Abstract
A 78-year-old man presented with a prostate-specific antigen (PSA) level of 35 ng/mL, a PI-RADS 5 lesion on multiparametric prostate MRI, and negative whole-body bone scintigraphy. Within five months, PSA increased to 1244 ng/mL despite minimal radiological progression of the primary tumour. Repeat MRI demonstrated multiple osseous lesions, repeat MRI–ultrasound fusion-guided biopsy confirmed Grade Group 5 adenocarcinoma with cribriform architecture and perineural invasion, and repeat bone scintigraphy revealed an oncologic superscan consistent with high-volume metastatic disease. This case demonstrates that rapidly rising PSA levels accompanied by new skeletal symptoms should prompt immediate repeat staging despite initially negative whole-body bone scintigraphy.
Keywords: Prostate cancer, Bone scintigraphy, Superscan, Prostate-specific antigen, Skeletal metastases, Grade group 5
1. Introduction
Prostate cancer usually follows a relatively predictable clinical course, with local tumour progression preceding metastatic dissemination. However, a subset of tumours demonstrates highly aggressive biological behaviour characterized by rapid prostate-specific antigen (PSA) escalation and early metastatic dissemination. The superscan pattern on bone scintigraphy reflects diffuse skeletal involvement with markedly increased osteoblastic activity and is typically associated with extensive metastatic burden and advanced disease.1
We report an unusual case of Grade Group 5 prostate adenocarcinoma demonstrating progression from negative whole-body bone scintigraphy to an oncologic superscan within five months despite minimal radiological progression of the primary prostate lesion. This case highlights the limitations of conventional skeletal staging in rapidly evolving disease and emphasizes the importance of prompt repeat imaging in patients presenting with rapidly increasing PSA levels and new skeletal symptoms.
2. Case presentation
A 78-year-old man was referred to our institution in December 2024 because of an abnormal digital rectal examination and elevated prostate-specific antigen (PSA). The referral PSA level was approximately 25.3 ng/mL and increased to 35 ng/mL on 2 December 2024. Multiparametric prostate MRI performed on 9 December 2024 without intravenous contrast demonstrated a 16-mm PI-RADS 5 lesion located at the junction of the base and mid-gland of the left peripheral zone (Fig. 1). The examination was repeatedly interrupted by the patient, resulting in limited diagnostic quality (PI-QUAL version 2 score 1) and incomplete image acquisition.2 No definite extracapsular extension or seminal vesicle invasion was identified. Enlarged left external iliac lymph nodes measuring up to 13 mm and para-aortic lymph nodes were considered suspicious for metastatic involvement.
Fig. 1.
Baseline multiparametric prostate MRI performed on 9 December 2024.
(A) Axial prostate MRI demonstrating a 16-mm PI-RADS 5 lesion within the left peripheral zone.
(B) Axial pelvic MRI demonstrating preserved pelvic anatomy without radiological evidence of extracapsular extension.
(C) Corresponding prostate MRI confirming the suspicious lesion. Image quality was limited by motion artefacts, resulting in a PI-QUAL version 2 score of 1.
Baseline whole-body bone scintigraphy performed on 17 December 2024 demonstrated degenerative tracer uptake involving multiple joints together with possible inflammatory activity within the maxillary sinuses. No evidence of osteoblastic skeletal metastases was identified (Fig. 2).
Fig. 2.
Baseline whole-body bone scintigraphy performed on 17 December 2024.
(A) Anterior whole-body bone scintigraphy demonstrating physiological tracer distribution with degenerative uptake in multiple joints and no evidence of osteoblastic skeletal metastases.
(B) Posterior whole-body bone scintigraphy confirming the absence of osteoblastic skeletal metastases.
MRI–ultrasound fusion-guided biopsy performed on 24 December 2024 demonstrated no evidence of malignancy.
Beginning in January 2025, the patient developed progressively worsening diffuse bone pain, predominantly involving the axial skeleton. Metastatic disease was considered unlikely because baseline bone scintigraphy was negative and the observed tracer uptake was interpreted as degenerative. During follow-up, PSA increased dramatically to 820 ng/mL in April 2025 and reached 1244 ng/mL by 30 April 2025. Laboratory investigations demonstrated elevated alkaline phosphatase and anaemia, consistent with extensive skeletal involvement.
Repeat multiparametric prostate MRI performed in May 2025 was again prematurely terminated at the patient's request. The previously identified 16-mm PI-RADS 5 lesion remained essentially unchanged. Enlarged pelvic and para-aortic lymph nodes persisted. In contrast to the baseline examination, numerous osseous lesions with imaging characteristics consistent with metastatic disease became evident within the acquired field of view, prompting immediate repeat skeletal staging (Fig. 3).
Fig. 3.
Follow-up multiparametric prostate MRI performed in May 2025.
(A) Axial pelvic MRI demonstrating multiple osseous lesions within the pelvis suspicious for metastatic disease.
(B) Axial prostate MRI demonstrating the persistent PI-RADS 5 lesion within the left peripheral zone with no substantial interval progression of the primary tumour.
