Cytoreductive prostatectomy after platinum–etoposide chemotherapy in de novo metastatic prostatic small cell neuroendocrine carcinoma

A 50-year-old man walked into a hospital in Chengdu, China, in June 2022 with a problem that seemed routine: he could not urinate. He had endured progressive pain while urinating for more than a year, and on the day of admission he had developed acute urinary retention. The available local-hospital evaluation showed a serum PSA level of 2.06 ng/mL, a value well within the normal reference range, prostatic enlargement on digital rectal examination, and a prostate volume of 93 cm³ on ultrasonography. Pelvic MRI revealed an enlarged prostate with heterogeneous signal intensity and multiple enlarged lymph nodes along the bilateral iliac vessels and within the pelvis. Nothing about the presentation suggested the extraordinary rarity of what was actually growing inside him.

Surgeons at the local hospital performed a transurethral resection of the prostate, or TURP, as a deobstructive procedure to relieve the retention and persistent voiding difficulty rather than as definitive cancer surgery. Histopathologic examination of the resected tissue initially suggested prostatic adenocarcinoma, prompting referral to Chinese People’s Liberation Army Western Theater General Hospital for further evaluation. But when pathologists there reviewed the TURP specimen on June 27, 2022, the morphologic and immunohistochemical features told a very different story. The tumor cells showed small-cell morphology together with strong expression of the neuroendocrine markers synaptophysin, chromogranin A, and CD56, and a Ki-67 proliferation index of approximately 50 percent. The immunophenotype was androgen receptor negative, PSA negative, p63 negative, and P504S positive, with focal CK7 positivity and negative stains for CDX2, CK20, CK5/6, and CK20. The diagnosis was small cell neuroendocrine carcinoma of the prostate, or SCNEC, a poorly differentiated and rapidly progressive form of neuroendocrine prostate cancer that is extraordinarily rare as a de novo primary malignancy.

A SEER database analysis identified only 309 cases of de novo primary neuroendocrine prostate cancer among 510,913 prostate cancers diagnosed between 1973 and 2003, an incidence of just 0.06 percent, of which 186 cases, or 60.2 percent, had small-cell histology. Conventional acinar adenocarcinoma accounts for the great majority of prostatic malignancies, and de novo primary neuroendocrine prostate cancer is so uncommon that most urologists will never encounter a single case in their careers. The 2022 WHO classification of urinary and male genital tumours recognizes well-differentiated neuroendocrine tumours, small cell and large cell neuroendocrine carcinomas, and mixed neuroendocrine neoplasms within its genitourinary neuroendocrine taxonomy, and also recognizes treatment-related neuroendocrine prostatic carcinoma as a distinct prostatic tumour type. Outcomes for patients with metastatic prostatic small-cell carcinoma are grim: a retrospective case series treated with chemotherapy reported a median survival of only 9.4 months after diagnosis, while a population-based cohort of 191 patients reported observed survival rates of 47.9 percent at 12 months and just 14.3 percent at 60 months.

Staging imaging after the TURP raised further diagnostic complexity. On July 1, 2022, 18F-FDG PET/CT showed heterogeneous prostatic uptake, possible seminal vesicle involvement, FDG-avid pelvic and systemic lymph nodes, and scattered bilateral pulmonary nodules without abnormal uptake or a dominant pulmonary mass. Possible distal right ureter involvement with hydronephrosis was also reported. The clinical team documented T4N1M1c disease, although the T4 classification reflected suspected adjacent-organ involvement and the M1c category reflected clinically suspected, unbiopsied pulmonary metastases; neither was histologically confirmed. The pulmonary nodules created a genuine diagnostic dilemma, because pulmonary small-cell carcinoma metastatic to the prostate remained a differential diagnosis. A prostatic primary was favored because the presenting symptoms and dominant mass effect arose from the prostate, the patient had no smoking history and no pulmonary symptoms, and PET/CT showed multiple scattered non-FDG-avid pulmonary nodules without a dominant pulmonary mass. A biopsy of the pulmonary nodules was recommended but declined by the patient. TTF-1 positivity in the tumor, often considered a marker of pulmonary origin, was not used as a stand-alone diagnostic criterion; TTF-1 may be expressed in extrapulmonary small-cell carcinomas and was positive in 23 of 44 prostatic small-cell carcinomas, or 52.3 percent, in a large pathologic series. The integrated clinicopathologic diagnosis was therefore de novo primary prostatic SCNEC with clinically suspected pulmonary metastases, although a pulmonary primary could not be excluded with absolute certainty in the absence of histologic sampling of the lung lesions.

