Low-volume nodal disease in early-stage cervical cancer: a case report of favorable outcome without adjuvant therapy

Highlights

• •Isolated micrometastasis detected after extended lymphadenectomy.
• •Adjuvant therapy omitted due to prolonged postoperative infection.
• •No recurrence at 24 months despite omission of adjuvant therapy.
• •Tumor burden may influence prognosis beyond nodal positivity.
• •Multidisciplinary decision-making remains essential in complex cases.

Abstract

Background

Low-volume nodal disease is increasingly detected in early-stage cervical cancer due to sentinel lymph node biopsy and ultrastaging. Although any nodal metastasis is classified as FIGO 2018 stage IIIC and generally warrants adjuvant chemoradiotherapy after radical surgery, the prognostic and therapeutic relevance of isolated micrometastases remains uncertain.

Case presentation

A 58-year-old woman with FIGO 2018 stage IB2 HPV-related squamous cervical carcinoma underwent radical hysterectomy with bilateral adnexectomy and extended pelvic lymphadenectomy. Histopathological ultrastaging identified a single intracapsular micrometastasis in one of 41 pelvic lymph nodes examined (pT1b1 G2 pN1, FIGO IIIC1). Surgical margins and parametria were negative. Adjuvant concurrent chemoradiotherapy was formally indicated; however, severe postoperative wound infection with prolonged delayed healing prevented timely treatment. Given the extended recovery, absence of macrometastatic disease, and isolated micrometastasis without additional high-risk features beyond lymphovascular space invasion, close surveillance was adopted. At nearly 24 months of follow-up, the patient remains clinically, radiologically, and metabolically disease-free.

Conclusion

This case underscores the need for continued investigation into the biological and clinical significance of minimal nodal tumor burden in early-stage cervical cancer. Further prospective data may help refine risk stratification and optimize treatment allocation within established guideline frameworks.

Cervical cancer is a major public health problem, ranking as the fourth most common cause of cancer incidence and mortality among women worldwide (Bray et al., 2024).

Persistent infection with high-risk HPV represents the main etiological factor in cervical carcinogenesis. HPV DNA is detected in approximately 95% of cervical cancers, with HPV types 16 and 18 accounting for the majority of cases (Walboomers et al., 1999).

In patients with early-stage disease, radical surgery represents the mainstay of treatment, whereas definitive concurrent chemoradiotherapy is generally recommended for locally advanced stages. This stage-adapted strategy aims to achieve optimal local control while minimizing treatment-related morbidity (Cibula et al., 2023, Bhatla et al., n.d.). Accurate staging, particularly about lymph node status, is therefore crucial in tailoring treatment strategies and guiding adjuvant therapy. However, the prognostic and therapeutic implications of low-volume nodal disease remain uncertain.

1. Treatment strategy and the prognostic role of lymph node status in cervical cancer

Treatment strategies for cervical cancer are primarily guided by disease stage. In early-stage disease, surgery represents the standard treatment, whereas definitive concurrent chemoradiotherapy is recommended for locally advanced stages (Cibula et al., 2023, Bhatla et al., n.d.).

Lymph node status represents one of the most important prognostic determinants in cervical cancer. Nodal metastases are associated with a significant reduction in disease-free and overall survival, regardless of other clinicopathological factors such as tumor size, depth of stromal invasion, or histological subtype (Delgado et al., 1989, William et al., 2000).

The prognostic relevance of nodal involvement was formally incorporated into the FIGO 2018 staging system. Stage IIIC identifies patients with lymph node metastases and distinguishes pelvic lymph node involvement (stage IIIC1) from para-aortic lymph node involvement (stage IIIC2) (Cibula et al., 2023, Bhatla et al., n.d.). Both macrometastases and micrometastases are included in this staging category.

In patients treated with primary radical surgery, lymph node positivity identifies a high-risk subgroup for recurrence and generally represents an indication for adjuvant concurrent chemoradiotherapy (Cibula et al., 2023, William et al., 2000). Given the central role of lymph node status in staging and treatment allocation, accurate nodal assessment is crucial in early-stage cervical cancer.

2. Low-volume nodal disease: Isolated tumor cells, micrometastases and macrometastases

The introduction of sentinel lymph node biopsy combined with pathological ultrastaging has significantly increased the detection of low-volume nodal disease in patients with early-stage cervical cancer (Cibula et al., 2023, Guani et al., 2020).

Lymph node involvement is categorized as MAC, MIC, or ITC depending on the size of the nodal metastasis according to the American Joint Committee on Cancer (AJCC) recommendations on breast cancer staging (Zhu et al., 2021). It has been recently implemented in the TNM 8, where MAC and MIC are reported as pN1 and ITC as pN0 (Bianchi et al., 2024). Consequently, patients with low-volume nodal disease may be managed similarly to those with MAC involvement, raising concerns regarding potential overtreatment, particularly in the absence of additional high-risk pathological features.

