Initial experience of Ga-68 prostate-specific membrane antigen positron emission tomography/computed tomography imaging in evaluation of biochemical recurrence in prostate cancer patients

Aravintho Natarajan, Archi Agrawal, Vedang Murthy, Ganesh Bakshi, Amit Joshi, Nilendu Purandare, Sneha Shah, Ameya Puranik, Venkatesh Rangarajan, Aravintho Natarajan, Archi Agrawal, Vedang Murthy, Ganesh Bakshi, Amit Joshi, Nilendu Purandare, Sneha Shah, Ameya Puranik, Venkatesh Rangarajan

Abstract

Gallium-68 labeled prostate-specific membrane antigen (Ga-68 PSMA) ligand (HBED-CC) is a novel tracer used for prostate cancer imaging. The aim of the study was to investigate the performance of Ga-68 PSMA positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) after definitive treatment. Scans of 96 consecutive patients were analyzed. Sixty-two patients received external beam radiotherapy, 34 underwent radical prostatectomy (RP), and 20 patients were on androgen deprivation therapy. Patients with prostate-specific antigen (PSA) level ≥>0.2 ng/mL following RP and PSA rise by 2 ng/mL or more above the nadir PSA following RT (Phoenix criteria) was considered as BCR, respectively. All patients underwent contrast-enhanced PET/CT after injection of 67-111 MBq Ga-68 PSMA ligand. Detection rates were correlated with serum PSA level. Detection rate for nodal metastases was compared with CT. Results of the scan were validated by using either biopsy or follow-up imaging or clinical follow-up. Seventy-four (77%) patients showed abnormal finding in Ga-68 PSMA PET/CT. The median serum PSA level of the population was 5.5 ng/ml (range 0.2-123 ng/ml). The median PSA of the positive scans was higher than that of the negative scans (6 vs. 1.7 ng/ml) and was statistically significant (P = 0.001 by Mann-Whitney U-test). In post-RP group, the detection rates were 23%, 50%, and 82% for PSA <1, 1-2, and >2 ng/ml, respectively. For post-RT, the detection was 86%, 85%, and 95% for PSA 2-5, 5.1-10, and >10 ng/ml, respectively. PSMA PET/CT revealed nodal metastases in 52 (54%) patients while CT showed pathological nodes only in 27 (28%) patients. Overall PSMA PET/CT revealed more number of nodes than CT (111 vs. 48 nodal station). PSMA PET/CT showed relapse in prostate/prostatic bed in 26 (27%) patients, nodal metastases in 50 (52%), skeletal metastases in 20 (21%), and other sites in 4 (4%) patients. Ga-68 PSMA PET/CT has high detection rate for localizing the site of recurrence in patients with biochemical failure and is superior to CT scan in the detection of nodal disease.

Keywords: Biochemical failure; Gallium-68 Prostate-specific membrane antigen; biochemical recurrence; positron emission tomography; prostate cancer.

Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Recurrence in prostate: Patient presented with serum prostate-specific antigen of 3 ng/ml following radical external beam radiotherapy. Maximum intensity projection image (a) shows intense focal tracer uptake in the region of prostate (arrow). Axial view of CT (b) and Fused (c) images confirms confirms the focal uptake in the prostate. Subsequently, the patient responded to salvage Brachytherapy and the serum prostate-specific antigen fell to 0.86 ng/ml
Figure 2
Figure 2
Nodal recurrence: Postexternal beam radiotherapy, the patient presented with serum prostate-specific antigen of 4 ng/ml. Whole body maximum intensity projection (a) image shows multiple focal tracer uptake in mediastinum, abdomen, and pelvis. Axial fusion images (c and e) show intense uptake in subcentimeter-sized retroperitoneal (block arrow) and mediastinal nodes (arrow), respectively. The size of all these nodes was not abnormal in CT (b and d). Patients were subsequently started on androgen deprivation therapy but progressed to castrate resistant disease
Figure 3
Figure 3
Skeletal metastases: Postexternal beam radiotherapy and adjuvant androgen deprivation therapy presented with prostate-specific antigen of 5.5 ng/ml. Maximum intensity projection images (a) show focal increased uptake in thorax, abdomen, and pelvis. The fused axial images reveal uptake in thoracic vertebrae (arrow) (b) and subcentimeter-sized retroperitoneal nodes (c). (Note: Increased tracer uptake noted in liver (block arrow) actually corresponds to gall bladder (d and e), and is not pathological but a physiological variant)
Figure 4
Figure 4
Visceral metastases: Following external beam radiotherapy, patient presented with scrotal swelling and rising prostate-specific antigen of 11.2 ng/ml. Maximum intensity projection (a) image show focal tracer uptake in liver (block arrow) and in scrotum (line arrow). Axial computed tomography (b) and fused images (c) show increased tracer uptake noted in the left testicular swelling. Images (d and e) show focal uptake in enhancing lesion in right lobe of liver. Subsequently, bilateral orchidectomy was done and the histopathology report confirmed metastatic adenocarcinoma and were positive for prostate-specific antigen in immunohistochemistry
Figure 5
Figure 5
Histogram chart of number of patients with disease recurrence at various sites
Figure 6
Figure 6
Comparison of detection rate of prostate-specific membrane antigen positron emission tomography/computed tomography and contrast-enhanced computed tomography for nodal metastases
Figure 7
Figure 7
Postradical prostatectomy patient presented with prostate-specific antigen of 3 ng/ml. Whole body maximum intensity projection image (a) and fusion image (b) reveal intense uptake in subcentimeter-sized bilateral pelvic nodes (arrows). Following 6 months of androgen deprivation therapy, prostate-specific antigen decreased to 0.09 and follow-up prostate-specific membrane antigen positron emission tomography images (c and d) revealed complete resolution of prostate-specific membrane antigen expression in the pelvic nodes
Figure 8
Figure 8
Frequency histogram of detection rate of prostate-specific membrane antigen positron emission tomography at various prostate-specific antigen level in postradical prostatectomy group
Figure 9
Figure 9
Frequency histogram of detection rate of prostate-specific membrane antigen positron emission tomography at various prostate-specific antigen level in postradical prostatectomy group

