Hematology/Oncology

One of the cornerstones of appropriate cancer treatment is staging.

As newer imaging modalities become available, and as data on a technology’s utility is compiled, ideal treatment options can be more closely refined to a patient’s case.

In the current case, a relatively new radiologic technique led to the patient being diagnosed with a more advanced cancer stage, but it simultaneously increased his treatment options.

The patient is an 80-year-old male with a history of prostate cancer dating back 14 years.

At diagnosis, he had a PSA value of 13.6 ng/mL and was found to have a Gleason score of 3 + 4 adenocarcinoma of the prostate. He underwent definitive local therapy with external beam radiation. The patient had an excellent response, with a PSA decrease to undetectable levels for the next 6 years.

The patient then experienced a biochemical recurrence, with a PSA rise to 5.4 ng/mL.

Leuprolide was initiated, and the PSA decreased to 0.2 ng/mL within 5 months. However, 6 months later, the PSA rose again, this time to 1.1 ng/mL.

He was consequently assigned bicalutamide besides leuprolide. He again had a biochemical response, but the PSA fluctuated during the next 5 years between 0.6 ng/mL and 1.2 ng/mL. No evidence of metastatic disease was identified on imaging.

In December 2010, the PSA rose incrementally to 2.3 ng/mL. At that time, the patient had been asymptomatic, with no pain or urinary symptoms.

Four months later, the PSA rose further to 4.9 ng/mL. Due to this increasing value, a strategy of antiandrogen withdrawal was employed, with discontinuation of bicalutamide. The PSA decreased slightly to 4.52 ng/mL, but 1 month later, it jumped to 5.84 ng/mL.

Temporally coinciding with the discontinuation of bicalutamide, the patient began to experience increasing pain in the low back, right hip and right leg. Whereas he previously was able to walk with a cane, he now required a walker.

In addition, he started to consume narcotic analgesics at an increasing frequency during the following 2 months. During this time, his PSA rose to 6.88 ng/mL after 1 month and then 8.84 ng/mL in the second month. In concert with his pain symptomatology, a bone scan was repeated and again was negative. Serum testosterone remained suppressed during this entire period at less than 25 ng/dL.

Despite the negative imaging studies, the patient clinically was worsening, and with the concomitant rise in the PSA value, it was difficult to attribute his progressive symptoms to osteoarthritis alone.

The dilemma was that metastatic bony disease was strongly suspected, but it would not be standard practice to offer a treatment option for metastatic prostate cancer without more concrete evidence. This ideally would be either in the form of imaging or a pathologic specimen.

Given this situation, an 18F-labeled sodium-fluoride PET scan was pursued. This relatively newer modality was specifically utilized to assess bony metastatic disease with greater sensitivity and specificity compared with a bone scan. This imaging confirmed what was suspected clinically: significant uptake on the PET scan was seen at L2-L4 (Figure 1).

This result provided evidence fitting with the clinical picture. As such, the patient has been offered multiple possible first-line metastatic castrate-refractory prostate cancer therapeutic approaches, including immunotherapy with sipuleucel-T (Provenge, Dendreon), clinical trials and chemotherapy. Adjunctive bone-stabilizing therapies also have been discussed. Hopefully, one of the anti-neoplastic treatments, by more effectively targeting prostate carcinoma, will also afford symptom relief for the patient.

Discussion

In this case, the physicians believed there was a high pretest probability for metastatic prostate adenocarcinoma. Unfortunately, standard imaging studies were unable to confirm this. Because it is a sizable step prognostically and therapeutically to deem a patient’s malignancy as metastatic, more conclusive evidence was sought, and ideally with findings that properly conform to the clinical scenario.

Interestingly, sodium-fluoride PET scanning is a technique dating to the 1960s, when the first probes were developed. It was studied and utilized briefly for skeletal scintigraphy, before the widespread adoption of 99mTc-labeled bone imaging.

The landscape for this technology has changed as PET scanning machinery is more widely available, prompting ongoing research in this radiological arena.

Although 18F-labeled sodium-fluoride PET scans are only obtainable in a limited distribution currently, there is a growing body of literature supporting its utility.

The 18F-labeled probe has a very bone-specific deposition. Studies have shown that 90% to 98% of the tracer is delivered to bone after a single pass of blood. Aided by a high “bone-to-background” ratio, this is an imaging modality that allows quantitative bone imaging for metastatic disease. Negligible uptake is seen in the bone marrow. Importantly, at least with contemporary techniques, the pattern of uptake is more important than simply the degree of uptake.

Comparisons with 99mTc-labeled bone scans are seemingly favorable. Sensitivity is reported as 91%, and specificity is reported as 83%. Additionally, imaging quality may be superior with 18F-labeled sodium-fluoride PET scans.

With multiple new therapies approved in the past few years — including immunotherapy with sipuleucel-T, chemotherapy with cabazitaxel (Jevtana, Sanofi-Aventis), and abiraterone (Zytiga, Janssen Biotech) — it is an exciting time in prostate carcinoma. Several very promising clinical trials also are in process, particularly targeting androgen receptor signaling from different angles. With these advances, it is critical that the art and science of patient selection is performed meticulously to optimize and coordinate these treatments in the best manner for an individual patient.

Amit Mehta, MD, is an attending physician at Regional Cancer Care in Durham, N.C., and is a member of the HemOnc Today Editorial Board. Disclosure: Dr. Mehta reports no relevant financial disclosures.

For more information:

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