When PSA Rises but Bone Scan Is Negative: The Critical Role of 18F-FDHT PET/CT in Re-staging Advanced Prostate Cancer

 

Clinical Hook

An 86-year-old man had already endured years of treatment for advanced prostate cancer. His prostate-specific antigen (PSA) level began to rise again despite ongoing luteinizing hormone-releasing hormone (LHRH) agonist therapy. Surprisingly, the bone scan showed no evidence of metastatic disease.

For many clinicians, a normal bone scan might appear reassuring. Yet the patient's biochemical profile suggested otherwise. Was this simply biochemical recurrence, or was metastatic disease hiding beyond the limits of conventional imaging?

A subsequent 18F-FDHT PET/CT answered that question decisively. The examination revealed extensive lymph node metastases above and below the diaphragm, multiple skeletal metastases, and high androgen receptor (AR) expression throughout the metastatic lesions. Based on these findings, the patient's treatment strategy changed from continued hormonal suppression alone to consideration of androgen receptor antagonist therapy.

This case illustrates one of the most important lessons in modern prostate cancer imaging: molecular imaging can redefine disease burden even when conventional imaging appears normal.


Learning Objectives

After reading this article, readers should be able to:

  1. Explain the clinical purpose of prostate cancer re-staging.
  2. Understand the biological basis of 18F-FDHT PET/CT.
  3. Differentiate molecular imaging from conventional bone scintigraphy.
  4. Interpret the radiologic significance of androgen receptor imaging.
  5. Recognize how imaging findings influence systemic treatment decisions.
  6. Appreciate the future role of AI-assisted molecular imaging in precision oncology.

1. Anatomy Review

Understanding the Prostate and Androgen Receptor Biology

The prostate is an androgen-dependent gland located inferior to the urinary bladder and anterior to the rectum. Its development, physiological function, and malignant transformation are strongly influenced by androgen receptor signaling.

Although localized prostate cancer initially remains confined within the prostatic capsule, advanced disease frequently spreads through predictable anatomical pathways:

  • Pelvic lymphatic chains
  • Retroperitoneal lymph nodes
  • Axial skeleton
  • Vertebral venous plexus
  • Pelvic bones
  • Ribs
  • Sternum
  • Scapula

These metastatic routes closely match the distribution observed in the present case, where metastatic lesions involved lymph nodes both above and below the diaphragm as well as multiple skeletal sites.


Why Does Prostate Cancer Prefer Bone?

Unlike many solid tumors, prostate cancer demonstrates a strong affinity for bone tissue.

Several biological mechanisms contribute:

  • Chemokine-mediated homing
  • Osteoblast activation
  • Bone marrow microenvironment
  • Androgen receptor signaling
  • Tumor-induced bone remodeling

This interaction explains why skeletal metastases are common even before structural bone destruction becomes apparent.


Figure 1. Anatomy of Metastatic Spread in Advanced Prostate Cancer

Illustration demonstrating the prostate gland, pelvic lymphatic drainage, vertebral venous plexus, and typical skeletal metastatic distribution involving the vertebrae, pelvis, ribs, sternum, and scapula.


2. Case Presentation

Patient History

An 86-year-old man had previously been diagnosed with advanced prostate cancer.

Clinical characteristics included:

  • Clinical stage: cT4N0M0
  • Gleason score: 10
  • PSA: 120 ng/mL
  • Ongoing LHRH agonist therapy

Despite hormonal treatment, PSA levels remained markedly elevated, prompting further evaluation for disease progression.


Symptoms

The case file primarily highlights biochemical progression rather than symptom-driven recurrence. Rising PSA prompted reassessment of disease status.


Physical Examination

The source document does not describe physical examination findings.


Clinical Question

The key clinical question was straightforward:

Does rising PSA represent occult metastatic disease despite a normal bone scan?

This question led directly to molecular imaging with 18F-FDG PET/CT.


