Abstract
Background:
Synchronous occurrence of prostate cancer (PCa) and renal cell carcinoma (RCC) is uncommon. RCC has a higher tendency to metastasize to the adrenal glands, renal hilar, and retroperitoneal lymph nodes compared to PCa. To date, there are no documented cases existing where metastatic tumors in these regions, observed in patients concurrently with PCa and RCC, have originated from the PCa rather than the RCC.
Case presentation:
In this case report, we described a 67-year-old male presented with dysuria for two months and left lower extremity edema for three days. Percutaneous biopsies revealed synchronous primary RCC and PCa. However, the origin of the metastatic tumors, especially those involving the adrenal glands, renal hilum, and retroperitoneal regions, remained undetermined. Subsequent surgical procedures identified that the metastatic lesions originated from the PCa, while the RCC was localized. Ultimately, the patient with metastatic hormone-sensitive prostate cancer (mHSPC) received combination therapy with rezvilutamide and goserelin, which resulted in a satisfactory treatment response.
Conclusion:
In patients with concurrent PCa and RCC, metastatic lesions in the adrenal glands, renal hilar, and retroperitoneal lymph nodes may also originate from the PCa. Accurate identification of the primary tumor and proper staging are critical for the appropriate management of patients with multiple primary malignancies with concurrent metastases.
1 Introduction
Prostate cancer (PCa) and renal cell carcinoma (RCC) are common tumors of the urinary system, with respective incidence rates of 7.3% and 2.2% in overall tumor landscape (1). However, the synchronous occurrence of RCC and PCa is rare (2). Most of the previous studies only reported the use of combined radical prostatectomy and partial nephrectomy as a treatment for synchronous, localized PCa and RCC (3). However, the metastatic patterns and treatment approaches for patients with coexisting PCa and RCC with metastases remain elusive owing to a lack of research. In patients with PCa, the predominant metastatic sites include the bone, lymph node, and liver (4), while RCC predominantly involves the lung, lymph node, and bone (5). In PCa, the metastatic potential to the kidney or adrenal gland is approximately 1.0%, with retroperitoneal lymph node involvement occurring in about 1.8% of cases (4). In RCC, the incidence of adrenal gland metastasis ranges from 6% to 10% (5), and the incidence of lymph node metastasis is 21.8%, with 6.8% occurring in the retroperitoneum (6). Notably, RCC exhibits a markedly higher frequency of retroperitoneal lymph node and adrenal gland metastases compared to PCa. Here, we present a case of an elderly male patient presenting with concurrent RCC and PCa. Notably, all metastatic lesions, including those in the adrenal gland and the renal hilar region, were determined to have originated from the PCa. To our knowledge, this unique coexistence has not been documented in prior reports.
2 Case presentation
2.1 Medical history and examinations
The patient was a 67-year-old male who presented with a two-month history of dysuria and a three-day history of edema in the left lower extremity. Upon admission, computed tomography (CT) scan (Figure 1A) revealed a 4.0 × 3.8 cm mass in the left kidney and a 4.8 × 4.0 cm mass in the left adrenal gland with irregular enhancement. Concurrently, there was evidence of increased and enlarged lymph nodes throughout multiple sites in the body, as well as irregular enhancement of the prostate and bilateral seminal vesicles. Subsequently, the 18F-FDG PET/CT scan (Figure 1B) identified areas of intense uptake in the seminal vesicles, prostate, left adrenal gland, skeletal regions, and lymph nodes of the cervical, axillary, mediastinal, and abdominal areas, which were indicative of malignancies. However, the precise location of the primary tumor could not be definitively identified. Additionally, the uptake level of the left renal mass was relatively lower than those of the aforementioned lesions but higher than that of normal tissues, suggesting that it might be a primary RCC. The digital rectal examination (DRE) revealed a firm, enlarged prostate with an indurated nodule. The patient’s prostate-specific antigen (PSA) level was 531 ng/ml, with no detected abnormalities in adrenal hormones. Physicians initially considered that the patient might have metastatic PCa (staged as T3bN1M1b), concurrently with RCC (staged as T4N1Mx) that had metastasized to the adrenal gland and retroperitoneal lymph nodes.