Because prospective trials are lacking, the treatment paradigm for prostatic SCNEC is largely extrapolated from small-cell lung cancer, given the biological similarity between the two histologies. Platinum-based chemotherapy combined with etoposide is commonly used in this setting. The patient began treatment with etoposide plus cisplatin, or EP, on June 30, 2022, receiving etoposide 100 mg/m²/day and cisplatin 25 mg/m²/day intravenously on days 1 through 3 of each 28-day cycle. The chemotherapy course was intermittently complicated by nausea, vomiting, and dysphagia, which resolved with supportive care without the need for dose reduction or treatment delay. Serial pelvic MRI scans showed a marked local radiographic response: by October 20, after five cycles, no definite enhancing focus was seen in most of the prostate, although residual urethral enhancement and small pelvic nodes remained. A biopsy on October 24 still showed poorly differentiated carcinoma, confirming that viable tumor persisted despite the dramatic radiographic regression. After seven cycles, pelvic MRI on December 27 showed persistent right peripheral-zone diffusion restriction and residual disease. Ultrasonography in February 2023 estimated a prostate volume of 17 cm³, compared with 72 cm³ measured at the same institution before treatment, an approximately 76 percent reduction. However, because serial target-lesion measurements and comprehensive restaging were not performed, a RECIST 1.1 response category of partial response or stable disease could not be assigned retrospectively.

After seven EP cycles, marked local radiographic response had been achieved but persistent disease remained. At the patient’s own strong request, a multidisciplinary team considered surgery for local control, weighing his age, good performance status, persistent tumor burden, obstructive symptoms, and preference for local treatment. The stated goals were to relieve obstruction, reduce bleeding risk, and decrease local tumor burden; no survival benefit was established. Laparoscopic radical prostatectomy was completed on February 14, 2023, without intraoperative complications, although marked edema and adhesions were encountered. The postoperative course was complicated by a vesicourethral anastomotic leak, which improved after approximately one week of drainage and catheterization. Histopathologic examination of the radical prostatectomy specimen demonstrated both small cell neuroendocrine carcinoma and poorly differentiated non-neuroendocrine adenocarcinoma components, and the tumor was reported as a mixed neuroendocrine–non-neuroendocrine neoplasm, or MiNEN. Vascular and perineural invasion were present, and the Ki-67 proliferation index was 60 to 70 percent. Neither seminal vesicle involvement nor a positive surgical margin was identified. The difference between the TURP and prostatectomy findings most likely reflected sampling limitations of TURP and intratumoral heterogeneity, and a treatment-related shift in component predominance could not be established from this single case.

The patient was readmitted on April 12, 2023, for postoperative reassessment, and two additional postoperative EP cycles were administered on April 20 and May 19. Cystoscopy on April 24 showed no obvious intravesical neoplasm. But on July 18, approximately five months after surgery, painless gross hematuria, renal failure, bilateral hydronephrosis, and anemia led to clot evacuation and right nephrostomy on July 20, with repeat clot evacuation required on July 22 and 24. Non-contrast abdominal CT on July 25 showed an irregular patchy hypo- and isodense area in the prostatectomy bed with an indistinct boundary from the adjacent posterior bladder wall, blurred surrounding fat planes, and mild thickening of the adjacent pelvic-floor fascia, along with multiple lymph nodes in the left retroperitoneal and abdominopelvic regions. These findings raised suspicion of local and nodal recurrence, although recurrence was not pathologically confirmed. Left nephrostomy was completed on July 27 and repeated on August 7 after dislodgement. Because renal impairment made the patient ineligible for further cisplatin, second-line treatment with irinotecan plus carboplatin began on August 8, 2023, with irinotecan 80 mg/m²/day on days 1 and 8 and carboplatin 400 mg/m² on day 2 of each 21-day cycle. A urinary tract infection in September grew Citrobacter freundii resistant to levofloxacin, requiring a change to amikacin combined with minocycline. No formal restaging was available, so an objective response category could not be assigned to the second-line regimen. Clinical deterioration continued, the family chose best supportive care, and the patient died from multiorgan failure in December 2023, approximately 18 months after diagnosis.