References

    1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.
    1. Jain S, Saxena S, Kumar A. Epidemiology of prostate cancer in India. Meta Gene. 2014;2:596–605.
    1. Bruce JY, Lang JM, McNeel DG, Liu G. Current controversies in the management of biochemical failure in prostate cancer. Clin Adv Hematol Oncol. 2012;10:716–22.
    1. Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: Treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol. 2017;71:630–42.
    1. Cher ML, Bianco FJ, Jr, Lam JS, Davis LP, Grignon DJ, Sakr WA, et al. Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy. J Urol. 1998;160:1387–91.
    1. Beer AJ, Eiber M, Souvatzoglou M, Schwaiger M, Krause BJ. Radionuclide and hybrid imaging of recurrent prostate cancer. Lancet Oncol. 2011;12:181–91.
    1. Castellucci P, Ceci F, Graziani T, Schiavina R, Brunocilla E, Mazzarotto R, et al. Early biochemical relapse after radical prostatectomy: Which prostate cancer patients may benefit from a restaging 11C-choline PET/CT scan before salvage radiation therapy? J Nucl Med. 2014;55:1424–9.
    1. Bařinka C, Rojas C, Slusher B, Pomper M. Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer. Curr Med Chem. 2012;19:856–70.
    1. Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52:637–40.
    1. Trock BJ, Han M, Freedland SJ, Humphreys EB, DeWeese TL, Partin AW, et al. Prostate cancer-specific survival following salvage radiotherapy vs. observation in men with biochemical recurrence after radical prostatectomy. JAMA. 2008;299:2760–9.
    1. Amling CL, Lerner SE, Martin SK, Slezak JM, Blute ML, Zincke H. Deoxyribonucleic acid ploidy and serum prostate specific antigen predict outcome following salvage prostatectomy for radiation refractory prostate cancer. J Urol. 1999;161:857–62.
    1. Kane CJ, Amling CL, Johnstone PA, Pak N, Lance RS, Thrasher JB, et al. Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy. Urology. 2003;61:607–11.
    1. Hövels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: A meta-analysis. Clin Radiol. 2008;63:387–95.
    1. Fitzpatrick C, Lynch O, Marignol L. 68Ga-PSMA-PET/CT has a role in detecting prostate cancer lesions in patients with recurrent disease. Anticancer Res. 2017;37:2753–60.
    1. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56:668–74.
    1. Lengana T, van de Wiele C, Lawal I, Maes A, Ebenhan T, Boshomane T, et al. 68Ga-PSMA-HBED-CC PET/CT imaging in black versus white South African patients with prostate carcinoma presenting with a low volume, androgen-dependent biochemical recurrence: A prospective study. Nucl Med Commun. 2018;39:179–85.
    1. Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med. 2015;56:1185–90.
    1. Einspieler I, Rauscher I, Düwel C, Krönke M, Rischpler C, Habl G, et al. Detection efficacy of hybrid 68Ga-PSMA ligand PET/CT in prostate cancer patients with biochemical recurrence after primary radiation therapy defined by phoenix criteria. J Nucl Med. 2017;58:1081–7.
    1. Cooperberg MR, Hilton JF, Carroll PR. The CAPRA-S score: A straightforward tool for improved prediction of outcomes after radical prostatectomy. Cancer. 2011;117:5039–46.
    1. Ferdinandus J, Violet J, Sandhu S, Hofman MS. Prostate-specific membrane antigen theranostics: Therapy with lutetium-177. Curr Opin Urol. 2018;28:197–204.

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