Figure 1
2.2 Investigations
To further clarify the original tumors of this patient, we performed an ultrasound-guided percutaneous biopsy of the left renal mass and an ultrasound-guided transperineal biopsy of the prostate. The immunohistochemical results are summarized in Table 1, the pathologic diagnoses were primary clear cell renal cell carcinoma (ccRCC) and primary adenocarcinoma of prostate with a Gleason score of 4 + 4 = 8. Subsequently, the patient underwent a left nephrectomy, left adrenalectomy, and lymph node dissection of the left renal hilum and retroperitoneum region (Supplementary Figure 1). The immunohistochemical results of the resected specimens are summarized in Table 1. The renal mass was further confirmed as ccRCC with an International Society of Urological Pathology (ISUP) grade of 3, while the lesions of the adrenal glands, renal hilar lymph nodes and retroperitoneal lymph nodes were originated from PCa. The RCC was staged as T1N0M0, while the stage of PCa was determined to be T3bN1M1c.
Table 1
| Antigens (markers) | Needle biopsy | Resected specimen | |||
|---|---|---|---|---|---|
| Renal mass | Prostate | Renal mass | Adrenal mass/ Retroperitoneal lymph nodes | Renal hilar lymph nodes | |
| PAX-8 | + | – | + | – | – |
| NKX3.1 | NA | + | NA | + | + |
| CD10 | + | NA | + | NA | NA |
| CA IX | + | NA | + | NA | NA |
| CK7 | – | NA | – | NA | NA |
| AMACR | NA | + | NA | NA | NA |
| P63 | NA | – | NA | NA | NA |
| PSA | NA | + | NA | NA | NA |
| PSMA | NA | + | NA | + | NA |
| CgA | NA | – | NA | +, 5% | NA |
| Syn | NA | NA | NA | – | NA |
| SF-1 | NA | NA | NA | – | NA |
| TTF-1 | NA | NA | NA | – | NA |
Immunohistochemical results of the needle biopsy and resected specimens.
NA, not available; PAX-8, paired box gene 8; NKX3.1, NK3 homeobox 1; CD10, cluster of differentiation 10; CA IX, carbonic anhydrase IX; CK7, cytokeratin 7; AMACR, alpha-methylacyl-CoA racemase; HCK, hematopoietic cell kinase; PSA, prostate-specific antigen; PSMA, prostate-specific membrane antigen; CgA, chromogranin A; Syn, synaptophysin; SF-1, steroidogenic factor 1; TTF-1, thyroid transcription factor.
+, the result of immunohistochemical staining is positive; -, the result of immunohistochemical staining is negative.
2.3 Treatment and outcome
Given the diagnosis of high-risk metastatic hormone-sensitive prostate cancer (mHSPC), the patient was treated with rezvilutamide and goserelin acetate sustained-release depot combination therapy. The CT scans performed at one and three months after treatment showed that all metastatic lesions were shrinking, with no signs of recurrence of RCC (Figure 2A; Supplementary Figure 2). Follow-up PSA levels, measured at one, three, and six months after treatment, were 144 ng/ml, 0.78 ng/ml, and 0.09 ng/ml, respectively (Figure 2B). Additionally, radionuclide bone scintigraphy did not detect any new lesions. The therapeutic outcomes substantiated that all metastatic lesions demonstrated a significant response to hormonal therapy.
Figure 2
3 Discussion
In this case report, we described for the first time a patient with concurrent PCa and RCC in whom the adrenal, renal hilar, and retroperitoneal lymph nodes, as well as other metastatic sites, were derived from PCa, not RCC. The patient was ultimately diagnosed with localized RCC and high-risk mHSPC with metastases to the left adrenal gland, bones, and multiple distant lymph nodes.