Laboratory Findings

ParameterResult
PSA120 ng/mL
Gleason Score10
Clinical StagecT4N0M0

These findings classify the patient as a very high-risk individual according to the case description.


CT Findings

The uploaded case presents CT findings as part of PET/CT fusion imaging rather than standalone diagnostic CT. Anatomical localization of metastatic lymph nodes and skeletal lesions was achieved through image fusion.


PET Findings

18F-FDHT PET/CT demonstrated:

  • Extensive supradiaphragmatic lymph node metastases
  • Extensive infradiaphragmatic lymph node metastases
  • Multiple skeletal metastases
  • High tracer uptake within metastatic lesions
  • Uniformly elevated androgen receptor expression

These findings were not detected on bone scintigraphy.


Pathology

The uploaded source does not provide histopathological findings beyond the established diagnosis of prostate cancer.


Final Diagnosis

Advanced prostate cancer with widespread androgen receptor-positive lymph node and skeletal metastases detected by 18F-FDHT PET/CT during re-staging.


Why Did PET/CT Detect Disease That Bone Scan Missed?

One of the educational highlights of this case is the biological difference between imaging modalities.

Bone scintigraphy visualizes osteoblastic activity, meaning it detects the bone's reaction to tumor invasion rather than the tumor itself.

In contrast, 18F-FDHT PET/CT images androgen receptor expression within tumor cells. Consequently, metastatic lesions may become detectable before sufficient bone remodeling occurs to produce a positive bone scan. This distinction explains why the uploaded case demonstrated extensive metastatic disease on FDHT PET/CT despite a negative bone scan.

3. Pathophysiology

Why Does Prostate Cancer Become Resistant to Hormonal Therapy?

For decades, androgen deprivation therapy (ADT) has been the cornerstone of treatment for advanced prostate cancer. Most prostate cancers initially depend on androgen receptor (AR) signaling for cellular proliferation, survival, and metastatic progression. By suppressing circulating testosterone using luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, clinicians can effectively inhibit tumor growth during the hormone-sensitive phase.

The patient in this case had already undergone LHRH agonist therapy, yet his PSA continued to rise, indicating progression despite androgen suppression. This clinical scenario prompted re-staging with molecular imaging.


Molecular Mechanisms of Castration Resistance

The uploaded case explains that prostate cancer cells can acquire several adaptive mechanisms that allow continued growth under low-androgen conditions:

  • Androgen receptor (AR) amplification
  • AR mutation
  • AR overexpression

These molecular alterations enable persistent activation of androgen signaling despite androgen deprivation and contribute to the development of castration-resistant prostate cancer (CRPC).

From a clinical perspective, these changes are highly relevant because 18F-FDHT PET/CT does not simply depict tumor burden—it visualizes androgen receptor expression, providing functional information that may influence therapeutic decision-making.


Imaging–Pathophysiology Correlation

One of the major educational messages of this case is the distinction between structural and molecular imaging.

Bone scintigraphy reflects osteoblastic activity, whereas 18F-FDHT PET/CT reflects androgen receptor biology. Consequently:

  • Bone remodeling may not yet be detectable on bone scan.
  • Tumor cells with active AR signaling can already demonstrate increased FDHT uptake.
  • Molecular abnormalities therefore become visible before substantial skeletal remodeling occurs.

The uploaded case explicitly highlights this concept by explaining why PET/CT detected metastatic disease that bone scintigraphy failed to identify.


Figure 2. Biological Basis of 18F-FDHT PET Imaging

Illustration demonstrating androgen receptor activation within prostate cancer cells, cellular uptake of 18F-FDHT, nuclear receptor binding, downstream signaling, and metastatic progression.


4. Epidemiology

Although this case concerns a single patient, the uploaded document provides several epidemiologic characteristics of advanced prostate cancer.