While the adverse prognostic impact of MAC involvement is well established (Delgado et al., 1989, William et al., 2000), the prognostic significance of low-volume nodal disease, has not been clearly established, and its implications for adjuvant treatment remain uncertain (Cibula et al., 2012). Prospective data from the SENTICOL trials showed that patients with low-volume nodal metastases had a disease-free survival comparable to node-negative patients, and that the addition of adjuvant treatment did not significantly modify disease-free survival (Guani et al., 2020).

These findings raise concerns regarding potential overtreatment and highlight the need for careful interpretation of minimal nodal involvement. In this context, clinically documented cases may provide further insight into the natural history and clinical behavior of low-volume nodal metastases.

3. Clinical implications and case presentation

These uncertainties directly affect clinical decision-making in patients with isolated low-volume nodal disease. We report the case of a woman with early-stage cervical cancer in whom a single MIC pelvic lymph node was identified after extended lymphadenectomy. Although adjuvant chemoradiotherapy was indicated based on nodal status, treatment was not administered due to postoperative wound complications. At nearly 24 months of follow-up, the patient remains disease-free.

A 58-year-old postmenopausal woman with severe obesity (BMI ≈ 41.4 kg/m²) and relevant medical comorbidities was referred to our institution for the management of early-stage cervical cancer. Her medical history was notable for impaired glucose tolerance, with persistently elevated fasting glycemia below the diagnostic threshold for diabetes mellitus, and a history of cigarette smoking, having quit several years prior to presentation. No other significant comorbid conditions were reported.

On gynecological examination, the external genitalia and vagina were consistent with a postmenopausal multiparous status. The uterus was anteverted, of normal size, mobile, and non-tender. Adnexa were not palpable. The cervix appeared enlarged at the level of the anterior fornix, extending to the right side, with mild vaginal bleeding noted at the time of examination. Vagino-rectal examination revealed free bilateral parametria, with no evidence of rectovaginal or vesicovaginal septal involvement.

Cervical biopsy showed fragments of non-keratinizing squamous cell carcinoma associated with fibrino-leukocytic exudate. No definite stromal invasion was identified on the biopsy specimen. Immunohistochemical analysis demonstrated diffuse p16 positivity and wild-type p53 expression, consistent with an HPV-related squamous cell carcinoma. The Ki-67 expression in approximately 60% of tumor cells.

Preoperative pelvic magnetic resonance imaging (MRI) performed with and without contrast showed a solid cervical lesion measuring 30 x 24 mm, with stromal involvement and extension to the right vaginal fornix. No parametrial invasion was identified.

Preoperative contrast-enhanced total-body computed tomography (CT) and FDG PET/CT showed no evidence of pelvic or para-aortic lymphadenopathy and no distant metastatic disease. FDG uptake was limited to the cervical lesion, with a maximum standardized uptake value of 8.3.

Based on clinical examination and imaging findings, the disease was staged as FIGO 2018 stage IB2 cervical cancer.

According to current international guidelines, radical hysterectomy with pelvic lymph node assessment represents a standard treatment option for patients with FIGO 2018 stage IB2 cervical cancer who are suitable for surgery and have no desire for fertility preservation (Cibula et al., 2023).

Based on current international guidelines and after multidisciplinary discussion, the patient was deemed suitable for primary surgical management. She therefore underwent radical hysterectomy with bilateral adnexectomy and extended pelvic lymphadenectomy.

A total of 41 pelvic lymph nodes were removed and submitted for histopathological examination, including bilateral pelvic, common iliac, and obturator lymph nodes. Pathological ultrastaging was performed on all lymph node specimens according to institutional protocol.

Final histopathological evaluation demonstrated a moderately differentiated (G2), non-keratinizing squamous cell carcinoma of the uterine cervix, HPV-related, with a maximum depth of stromal invasion of 14 mm and diffuse lymphovascular space invasion. Surgical margins and parametrial tissues were free of disease.

Lymph node assessment revealed a single intracapsular micrometastasis in one right pelvic lymph node (1/22), while the remaining 40 lymph nodes were negative for metastatic involvement. No MAC disease was identified. According to the TNM/AJCC and FIGO 2018 classification systems, the final pathological stage was pT1b1 G2 pN1 (MIC), corresponding to FIGO 2018 stage IIIC1.

4. Postoperative course and adjuvant treatment decision

The immediate postoperative course was initially uneventful. Approximately ten days after surgery, the patient developed wound dehiscence associated with purulent discharge from the abdominal incision. Clinical and radiological assessment confirmed an infection limited to the subcutaneous adipose tissue, without involvement of the underlying fascia or peritoneal cavity. The wound status at 76 days after surgery is shown in Fig. 1.

Fig. 1.

Abdominal wound dehiscence with subcutaneous infection, 76 days after radical hysterectomy (22 April 2024). Fascial integrity was preserved.

Wound cultures revealed polymicrobial growth, including methicillin-resistant species. Despite targeted antibiotic therapy and two attempts at secondary closure, wound healing was significantly delayed, likely favored by severe obesity and persistent hyperglycemia. Negative-pressure wound therapy was subsequently initiated, resulting in gradual wound healing over a prolonged period exceeding 100 days.