The synchronous occurrence of RCC and PCa is uncommon. Data from previous studies showed that the incidence of patients diagnosed with both PCa and RCC ranged from 0.83% to 2.10%, while the rate of synchronous occurrence was even lower (7–10). Meanwhile, metastasis from prostate cancer to the kidney has also been observed in case reports (11, 12), which is extremely rare but actually exists. Furthermore, two cases of retroperitoneal lymph node metastases containing both RCC and PCa, a phenomenon known as ‘collision metastasis’, have been reported in previous studies (13, 14). Therefore, the co-existence of RCC and PCa presents a complex diagnostic and therapeutic challenge. Lymph nodes are a common site of metastasis for both PCa and RCC, but the involvement of retroperitoneal lymph nodes is an uncommon presentation in PCa (15). Metastases to the perirenal tissues are exceedingly rare (16, 17). However, in patients with concurrent RCC and PCa, the retroperitoneal lymph node metastases may not always originate from the RCC. Furthermore, although the incidence of adrenal metastasis in metastatic RCC (8.9%, 991/11157) (6) is higher than that in metastatic PCa (1.9%, 12/620) (18), both possibilities remain. Therefore, for patients presenting with synchronous RCC and PCa, biopsies are essential for determining the origin of metastatic lesions.
Previously, 16 cases of adrenal metastasis from PCa have been reported (19–32), which were summarized in Table 2. All patients had high Gleason scores. Adrenal metastases from prostate cancer occurred predominantly in patients with mCRPC, and only 2 patients reported adrenal metastases in patients with mHSPC (24, 26). In the reported cases, common specific symptoms were absent, though abdominal pain could be a possible exception in cases of large tumors. More than half of the patients (10/16) underwent adrenalectomy, with the majority experienced disease remission after surgery, especially those with isolated adrenal metastases. Among these cases, no patients had concomitant renal mass or renal hilar lymph node metastasis.
Table 2
| Study | Initial characteristics | Post-adrenal metastasis discovery | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age | Symptoms | Gleason score | PSA (ng/ml) | Tumor type | Surgery | Radiation therapy | Other treatments for mPCa | PSA (ng/ml) | Stages of patients | Site of adrenal metastases | Maximum diameter of adrenal metastases | Other sites of metastasis | Treatment for mPCa | Special treatment for adrenal metastases | Outcome | |
| Topal 2024 (19) | 66 | NA | NA | NA | NA | NA | NA | Chemotherapy (docetaxel) | 61.9 | mCRPC | Bilateral | NA | No | NA | 4 cycles (4 × 7.4 Gbq) of 177Lu-PSMA-617 at 6–8 weeks intervals | Post-treatment PSA levels dropped to 0.3 ng/mL and further decreased to 0.084 ng/mL at 6 months. |
| Sakellakis, 2023 (20) | 60 | No symptoms | 5+4 = 9 | NA | Adenocarcinoma | RP with LND | Yes | Leuprolide | 63.6 | mCRPC | Left | 5.0 cm | No | Leuprolide | Left adrenalectomy | Nadir PSA was 0.7 ng/mL post-operatively, but it eventually increased to 28.5 ng/mL, with a local recurrence in the left suprarenal area within 21 months. |
| 70 | Intermittent hematuria | 4+4 = 8 | 9.4 | Adenocarcinoma | No | No | Leuprolide | 0.6 | mCRPC | Right | 2.7 cm | No | Leuprolide | Right adrenalectomy | PSA remained undetectable for 15 months. | |
| 60 | No symptoms | 3+4 = 7 | 6.7  | Adenocarcinoma | RP | Yes | Leuprolide; Bicalutamide; Abiraterone acetate plus prednisone | NA | mCRPC | Right | NA | Bone; Retroperitoneal LN | Enzalutamide; Diethylstilbesterol | Right adrenalectomy | PSA increased after 5 months. | |
| Kanatsız 2023 (21) | 61 | NA | 4+5 = 9 | NA | Adenocarcinoma | RP | Yes | Chemotherapy; ADT | NA | mCRPC | Bilateral | Right: 4.0 cm Left: 3.2 cm | No | NA | NA | NA |