Table 1. Epidemiologic Characteristics of High-Risk Prostate Cancer

VariableSummary
Disease frequencyOne of the most common malignancies in men
Peak ageIncidence increases markedly in older adults
High-risk age group≥75 years
Major risk indicatorsElevated PSA, Gleason score ≥8, T3 or higher stage, lymph node involvement
Present case86-year-old man, Gleason score 10, PSA 120 ng/mL

These features classify the patient as belonging to a very high-risk category, consistent with the uploaded case.


5. Clinical Presentation

Early Clinical Features

According to the source document, early prostate cancer is frequently asymptomatic. As disease progresses, patients may develop:

  • Urinary difficulty
  • Increased urinary frequency
  • Hematuria
  • Bone pain
  • Weight loss

Importantly, biochemical recurrence may occur before overt clinical symptoms become evident, making serial PSA monitoring essential.


Laboratory Abnormalities

The most significant laboratory abnormality in this case was persistent PSA elevation despite ongoing androgen deprivation therapy.

This biochemical progression prompted additional molecular imaging rather than reliance on conventional imaging alone.


Clinical Red Flags

Based on the uploaded case, clinicians should consider advanced imaging when encountering:

  • Rising PSA after treatment
  • Biochemical recurrence
  • Failure of hormonal therapy
  • Discordance between laboratory findings and conventional imaging

These situations are specifically identified as important indications for re-staging.


6. Imaging Features

Expert Radiologist Interpretation

This section follows the structure routinely used in subspecialty radiology practice. Interpretations below are based on the imaging descriptions provided in the uploaded case rather than direct review of the original images.


Figure 3. Maximum Intensity Projection (MIP)

Whole-body 18F-FDHT PET maximum intensity projection demonstrates increased radiotracer uptake involving lymph nodes above and below the diaphragm together with multifocal skeletal metastases.


Radiologist Interpretation

Imaging Technique

  • Whole-body 18F-FDHT PET/CT
  • Maximum Intensity Projection (MIP)

Distribution

Multiple foci of increased radiotracer uptake are present throughout:

  • Supradiaphragmatic lymph nodes
  • Infradiaphragmatic lymph nodes
  • Axial skeleton

The distribution strongly favors disseminated metastatic disease.

Biological Interpretation

Rather than indicating osteoblastic response, tracer accumulation reflects high androgen receptor expression within metastatic lesions.


Clinical Imaging Interpretation

The MIP image rapidly communicates the systemic extent of disease.

Instead of isolated recurrence, the patient demonstrates disseminated metastatic involvement.

This distinction fundamentally changes therapeutic strategy, shifting management from localized treatment toward systemic therapy.


Diagnostic Imaging Pearls

✔ Always assess whether disease is localized or systemic.

✔ MIP images provide the fastest overview of metastatic burden.

✔ High FDHT uptake indicates preserved androgen receptor expression.

✔ Diffuse skeletal involvement may occur despite a negative bone scan.


Figure 4. Axial PET/CT Fusion Images

Axial fusion images demonstrate increased FDHT uptake within metastatic lymph nodes and skeletal lesions while simultaneously providing precise anatomical localization.


Radiologist Interpretation

Technique

Hybrid PET/CT fusion imaging

Findings

The fused examination demonstrates:

  • Hypermetabolic lymph node lesions
  • Skeletal metastatic foci
  • Accurate anatomical localization through CT correlation

Fusion imaging combines functional molecular information with structural anatomy, improving confidence in lesion localization and staging.


Why Fusion Imaging Matters

PET alone depicts tracer uptake.

CT alone depicts anatomy.

PET/CT fusion integrates both datasets, allowing radiologists to determine precisely where biologically active disease is located.

The uploaded case emphasizes this advantage when discussing lymph node assessment and treatment planning.


Figure 5. Skeletal Metastatic Disease

Axial fusion images demonstrate abnormal FDHT uptake involving the sternum, ribs, scapulae, vertebral column, and pelvic bones, consistent with extensive skeletal metastatic disease.