Repeat MRI–ultrasound fusion-guided biopsy confirmed Grade Group 5 prostate adenocarcinoma (Gleason score 4 + 5 = 9) with cribriform architecture and perineural invasion. Four of seven targeted cores contained carcinoma, with a total tumour length of 5 mm in 80 mm of sampled tissue (6%).
Repeat whole-body bone scintigraphy demonstrated extensive osteoblastic metastases involving the skull, ribs, thoracic and lumbosacral spine, pelvis, scapulae, humeri, and proximal femora. The imaging pattern was consistent with an oncologic superscan and high-volume metastatic disease, representing marked progression compared with the examination performed five months earlier (Fig. 4).
Fig. 4.
Follow-up whole-body bone scintigraphy performed in May 2025.
(A) Anterior whole-body bone scintigraphy demonstrating diffuse osteoblastic skeletal metastases involving the axial and appendicular skeleton.
(B) Posterior whole-body bone scintigraphy demonstrating an oncologic superscan consistent with high-volume metastatic disease.
A chronological summary of the patient's clinical course, PSA kinetics, imaging findings, and histopathological results is presented in Table 1.
Table 1.
Clinical timeline of disease progression from initial diagnosis to diffuse skeletal metastases.
| Date | Event |
|---|---|
| 02 Dec 2024 | PSA 35 ng/mL |
| 09 Dec 2024 | Prostate MRI: 16-mm PI-RADS 5 lesion |
| 17 Dec 2024 | Bone scintigraphy: no skeletal metastases |
| 24 Dec 2024 | MRI–ultrasound fusion-guided biopsy: benign histopathological findings |
| Jan 2025 | Progressive diffuse bone pain |
| Apr 2025 | PSA 820 ng/mL |
| 30 Apr 2025 | PSA 1244 ng/mL |
| May 2025 | Repeat MRI: stable index lesion with multiple osseous lesions suspicious for metastatic disease |
| May 2025 | Repeat fusion biopsy: Grade Group 5, Gleason 4 + 5 = 9 |
| May 2025 | Repeat bone scintigraphy: oncologic superscan (high-volume metastatic disease) |
3. Discussion
This case illustrates an exceptionally aggressive clinical course of prostate adenocarcinoma, characterized by progression from negative whole-body bone scintigraphy to an oncologic superscan within only five months. During the same period, PSA increased from 35 ng/mL to 1244 ng/mL despite minimal radiological progression of the primary prostate lesion, highlighting the biological heterogeneity of high-grade prostate cancer.
Bone scintigraphy remains the conventional imaging modality for skeletal staging in prostate cancer. However, because it detects osteoblastic activity rather than tumour cells directly, its sensitivity may be limited in the early stages of metastatic disease, and degenerative skeletal changes may further complicate image interpretation.3 In the present case, baseline bone scintigraphy demonstrated only degenerative tracer uptake, whereas repeat prostate MRI revealed numerous osseous lesions suspicious for metastatic disease before diffuse skeletal involvement was confirmed by repeat bone scintigraphy. This sequence illustrates the limitations of conventional skeletal imaging in rapidly progressive disease.
Rapid PSA kinetics represent an important indicator of tumour aggressiveness. PSA velocity and PSA doubling time have been associated with disease progression and adverse oncological outcomes, particularly in metastatic prostate cancer.4,5 Patients presenting with PSA concentrations exceeding 1000 ng/mL usually have advanced metastatic disease and poor prognosis, and recent evidence suggests that PSA response metrics such as PSA 90 may provide additional prognostic information in this population.6,7 In our patient, the dramatic rise in PSA preceded widespread skeletal dissemination despite minimal radiological change in the primary tumour, emphasizing that disproportionate PSA escalation should prompt immediate repeat staging regardless of previous imaging findings.
The initially negative MRI–ultrasound fusion-guided biopsy represents an additional important aspect of this case. A negative targeted biopsy does not exclude clinically significant prostate cancer when a highly suspicious PI-RADS 5 lesion persists, particularly in the setting of markedly elevated or rising PSA. Previous studies have demonstrated clinically significant prostate cancer on repeat biopsy in a substantial proportion of men with persistent PI-RADS 4/5 lesions after an initially negative targeted biopsy.8 Such discordance between imaging, biochemical findings, and histopathology should therefore prompt close clinical and PSA follow-up and consideration of early repeat biopsy. In our patient, repeat biopsy ultimately confirmed Grade Group 5 prostate adenocarcinoma, emphasizing the potential for sampling error even with MRI-targeted biopsy and the importance of reassessment when clinical suspicion remains high.
Histopathological examination confirmed Grade Group 5 prostate adenocarcinoma with cribriform architecture and perineural invasion, both well-established adverse prognostic features associated with metastatic progression and disease-specific mortality.9,10 Notably, tumour involvement represented only 6% of the total sampled tissue, whereas the patient already had diffuse skeletal metastases. This discordance suggests that tumour volume within biopsy cores may not accurately reflect systemic disease burden in biologically aggressive prostate cancer.