| Soriano 2022 (22) | 86 | NA | 8 | NA | mPCa with hepatoid differentiation | RP | Yes | Goserelin; Bicalutamide; Abiraterone and zolendronic; Enzalutamide | 16.11 | mCRPC | Left | 2.9 cm | Bone; Retrocrural and retroperitoneal LN | Chemotherapy (cabazitaxel) | No | NA |
| Zhao 2022 (23) | 65 | NA | 4+5 = 9 | 387.2 | Adenocarcinoma | RP with LND | Yes | ADT | 54.7 | mCRPC | Bilateral | NA | No | Chemotherapy (docetaxel) and ADT | No | PSA level decreased to 6.6 ng/mL after 7 courses of docetaxel, and the bilateral adrenal masses reduced within 9 months. |
| Ribeiro 2022 (24) | 68 | NA | 4+5 = 9 | NA | Adenocarcinoma | RP | Yes | No | 1.97 | mHSPC | Left | NA | No | Systemic treatment | No | PSA level decreased significantly. |
| Muñoz López 2022 (25) | 68 | Acute urinary retention | NA | 3.7 | Neuroendocrine carcinoma | Bipolar transurethral resection | No | ADT plus chemotherapy | NA | mCRPC | Bilateral | Right: 12 cm Left: 12.5 cm | No | NA | Bilateral adrenalectomy | The patient remains alive with no reported deterioration during follow-up. |
| McGeorge 2021 (26) | 79 | NA | 4+5 = 9 | NA | NA | No | Yes | No | 5.2 | mHSPC | Right | 2.2 cm | Lung | Goserelin | No | Confirmed castrate-resistance |
| ↓ (ADT) ↓ | ↓ | ↓ | ||||||||||||||
| 18.0 | mCRPC | Right | 4.3 cm | No | Right adrenalectomy | PSA initially dropped to 0.09 ng/ml after surgery but rose to 1.6 ng/mL within 12 months, with metastases to para-aortic and inferior mediastinal lymph nodes. | ||||||||||
| Ashrafi 2020 (27) | 77 | Vague abdominal discomfort | NA | 11 | Adenocarcinoma | RP | NA | ADT | 1.0 | mCRPC | Left | 5.9 cm | No | ADT | Left adrenalectomy | At 5 years follow-up, PSA levels remained undetectable. |
| Matrone 2015 (28) | 69 | NA | 3+5 = 8 | 459.6 | NA | No | Yes | ADT | 106.8 | mCRPC | Right | 3.5 cm | External iliac LN | Triptorelin | Right adrenalectomy | Post-treatment PSA levels dropped to 0.76 ng/mL and further decreased to 0.01 ng/mL at 10 months. |
| Subhawong 2010 (29) | 71 | NA | 5+5 = 10 | 23 | Adenocarcinoma | No | Yes | ADT; Anti-androgens; Ketoconazole; Hydrocortisone | 27.0 | mCRPC | Left | 12.0 cm | Retroperitoneal LN | No | Left adrenalectomy | After surgery, the patient's PSA declined to normal range without requiring adjuvant therapy. |
| Barrisford 2009 (30) | 39 | Lower back pain | 4+5 = 9 | 40 | Adenocarcinoma | RP and LND | Yes | Neoadjuvant leuprolide; Leuprolide acetate and bicalutamide; Ketoconazole | 151.4 | mCRPC | Left | 6.8 cm | No | Leuprolide | Left adrenalectomy (only resect the bulk of the tumor) | The PSA was 17.8 ng/mL one month postoperative, but began to rise at the sixth week. |
| Kawahara 2009 (31) | 65 | Increased urinary frequency | 4+3 = 7 | 515 | NA | No | No | Maximum androgen blockade; Dexamethasone plus docetaxel | NA | mCRPC | Bilateral | NA | Bone; Pleural | NA | NA | NA |
| Sakamoto 1999 (32) | 64 | NA | NA | 1020 | Adenocarcinoma | No | No | ADT | 3.3 | mCRPC | Left | 2 cm | Bone; Lung | Adjuvant chemotherapy (vinblastine and estramustine); LH-RH agonist plus UFT | Left adrenalectomy | After surgery, PSA levels dropped below 0.1 ng/mL, and no disease progression was observed with LH-RH agonist and UFT treatment. |
Summary of reported prostate cancer cases with adrenal metastases.
PSA, prostate-specific antigen; NA, not available; RP, radical prostatectomy; LND, lymph node dissection; mPCa, metastatic prostate cancer; mCRPC, metastatic castration-resistant prostate cancer; mHSPC, metastatic hormone-sensitive prostate cancer; ADT, androgen deprivation therapy; LN, lymph node; LH-RH agonist, luteinizing hormone-releasing hormone agonist; UFT, mixture of tegafur and uracil.
