Detecting recurrent prostate cancer after definitive treatment remains one of the most challenging aspects of prostate cancer management. For men who undergo radical prostatectomy, a rising prostate-specific antigen (PSA) level—known as biochemical failure or biochemical recurrence—often serves as the first indication that cancer has returned. However, identifying the precise location of recurrent disease is critical, as it directly influences treatment decisions and patient outcomes.

New evidence suggests that when it comes to detecting local recurrence after prostatectomy, multiparametric magnetic resonance imaging (mpMRI) may outperform prostate-specific membrane antigen (PSMA) PET-CT, particularly at the prostate bed.

Understanding Biochemical Failure After Prostatectomy

Following radical prostatectomy, PSA levels should drop to undetectable levels. Any subsequent rise in PSA is considered biochemical recurrence and raises concern for residual or recurrent disease. This recurrence may be:

• Local, occurring in the prostate bed

• Regional, involving pelvic lymph nodes

• Distant, such as bone or visceral metastases

Accurately determining the site of recurrence is essential, as localized disease may be amenable to salvage radiation therapy, while more widespread disease often requires systemic treatment.

Imaging Options for Restaging Prostate Cancer

Two advanced imaging modalities are commonly used to restage patients with biochemical recurrence:

Multiparametric MRI (mpMRI)
mpMRI combines anatomical and functional imaging sequences—including T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement—to provide high-resolution visualization of soft tissue. It is particularly well suited for detecting subtle changes in the prostate bed following surgery.

PSMA PET-CT
PSMA PET-CT uses radiotracers that bind to prostate-specific membrane antigen, a protein highly expressed on prostate cancer cells. This modality has transformed prostate cancer imaging by enabling highly sensitive detection of nodal and distant metastatic disease, even at low PSA levels.

Key Findings From Recent Research

In patients with biochemical failure after prostatectomy, approximately two thirds were found to have detectable local disease at restaging, underscoring how common localized recurrence is in this setting.

The study revealed striking differences in detection rates between imaging modalities:

• Multiparametric MRI alone detected local recurrent lesions in more than one third of patients

• PSMA PET-CT alone identified local disease in only 5.9% of patients

These findings indicate that while PSMA PET-CT excels at identifying metastatic spread, it may miss small or early local recurrences confined to the prostate bed.

Why mpMRI Performs Better for Local Recurrence

Several factors explain the superior performance of mpMRI in detecting local disease:

• High spatial resolution allows for detailed visualization of the prostate bed and surrounding soft tissues

• Functional imaging sequences help differentiate scar tissue from recurrent tumor

• Sensitivity to small lesions that may not express enough PSMA to be detected by PET imaging

After prostatectomy, recurrent tumors may be small, infiltrative, and located near surgical margins, making them difficult to detect with molecular imaging alone.

Strengths and Limitations of PSMA PET-CT

Despite its lower sensitivity for local recurrence, PSMA PET-CT remains invaluable in other clinical scenarios. Its strengths include:

• Superior detection of lymph node involvement

• Early identification of bone and distant metastases

• Whole-body imaging in a single study

However, limitations include reduced sensitivity for microscopic local disease and potential false negatives in tumors with low PSMA expression.

Complementary, Not Competing, Modalities

Rather than viewing mpMRI and PSMA PET-CT as competing technologies, the study highlights their complementary roles. Combining both modalities may offer the most comprehensive assessment of recurrent prostate cancer:

• mpMRI excels at identifying local recurrence, guiding salvage radiation planning

• PSMA PET-CT helps detect regional and distant disease, influencing systemic therapy decisions

Using both imaging techniques strategically can improve staging accuracy and personalize treatment.

Clinical Implications for Patient Care

The findings have important implications for clinicians managing patients with biochemical recurrence after prostatectomy:

• mpMRI should be strongly considered when evaluating suspected local recurrence, even if PSMA PET-CT findings are negative

• Negative PSMA PET-CT does not rule out treatable local disease

• Accurate localization can enable earlier, targeted salvage therapy and potentially improve long-term outcomes

Looking Ahead

As imaging technology continues to evolve, optimizing the sequencing and combination of diagnostic tools will be essential. Ongoing research is exploring hybrid imaging approaches, such as PET-MRI, which may further enhance detection while reducing redundancy.

For now, the evidence suggests a clear message: when searching for prostate cancer recurrence after prostatectomy, multiparametric MRI remains a critical tool, particularly for identifying local disease that could otherwise go undetected.

Early and precise detection not only shapes treatment decisions—it may ultimately determine whether recurrence can be controlled or cured.