The authors of the case report, published in Frontiers in Urology, emphasize that EP can produce substantial but temporary regression in metastatic prostatic SCNEC, as demonstrated by the reduction in prostate volume from 72 to 17 cm³ and the serial MRI findings. However, the response was incomplete, as viable tumor persisted on biopsy and in the prostatectomy specimen, and progression became clinically apparent after only two additional postoperative EP cycles. This temporal pattern may be compatible with acquired platinum resistance, but the absence of serial systemic target-lesion measurements and the intrinsically aggressive biology of SCNEC prevent resistance from being distinguished from rapid natural disease progression in a single case. The authors therefore describe the course as progression after EP exposure rather than definitive proof of drug resistance. Irinotecan plus carboplatin and subsequent single-agent irinotecan did not provide durable clinical disease control. The patient reported that urinary tract obstruction was markedly improved for approximately the first three months after cytoreductive surgery, and that from the start of chemotherapy through approximately three months after surgery he experienced less pain and better overall quality of life than at initial presentation. These benefits were subjective and not durable, and because no validated symptom score or quality-of-life instrument was administered, the magnitude of improvement could not be quantified.

Evidence for radical surgery in metastatic SCNEC is extremely limited. In a SEER analysis of 309 de novo neuroendocrine prostate cancers, 198 cases, or 64.1 percent, were metastatic, and radical prostatectomy was associated with improved survival only in the nonmetastatic subgroup. In an NCDB study of 243 nonmetastatic small-cell carcinomas, radiotherapy and surgery showed no significant overall-survival difference in pure or mixed histology. Among 379 patients with nodal or distant metastatic small-cell carcinoma, only three patients, or 1 percent, underwent radical prostatectomy, precluding a reliable surgical-benefit estimate; chemotherapy, rather than surgery, was associated with longer survival in that cohort. Because these observational cohorts did not provide a reliable metastatic-surgery comparison, and because this single case lacked a counterfactual comparator, the available data cannot quantify any survival benefit from surgery in metastatic patients. Cytoreductive prostatectomy is therefore not an established survival-prolonging treatment for metastatic SCNEC. The role of androgen deprivation therapy also depends on tumor phenotype: pure SCNEC is commonly independent of the androgen receptor pathway and generally does not meaningfully benefit from ADT, while PSA- and AR-negative tumor with normal-range PSA did not provide a strong rationale for ADT activity against the dominant SCNEC phenotype in this case. Peptide receptor radionuclide therapy has demonstrated clinical benefit in selected somatostatin-receptor-positive gastroenteropancreatic neuroendocrine tumours, but these data do not establish efficacy in prostatic SCNEC.

The authors conclude that systemic therapy should remain the priority in metastatic SCNEC, and that surgery, if considered at all, requires carefully selected local-control or palliative indications following multidisciplinary review. Future research should focus on the molecular mechanisms of neuroendocrine differentiation, biomarkers for patient selection, and prospective evaluation of systemic treatment strategies rather than assuming benefit from local surgery. This single case, the authors stress, informs patient selection and counseling without implying that surgery prolonged survival. For a disease that accounts for a vanishingly small fraction of prostate cancers yet carries a median survival measured in months, the case illustrates both the diagnostic uncertainty created by TTF-1 positivity and unbiopsied pulmonary nodules, the marked but incomplete response to platinum-based chemotherapy, the temporary symptom relief that cytoreductive prostatectomy can provide, and the rapid subsequent progression that ultimately defines the natural history of this rare and aggressive malignancy.

Subject of Research: Case Report: cytoreductive prostatectomy after platinum–etoposide chemotherapy for de novo metastatic prostatic small cell neuroendocrine carcinoma

Article Title: Case Report: cytoreductive prostatectomy after platinum–etoposide chemotherapy for de novo metastatic prostatic small cell neuroendocrine carcinoma

Article References: Case Report: cytoreductive prostatectomy after platinum–etoposide chemotherapy for de novo metastatic prostatic small cell neuroendocrine carcinoma. (n.d.). https://doi.org/10.3389/fruro.2026.1934905

Image Credits: AI Generated

DOI: 10.3389/fruro.2026.1934905

Keywords: case report, cytoreductive surgery, etoposide plus cisplatin, neuroendocrine prostate cancer, prostatic small cell neuroendocrine carcinoma, Case, Report, cytoreductive, prostatectomy, platinum, etoposide, chemotherapy