↓, changes in the disease status, treatment plan, and clinical outcomes.
DRE and PSA screening are the most common prostate cancer screening methods. Despite PSA screening can lead to overdiagnosis and potential overtreatment in early low-risk prostate cancer, PSA screening remains crucial (33). Previous studies have revealed a low coverage of PSA screening in most Asian countries (34). This patient, for instance, had never undergone PSA screening or a DRE, presenting with widespread metastatic disease at initial diagnosis, which underscores the critical nature of prostate cancer screening.
The treatment methods for metastatic RCC and metastatic PCa are distinct. The common first-line treatments for advanced or metastatic RCC include single-agent targeted therapy or immune checkpoint inhibitor (ICI)-based combination therapy (35). In contrast, the treatment approaches for high-risk mHSPC typically involve combination therapies based on androgen deprivation therapy (ADT) (36). Hence, the accurate staging of both RCC and PCa as well as the identification of the primary tumor is of great importance. In this case, the RCC is small with the ISUP grade of 3, while the perinephric lymph nodes and adrenal metastases all originating from the prostate. Consequently, the patient was diagnosed with localized RCC coexisting with high-risk mHSPC. After receiving combination therapy based on ADT, there was a significant reduction in all metastatic lesions, resulting in stable disease management. Therefore, in cases with multiple primary malignancies, the accurate staging of different tumors is crucial for the success of the treatment.
4 Conclusion
In this case, conventional radiological and nuclear medicine examinations proved insufficient to determine the primary site of the tumor and accurately stage the malignancies. Percutaneous biopsies confirmed the presence of two synchronous tumors. Subsequent pathological analysis of the surgically removed tissues identified the origin of the metastasis and accurately staged the patient’s renal and prostate cancers, leading to a more favorable therapeutic response. This case highlights that metastatic lesions in the adrenal gland and renal hilar lymph nodes may not exclusively originate from the RCC but could also arise from the PCa in the context of concurrent RCC and PCa.
Statements
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.
Ethics statement
The studies involving humans were approved by Ethics Committee of West China Hospital, Sichuan University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
YZ: Data curation, Formal analysis, Investigation, Writing – original draft. JC: Methodology, Project administration, Writing – original draft. LX: Data curation, Writing – original draft. XH: Conceptualization, Data curation, Writing – review & editing. HZ: Funding acquisition, Resources, Supervision, Writing – review & editing. ZL: Project administration, Supervision, Writing – review & editing.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Natural Science Foundation of China (NSFC 82172785 and 81974398).
Acknowledgments
The authors would like to express their sincere gratitude to the patient and their family for their trust, invaluable assistance, collaborative engagement, and consent to participate in this research.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2024.1412067/full#supplementary-material
Abbreviations
PCa, prostate cancer; RCC, renal cell carcinoma; ADT, androgen deprivation therapy; DRE, digital rectal examination; mHSPC, metastatic hormone-sensitive prostate cancer; CT, computed tomography; PSA, prostate-specific antigen; ccRCC, clear cell renal cell carcinoma; AR, androgen receptor; ICI, immune checkpoint inhibitor.
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Summary
Keywords
multiple primary cancers, renal cell carcinoma, prostate cancer, metastatic tumor, adrenal metastasis, lymph node metastasis, surgical diagnostic procedures
Citation
Zhang Y, Chen J, Xu L, Hu X, Zeng H and Liu Z (2024) Case report: Synchronous prostate cancer and renal cell carcinoma with prostate cancer-origin metastases to adrenal and renal hilar lymph nodes. Front. Oncol. 14:1412067. doi: 10.3389/fonc.2024.1412067
Received
08 April 2024
Accepted
18 September 2024
Published
07 October 2024
Volume
14 - 2024
Edited by
Ronald M. Bukowski, Cleveland Clinic, United States
Reviewed by
Xiaobo Wu, The Chinese University of Hong Kong, China
Chunguang Yang, Huazhong University of Science and Technology, China
Updates
Copyright
© 2024 Zhang, Chen, Xu, Hu, Zeng and Liu.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Zhenhua Liu, zhliu@scu.edu.cn
†These authors have contributed equally to this work and share first authorship
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.