Radiologist Interpretation

Distribution

Metastatic lesions involve:

  • Sternum
  • Ribs
  • Scapulae
  • Vertebral column
  • Pelvis

These findings indicate widespread osseous metastatic disease with preserved androgen receptor expression.


Sample Radiology Report

Findings

Whole-body 18F-FDHT PET/CT demonstrates multiple areas of increased radiotracer uptake involving supradiaphragmatic and infradiaphragmatic lymph nodes as well as extensive skeletal lesions involving the sternum, ribs, scapulae, vertebral column, and pelvis. All visualized lesions demonstrate increased androgen receptor tracer uptake.

Impression

  1. Extensive metastatic prostate carcinoma involving lymph nodes and axial skeleton.
  2. Diffuse androgen receptor-positive metastatic disease.
  3. Findings support systemic metastatic progression despite previously negative bone scintigraphy.
  4. Imaging findings are suitable for consideration of androgen receptor-targeted systemic therapy, consistent with the management described in the case.

Clinical Correlation

One of the most clinically significant aspects of this case is the discrepancy between conventional and molecular imaging.

The uploaded case documents the following sequence:

  1. Ongoing LHRH agonist therapy
  2. Normal bone scintigraphy
  3. FDHT PET/CT reveals extensive nodal and skeletal metastases
  4. High androgen receptor expression across all lesions
  5. Referral for androgen receptor antagonist therapy

This progression illustrates that the purpose of re-staging extends beyond detecting disease—it directly informs the next therapeutic decision.


Multimodal Imaging Comparison

Imaging ModalityStrengthsLimitationsClinical Value
Bone ScanDetects osteoblastic responseMay miss early metastatic diseaseConventional skeletal survey
CTExcellent anatomical detailLimited functional informationNodal and structural assessment
18F-FDHT PET/CTDirect visualization of androgen receptor expressionAvailability and specialized indicationFunctional re-staging and therapy planning
PET/CT FusionCombines molecular and anatomical informationHigher complexityImproved lesion localization

This comparison reflects the educational emphasis of the uploaded case regarding why FDHT PET/CT altered staging after a negative bone scan.

7. Differential Diagnosis

Why Differential Diagnosis Matters During Re-staging

One of the greatest challenges in oncologic imaging is distinguishing true metastatic disease from benign or treatment-related abnormalities. Although molecular imaging substantially improves lesion detection, interpretation must always be integrated with the patient's clinical history, laboratory findings, and prior imaging.

The uploaded case specifically notes that its differential diagnosis section represents general clinical concepts rather than findings directly observed in this patient. The following considerations therefore combine the source material with standard radiologic reasoning, clearly distinguishing the educational framework from the confirmed case findings.


Table 2. Imaging Differential Diagnosis During Prostate Cancer Re-staging

DiseaseCT FindingsPET/MRI FindingsPathologyKey Differentiating Feature
Metastatic prostate cancerEnlarged lymph nodes, osseous lesionsHigh AR tracer uptakeAdenocarcinomaMultifocal AR-positive disease
Post-treatment changeFibrosis or sclerosisVariable uptakeFibrotic tissueStable over time
Degenerative bone diseaseOsteophytes, sclerosisMinimal or absent tracer uptakeBenign degenerationTypical degenerative distribution
Reactive lymphadenopathyMild nodal enlargementLow-level uptakeReactive hyperplasiaClinical inflammatory context
Other metastatic malignanciesVariableDepends on tumor biologyVariableDifferent molecular imaging profile

Differential Diagnosis in the Present Case

The uploaded case documents widespread FDHT uptake involving:

  • Supradiaphragmatic lymph nodes
  • Infradiaphragmatic lymph nodes
  • Sternum
  • Ribs
  • Scapulae
  • Vertebral column
  • Pelvis

Combined with uniformly high androgen receptor expression, strongly supports metastatic prostate carcinoma rather than benign disease.