According to current standards of care, nodal metastasis after radical surgery represents an indication for adjuvant pelvic radiotherapy with concurrent platinum-based chemotherapy. However, the prolonged postoperative complications in this case precluded timely initiation of adjuvant treatment. Given the extended interval from surgery, the absence of macrometastatic disease, and the presence of isolated micrometastasis without additional high-risk features beyond LVSI, late adjuvant therapy was not pursued, and close surveillance was adopted.

5. Follow-up and outcome

During follow-up, the patient underwent serial clinical and imaging evaluations. A contrast-enhanced total-body CT scan performed in December 2024 showed no evidence of locoregional recurrence or distant metastatic disease. An 18F-FDG PET/CT performed in January 2025, confirmed the absence of metabolically active lesions. A subsequent contrast-enhanced total body CT scan in October 2025 again demonstrated no signs of local recurrence, nodal involvement, or distant metastases.

Gynecological follow-up with transvaginal ultrasound in January 2026 revealed a normal postoperative pelvic status, with an intact vaginal cuff, no pelvic masses, and free parametria. Cervicovaginal cytology was negative for intraepithelial lesion or malignancy according to the Bethesda 2014 system, with only mild inflammatory changes reported.

At a follow-up approaching 24 months after primary surgery, the patient remains clinically, radiologically, and metabolically disease-free despite omission of adjuvant chemoradiotherapy.

6. Discussion

The present case describes a patient with early-stage cervical squamous cell carcinoma who underwent primary radical surgery with extended pelvic lymphadenectomy and was ultimately staged as FIGO 2018 IIIC1 due to the presence of a single MIC pelvic lymph node. MIC disease was identified in only one lymph node among a total of 41 removed.

Despite a formal indication for adjuvant chemoradiotherapy based on nodal status, postoperative infectious complications led to a significant delay in wound healing and ultimately precluded the timely administration of adjuvant treatment. At a follow-up approaching 24 months after primary surgery, the patient remains clinically, radiologically, and metabolically disease-free.

The prognostic relevance of lymph node involvement in early-stage cervical cancer is well established for MAC disease, which is consistently associated with an increased risk of recurrence and reduced disease-free and overall survival (Delgado et al., 1989, William et al., 2000). Accordingly, MAC nodal involvement represents a clear indication for adjuvant treatment after radical surgery. Historical survival analyses of node-positive patients treated with radical surgery have demonstrated drastically inferior outcomes when adjuvant therapy is omitted. In particular, 5-year overall survival has been reported as 12.6% in patients receiving no adjuvant treatment compared with 53.7% in those treated with postoperative adjuvant therapy (Cheng et al., 2004). Survival curves demonstrate an early separation between treated and untreated patients, underscoring the critical role of adjuvant therapy in high-risk disease (Cheng et al., 2004). In contrast, the clinical significance of low-volume nodal disease remains less clearly defined.

The introduction of sentinel lymph node biopsy combined with ultrastaging has increased detection of low-volume metastases (Diaz et al., 2011, Margioula-Siarkou et al., 2023). However, available evidence does not consistently demonstrate an independent adverse prognostic impact of low-volume nodal disease, and substantial heterogeneity exists across studies regarding patient selection, pathological assessment, and use of adjuvant therapy (Guani et al., 2020, Dostálek et al., 2023). These observations raise the question of whether tumor burden, rather than mere nodal positivity, should be incorporated into future risk stratification models.

Cervical cancer recurrence tends to occur predominantly within the first two to three years after primary treatment. For this reason, post-treatment surveillance is more intensive during this period, while the risk of recurrence decreases substantially thereafter (Salani et al., 2011).

This single observation cannot challenge current guideline-based recommendations, but illustrates that favorable outcomes may occasionally be observed in individual cases despite omission of adjuvant therapy, highlighting the complexity of prognostic stratification in low-volume nodal disease.

7. Conclusions

This case underscores the persistent uncertainty surrounding the prognostic and therapeutic significance of low-volume lymph node metastases in cervical cancer. Despite increasingly refined surgical and pathological techniques, the biological and clinical relevance of individual risk factors remains incompletely understood.

Further prospective, high-quality studies are needed to move beyond size-based classifications and to better define which patients truly benefit from adjuvant treatment. A more nuanced, biologically driven risk stratification may ultimately allow more personalized and proportionate management of early-stage cervical cancer.

This case reinforces the need to continuously integrate emerging pathological insights into clinical practice, while maintaining full respect for guideline-based standards of care.

Ethics statement

According to institutional policy, ethical approval was not required for a single case report.

CRediT authorship contribution statement

Francesco Pio Toscano: Writing – original draft, Formal analysis, Data curation, Conceptualization. Lucio M.A. Cipullo: Writing – review & editing, Methodology, Investigation. Anna I. Rispoli: Visualization, Supervision. Bruno Curcio: Methodology, Investigation. Maria D’Angelo: Writing – review & editing, Visualization. Raffaella Del Papato: Visualization. Roberta Gallo: Data curation. Sara Mari: Resources. Giuseppe Laurelli: Writing – review & editing, Validation, Supervision.

Funding

No funding was received.

Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.