Progression from negative skeletal staging to an oncologic superscan within five months appears exceptionally uncommon, even in Grade Group 5 disease. This rapid evolution may reflect either occult skeletal metastases below the detection threshold of conventional bone scintigraphy at initial staging or an unusually aggressive metastatic phenotype with accelerated osteoblastic dissemination. Clinically, this case highlights the importance of maintaining a high index of suspicion and performing early repeat staging in patients with rapidly rising PSA levels and new skeletal symptoms despite previously negative skeletal imaging.
4. Conclusion
This case describes exceptionally rapid progression from negative whole-body bone scintigraphy to an oncologic superscan within five months in a patient with Grade Group 5 prostate adenocarcinoma. Despite minimal radiological progression of the primary prostate lesion, the patient developed explosive PSA elevation and diffuse osteoblastic skeletal metastases, emphasizing the aggressive biological behaviour of a subset of prostate cancers.
Clinically, rapidly rising PSA levels accompanied by new skeletal symptoms should prompt immediate repeat staging, even after recent negative bone scintigraphy. Early reassessment using more sensitive imaging modalities should be considered when clinical suspicion of metastatic progression persists despite initially negative conventional skeletal imaging.
CRediT authorship contribution statement
Bartłomiej Olczak: Writing – review & editing, Writing – original draft, Investigation, Data curation, Conceptualization. Katarzyna Sklinda: Writing – review & editing, Investigation, Formal analysis. Radoslaw Szostek: Writing – review & editing, Supervision, Investigation. Marek Kasprowicz: Writing – review & editing, Investigation. Michał Małek: Writing – review & editing, Supervision. Łukasz Michałowski: Writing – review & editing, Methodology, Investigation. Jerzy Walecki: Writing – review & editing, Supervision. Jan Bociański: Writing – review & editing, Resources, Investigation.
Ethics declaration
Written informed consent to take part in the study and to publish the article has been obtained from all participants or their legal representatives. The privacy rights of participants have been observed.
This study was performed in compliance with relevant laws, regulatory frameworks and guidelines where the research took place. Ethics committee approval was not required under relevant laws and institutional guidelines. Ethics committee approval was not required for this single-patient case report. Written informed consent for publication was obtained from the patient.
This research follows the CARE guidelines and the CARE checklist.
Patient consent
Written informed consent for publication of this case report and accompanying images was obtained from the patient.
References
- 1.Askari E., Shakeri S., Roustaei H., et al. Superscan pattern on bone scintigraphy: a comprehensive review. Diagnostics (Basel) 2024 Oct 6;14(19):2229. doi: 10.3390/diagnostics14192229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.de Rooij M., Allen C., Twilt J.J., et al. PI-QUAL version 2: an update of a standardised scoring system for the assessment of image quality of prostate MRI. Eur Radiol. 2024 Nov;34(11):7068–7079. doi: 10.1007/s00330-024-10795-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Mohseninia N., Zamani-Siahkali N., Harsini S., et al. Bone metastasis in prostate cancer: bone scan versus PET imaging. Semin Nucl Med. 2024 Jan;54(1):97–118. doi: 10.1053/j.semnuclmed.2023.07.004. [DOI] [PubMed] [Google Scholar]
- 4.Vickers A.J., Brewster S.F. PSA velocity and doubling time in diagnosis and prognosis of prostate cancer. Br J Med Surg Urol. 2012 Jul 1;5(4):162–168. doi: 10.1016/j.bjmsu.2011.08.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Lin Y.C., Lin P.H., Shao I.H., et al. Prostate-specific antigen kinetics effects on outcomes of low-volume metastatic prostate cancer patients receiving androgen deprivation therapy. J Oncol. 2021;2021 doi: 10.1155/2021/9648579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Kan H.C., Hou C.P., Lin Y.H., et al. Prognosis of prostate cancer with initial prostate-specific antigen >1,000 ng/mL at diagnosis. OncoTargets Ther. 2017 Jun 12;10:2943–2949. doi: 10.2147/OTT.S134411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Sato R., Yoshimi Y., Nishio T., et al. Clinical outcomes and prognostic significance of PSA90 in patients with prostate cancer and initial PSA >1,000 ng/mL at diagnosis. Cancer Diagn Progn. 2025 Nov-Dec;5(6):741–747. doi: 10.21873/cdp.10489. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Kornienko K., Reuter M., Maxeiner A., et al. Follow-up of men with a PI-RADS 4/5 lesion after negative MRI/Ultrasound fusion biopsy. Sci Rep. 2022 Aug 10;12(1) doi: 10.1038/s41598-022-17260-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Osiecki R., Kozikowski M., Sarecka-Hujar B., et al. Prostate cancer morphologies: cribriform pattern and intraductal carcinoma relations to adverse pathological and clinical outcomes—systematic review and meta-analysis. Cancers (Basel) 2023 Feb 21;15(5):1372. doi: 10.3390/cancers15051372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Kweldam C.F., Wildhagen M.F., Steyerberg E.W., et al. Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer. Mod Pathol. 2015 Mar;28(3):457–464. doi: 10.1038/modpathol.2014.116. [DOI] [PubMed] [Google Scholar]