Imaging Pitfalls

Experienced radiologists routinely consider several potential pitfalls:

Pitfall 1

Assuming a normal bone scan excludes metastatic disease.

This case clearly demonstrates that such an assumption may be incorrect.


Pitfall 2

Interpreting molecular imaging without considering tumor biology.

FDHT PET visualizes androgen receptor expression—not simply tumor size.


Pitfall 3

Ignoring biochemical recurrence.

Persistently rising PSA may indicate progressive disease even when structural imaging appears normal.


Imaging Pearls

✓ Always correlate PET findings with PSA kinetics.

✓ Review prior imaging before assigning progression.

✓ Evaluate the distribution pattern rather than isolated lesions.

✓ Molecular imaging complements—not replaces—clinical judgment.


8. Treatment Strategy

The Ultimate Goal of Re-staging

The uploaded case repeatedly emphasizes that re-staging is not merely an exercise in lesion detection. Its primary objective is to guide the next phase of treatment.

In this patient, the imaging findings directly altered therapeutic planning.


Conservative Management

For localized recurrence without distant metastasis, treatment options may include:

  • Active surveillance in selected patients
  • PSA monitoring
  • Imaging follow-up

The present case, however, demonstrated disseminated disease and therefore required systemic evaluation.


Medical Therapy

According to the uploaded case:

  • The patient had already received LHRH agonist therapy.
  • FDHT PET/CT subsequently demonstrated widespread AR-positive metastases.
  • Referral for androgen receptor antagonist therapy followed.

This sequence highlights how molecular imaging can influence treatment selection.


Surgical Treatment

The source document does not describe surgical management after re-staging.

Therefore, no surgery-specific conclusions can be drawn from this case.


Radiation Therapy

The uploaded case does not include radiation treatment.

Its therapeutic focus remains systemic management following molecular re-staging.


Emerging Systemic Therapies

Beyond the scope of the uploaded case, contemporary management of advanced prostate cancer may include:

  • Second-generation androgen receptor inhibitors
  • Chemotherapy
  • Radioligand therapy
  • Combination systemic therapy

These options should be individualized according to international clinical guidelines and multidisciplinary evaluation.


AI-Assisted Treatment Planning

Artificial intelligence is expected to contribute to treatment selection by integrating:

  • Molecular imaging
  • PSA kinetics
  • Genomic profiling
  • Clinical staging
  • Prior treatment history
  • Longitudinal imaging

Instead of relying upon a single examination, AI systems may generate individualized risk predictions throughout the patient's clinical journey.


9. Prognosis

Prognostic Information Available from the Case

The uploaded document explicitly states that long-term follow-up information is not available.

Accordingly, the following outcomes cannot be determined from the case itself:

  • Progression-free survival
  • Overall survival
  • Treatment response
  • Long-term recurrence rate

The principal confirmed conclusion is that imaging findings resulted in modification of therapeutic planning.


Prognostic Factors Identified

Several adverse features documented in the uploaded case suggest biologically aggressive disease:

  • Age: 86 years
  • Clinical stage cT4
  • Gleason score 10
  • PSA 120 ng/mL
  • Multiple skeletal metastases
  • Extensive nodal metastases

These factors characterize a very high-risk clinical profile.


10. Artificial Intelligence Perspective

Why This Case Matters for Medical AI

Most current AI algorithms detect anatomical abnormalities.

This case illustrates a different challenge:

How can AI interpret tumor biology rather than morphology alone?

18F-FDHT PET/CT provides functional information regarding androgen receptor activity.

Future AI systems will increasingly integrate such molecular biomarkers into clinical decision support.


Radiomics

Radiomics extracts hundreds to thousands of quantitative imaging features beyond what human visual perception can detect.

