence the risk of recurrence

• Gleason ≥ 8 or ISUP 4–5.
• Positive surgical margins.
• Extraprostatic extension (pT3) or seminal vesicle invasion (pT3b).
• Short PSA doubling time (PSADT) (< 6 months).

Patients with these factors warrant closer monitoring and may benefit from early salvage treatment.

A detectable PSA is not a sentence

About 20 to 30% of men show some rise in PSA after surgery (EAU 2025). However, not all of them progress to clinically significant disease. Studies by Pound et al., JAMA 1999 and Boorjian et al., Eur Urol 2020 show that many remain stable for years without needing further intervention.

Modern imaging tests

The major advance in early detection is PET-PSMA (Prostate-Specific Membrane Antigen). This scan identifies recurrences at very low PSA levels — from 0.2 ng/mL — and is more accurate than bone scintigraphy and conventional CT.

• Overall sensitivity: ~80% for PSA > 0.5 ng/mL.
• Detection of a single lesion (oligometastasis): up to 45% of cases (EAU 2025).

Combining PET-PSMA + pelvic MRI provides the most detailed map of residual disease and guides personalized treatment decisions.

Salvage treatments

1. Salvage radiotherapy (SRT):Indicated when PSA starts rising again, ideally before reaching 0.5 ng/mL.
   • Best results when given early (Trock et al., JAMA 2008).
   • Dose: 64–72 Gy to the prostate bed, with or without pelvic irradiation.
2. Short-term hormone therapy (ADT): Adding 6 to 24 months of androgen deprivation (LHRH analogues ± antiandrogens) increases the rate of biochemical control by up to 20% (RTOG 9601 – Spratt et al., NEJM 2017).
3. Salvage surgery (lymphadenectomy or local excision): Indicated only in specialized centers and in well-localized cases.
4. Modern systemic therapies: For confirmed metastatic disease: apalutamide, enzalutamide, abiraterone, darolutamide or lutetium-177 PSMA, depending on the clinical scenario.

The role of PSA doubling time (PSADT)

PSADT is calculated by comparing two to three serial measurements.

• < 3 months: high risk of metastasis and mortality.
• 3–12 months: intermediate risk.
• > 12 months: local recurrence likely, favorable prognosis.

This parameter is decisive in determining how urgently to intervene.

Follow-up after surgery

Recommended protocol (EAU 2025):

• PSA every 3 months in the 1st year.
• Every 6 months from the 2nd to the 5th year.
• Annually after 5 years, if stable.

No rise for more than 10 years indicates lasting remission.

Final message

A detectable PSA does not mean treatment has failed. It simply means it is time to investigate precisely. Thanks to PET-PSMA and early salvage radiotherapy, many patients are able to cure the recurrence before it spreads.

The key is to monitor regularly and discuss each result with your urologist — rationally, without alarm and without delay.

Key references

1. EAU Guidelines on Prostate Cancer 2025.
2. NCCN v2.2025 – Prostate Cancer.
3. Spratt DE et al., NEJM 2017; 376:417–428.
4. Trock BJ et al., JAMA 2008; 299:2760–2769.
5. Boorjian SA et al., Eur Urol 2020; 78:105–115.
6. Pound CR et al., JAMA 1999; 281:1591–1597.

Dr. Bruno Benigno | Urology, Oncology and Robotic Surgery – Clínica Uro Onco – São Paulo – SPwww.clinicauroonco.com.br | WhatsApp +55 (11) 99590-1506 – Instagram @dr_benigno

Dr. Bruno Benigno
Urologist and uro-oncologic surgeon (CRM-SP 126.265 · RQE 60022). More than 1,500 robotic surgeries. Member of the AUA, EAU and SBU. Meet Dr. Bruno · In the Media

This content is educational and does not replace a medical consultation. Each case must be assessed individually, based on AUA, EAU and NCCN guidelines.