Bone marrow biopsy: RNA isolation with expression profiling in men with metastatic castration-resistant prostate cancer--factors affecting diagnostic success

Abstract

Purpose: To determine the rate at which computed tomographically guided pelvic percutaneous bone biopsy in men with metastatic castration-resistant prostate cancer (mCRPC) yields adequate tissue for genomic profiling and to identify issues likely to affect diagnostic yields.

Materials and methods: This study was institutional review board approved, and written informed consent was obtained. In a phase II trial assessing response to everolimus, 31 men with mCRPC underwent 54 biopsy procedures (eight men before and 23 men both before and during treatment). Variables assessed were lesion location (iliac wing adjacent to sacroiliac joint, iliac wing anterior and/or superior to sacroiliac joint, sacrum, and remainder of pelvis), mean lesion attenuation, subjective lesion attenuation (purely sclerotic vs mixed), central versus peripheral lesion sampling, lesion size, core number, and use of zoledronic acid for more than 1 year.

Results: Of 54 biopsy procedures, 21 (39%) yielded adequate tissue for RNA isolation and genomic profiling. Three of four sacral biopsies were adequate. Biopsies of the ilium adjacent to the sacroiliac joints were more likely adequate than those from elsewhere in the ilium (48% vs 28%, respectively). All five biopsies performed in other pelvic locations yielded inadequate tissue for RNA isolation. Mean attenuation of lesions with inadequate tissue was 172 HU greater than those with adequate tissue (621.1 HU ± 166 vs 449 HU ± 221, respectively; P = .002). Use of zoledronic acid, peripheral sampling, core number, and lesion size affected yields, but the differences were not statistically significant. Histologic examination with hematoxylin-eosin staining showed that results of 36 (67%) biopsies were positive for cancer; only mean attenuation differences were significant (707 HU ± 144 vs 473 HU ± 191, negative vs positive, respectively; P < .001).

Conclusion: In men with mCRPC, percutaneous sampling of osseous metastases for genomic profiling is possible, but use of zoledronic acid for more than 1 year may reduce the yield of adequate tissue for RNA isolation. Sampling large low-attenuating lesions at their periphery maximizes yield.

Figure 1a:

(a) CT and (b) CT fluoroscopic images of a mixed lesion sampled centrally. The biopsy result was adequate for RNA isolation.

Figure 1b:

(a) CT and (b) CT fluoroscopic images of a mixed lesion sampled centrally. The biopsy result was adequate for RNA isolation.

Figure 2a:

(a) CT and (b) CT fluoroscopic images of a sclerotic lesion sampled peripherally. The biopsy was adequate for RNA isolation.

Figure 2b:

(a) CT and (b) CT fluoroscopic images of a sclerotic lesion sampled peripherally. The biopsy was adequate for RNA isolation.

Figure 3:

Box-and-whisker plot shows mean attenuation values and biopsy results. Differences in attenuation between positive and negative biopsy groups were significant, (histologic evaluation with H-E, P < .001; RNA isolation, P = .002; bootstrap difference of means). For RNA isolation, positive indicates adequate tissue and negative indicates inadequate tissue for isolation.