Potential FDHT PET radiomic biomarkers include:

  • Uptake heterogeneity
  • Spatial distribution
  • Texture entropy
  • Shape complexity
  • Lesion clustering
  • Total receptor-positive tumor burden

These features may improve:

  • Response prediction
  • Risk stratification
  • Survival modeling
  • Therapy selection

Foundation Models

Large medical imaging foundation models can potentially learn relationships among:

  • PET
  • CT
  • MRI
  • Histopathology
  • Laboratory data
  • Genomics

Rather than recognizing isolated lesions, these models may develop a comprehensive representation of the biology of metastatic prostate cancer.


Vision-Language Models (VLMs)

Future radiology workflows may employ multimodal AI capable of integrating:

  • PET images
  • CT anatomy
  • Radiology reports
  • PSA values
  • Clinical history
  • Pathology reports

The output could include automatically generated structured reports, differential diagnoses, and treatment recommendations for clinician review.


Clinical Decision Support

AI-driven decision support systems may assist clinicians by:

  • Identifying occult metastatic disease
  • Comparing serial PET examinations
  • Quantifying whole-body tumor burden
  • Estimating progression risk
  • Suggesting guideline-concordant treatment pathways

Importantly, such systems are designed to support—not replace—physician judgment.


Enterprise AI Workflow

Figure 6. Enterprise Molecular Imaging AI Workflow

Enterprise workflow illustrating integration of molecular imaging into a hospital AI ecosystem, from image acquisition to clinical decision support.


Enterprise Architecture

Modern molecular imaging increasingly depends on seamless interoperability among hospital information systems.

Key components include:

  • PET/CT scanners
  • PACS
  • Vendor-neutral archives (VNA)
  • AI orchestration platforms
  • DICOM standards
  • HL7 messaging
  • FHIR-based interoperability
  • Electronic health records
  • Oncology information systems

Such integration enables AI to deliver clinically actionable insights without disrupting established radiology workflows.


Limitations of Artificial Intelligence

Despite rapid advances, AI has important limitations.

AI may:

  • Miss uncommon metastatic patterns
  • Misinterpret imaging artifacts
  • Perform inconsistently across institutions
  • Be affected by scanner variability
  • Depend on high-quality annotations
  • Require continuous external validation

Consequently, expert radiologist oversight remains essential, particularly when interpreting advanced molecular imaging such as 18F-FDHT PET/CT.

11. Future of Precision Medicine

Beyond Anatomical Imaging

The history of prostate cancer imaging has evolved from anatomical visualization to functional imaging and, increasingly, to molecular characterization.

This case illustrates that transition clearly.

Rather than merely identifying enlarged lymph nodes or sclerotic bone lesions, 18F-FDHT PET/CT evaluates androgen receptor (AR) expression, providing biological information that can influence therapeutic decisions. In this patient, widespread AR-positive disease identified on PET/CT supported referral for AR antagonist therapy.


Radiogenomics

Educational Perspective (Beyond the Source File)

Radiogenomics seeks to correlate imaging phenotypes with genomic alterations.

Potential future applications include:

  • Predicting androgen receptor pathway activation
  • Estimating treatment resistance
  • Identifying aggressive molecular subtypes
  • Forecasting therapeutic response

Although the uploaded case documents high AR expression on FDHT PET/CT, it does not include genomic testing or radiogenomic analysis.


Digital Twin Technology

A digital twin is a computational representation of an individual patient that continuously integrates:

  • Imaging
  • Laboratory results
  • Histopathology
  • Genomics
  • Treatment history
  • Clinical outcomes

Future oncology platforms may simulate treatment responses before therapy begins.

This technology is not described in the uploaded case, but represents an emerging direction in precision oncology.


Federated Learning

Medical imaging AI often encounters privacy restrictions.

Federated learning enables multiple hospitals to train shared AI models without exchanging patient data directly.

Potential advantages include:

  • Better generalization
  • Increased dataset diversity
  • Improved regulatory compliance
  • Reduced privacy risks

Synthetic Data

Rare imaging biomarkers, including AR-targeted PET tracers such as FDHT, often suffer from limited training datasets.

Synthetic data generation may eventually help AI developers:

  • Improve model robustness
  • Reduce class imbalance
  • Enhance validation of rare imaging findings

Again, this concept extends beyond the uploaded case.


Multimodal Precision Imaging

Future diagnostic systems are expected to combine:

  • PET
  • CT
  • MRI
  • Histopathology
  • Genomics
  • Blood biomarkers
  • Clinical records

Rather than interpreting each modality independently, integrated AI systems may generate comprehensive patient-specific assessments.


12. Clinical Pearls

The uploaded case emphasizes several practical lessons for radiologists and oncologists.

Clinical Pearl 1

A normal bone scan does not exclude metastatic prostate cancer.


Clinical Pearl 2

Persistent PSA elevation should prompt reassessment even when conventional imaging is negative.


Clinical Pearl 3

Re-staging aims to guide treatment decisions, not merely detect lesions.


Clinical Pearl 4

18F-FDHT PET/CT visualizes androgen receptor biology rather than osteoblastic activity.


Clinical Pearl 5

Molecular imaging can reveal metastatic disease before structural skeletal changes become apparent.


Clinical Pearl 6

Whole-body MIP images rapidly demonstrate systemic disease distribution.


Clinical Pearl 7

PET/CT fusion improves anatomical localization of biologically active lesions.


Clinical Pearl 8

Uniformly increased FDHT uptake suggests preserved androgen receptor expression.


Clinical Pearl 9

High-risk clinical features—including Gleason score 10 and PSA 120 ng/mL—should always be interpreted together with imaging findings.


Clinical Pearl 10

Clinical management should integrate imaging, laboratory data, and multidisciplinary expertise rather than rely on a single modality.


Clinical Pearl 11

Functional imaging often provides information that conventional anatomical imaging cannot.


Clinical Pearl 12

Radiologists should evaluate disease distribution before focusing on individual lesions.


Clinical Pearl 13

Molecular imaging increasingly supports personalized oncology.


Clinical Pearl 14

Artificial intelligence may assist interpretation, but final responsibility remains with experienced physicians.


Clinical Pearl 15

The greatest value of advanced imaging lies in changing patient management—not simply producing better pictures.


Quiz

Question 1

In the uploaded case, what prompted molecular re-staging?

① Acute urinary retention

② Elevated serum creatinine

③ Rising PSA during LHRH agonist therapy

④ Gross hematuria

⑤ Fever

Correct Answer:

Explanation: The patient underwent re-staging because PSA increased despite ongoing hormonal therapy.


Question 2

Which imaging finding most directly influenced the treatment strategy?

① Negative bone scan

② Enlarged prostate gland

③ Extensive AR-positive lymph node and skeletal metastases on FDHT PET/CT

④ Benign lymph node enlargement

⑤ Bladder wall thickening

Correct Answer:

Explanation: FDHT PET/CT demonstrated widespread metastatic disease with high androgen receptor expression, leading to referral for AR antagonist therapy.


Question 3

According to the uploaded case, what does 18F-FDHT primarily visualize?

① Bone remodeling

② Calcium metabolism

③ Glucose metabolism

④ Androgen receptor expression

⑤ DNA synthesis

Correct Answer:

Explanation: FDHT binds to androgen receptors, allowing visualization of receptor expression rather than osteoblastic activity.


Question 4

Which statement best summarizes the educational message of the case?

① Bone scintigraphy is always sufficient.

② PET/CT should replace every imaging examination.

③ Molecular imaging may alter staging and treatment when conventional imaging is inconclusive.

④ PSA has little clinical value.

⑤ Lymph node metastases are clinically unimportant.

Correct Answer:

Explanation: The uploaded case demonstrates how FDHT PET/CT changed staging and subsequent treatment planning despite a negative bone scan.


Question 5

The uploaded case specifically states that long-term survival outcomes:

① Were excellent

② Demonstrated complete remission

③ Were unavailable

④ Showed rapid recurrence

⑤ Confirmed cure

Correct Answer:

Explanation: The case does not provide long-term follow-up or survival data.


14. Frequently Asked Questions (FAQ)

Q1. Does a normal bone scan rule out metastatic prostate cancer?

No. The uploaded case demonstrates that extensive metastatic disease was identified on 18F-FDHT PET/CT despite a normal bone scan.


Q2. Why was FDHT PET/CT performed?

To re-stage disease after PSA elevation during treatment and to guide further therapy.


Q3. What biological target does FDHT image?

The uploaded case explains that FDHT binds to androgen receptors and visualizes AR expression.


Q4. Which metastatic sites were identified?

The case reports metastases involving lymph nodes above and below the diaphragm and multiple skeletal sites including the sternum, ribs, scapulae, vertebral column, and pelvis.


Q5. Did PET/CT change treatment?

Yes. According to the case, the patient was referred for androgen receptor antagonist therapy after PET/CT findings.


Q6. Did the uploaded case include genomic testing?

No. Genomic analysis is not described in the source document.


Q7. Were MRI findings provided?

No. The uploaded case focuses on FDHT PET/CT rather than MRI.


Q8. Does the case include survival data?

No. Long-term follow-up is explicitly stated to be unavailable.


Q9. Can AI replace radiologists in interpreting molecular imaging?

The uploaded case does not address this question. Educationally, AI should be viewed as a clinical support tool rather than a replacement for expert interpretation.


Q10. What is the single most important lesson from this case?

The educational point highlighted in the uploaded case is that 18F-FDHT PET/CT plays an important role in re-staging advanced prostate cancer and in guiding subsequent treatment decisions.


Conclusion

This case demonstrates how molecular imaging can fundamentally alter clinical decision-making in advanced prostate cancer.

The uploaded case documents an 86-year-old man with high-risk prostate cancer whose bone scan was negative, yet 18F-FDHT PET/CT revealed extensive androgen receptor-positive lymph node and skeletal metastases, leading to referral for androgen receptor antagonist therapy.

The central lesson is not that FDHT PET/CT should replace all conventional imaging, but that its ability to visualize androgen receptor biology can uncover clinically significant disease that conventional bone scintigraphy may not detect in selected patients. Within the limits of the case, molecular imaging provided information that directly influenced re-staging and treatment planning.

As precision oncology advances, future integration of molecular imaging, quantitative image analysis, and AI-assisted clinical decision support has the potential to further personalize prostate cancer care. Those future directions, however, extend beyond the evidence presented in this individual case and will require validation through prospective clinical studies.

References

  1. J. S. Dehdashti et al., "Assessment of androgen receptor expression with 18F-FDHT PET in metastatic prostate cancer," J. Nucl. Med., 2011. DOI: 10.2967/jnumed.111.089714.
  2. M. E. Pienta et al., "PET Imaging in Prostate Cancer," Radiology, 2020. DOI: 10.1148/radiol.2020191435.
  3. H. Jadvar, "Molecular Imaging of Prostate Cancer," J. Nucl. Med., 2013. DOI: 10.2967/jnumed.112.109298.
  4. C. N. Sternberg et al., "ESMO Clinical Practice Guidelines: Prostate Cancer."
  5. P. Cornford et al., "EAU Guidelines on Prostate Cancer."
  6. J. Mohler et al., "NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer."
  7. M. Hofman et al., "Prostate-specific membrane antigen PET," Lancet Oncology, 2020.
  8. A. Afshar-Oromieh et al., "Diagnostic Value of PET Imaging in Prostate Cancer."
  9. R. J. Gillies, P. Kinahan, and H. Hricak, "Radiomics: Images Are More than Pictures," Radiology, 2016.

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