Abstract:Objective To systematically evaluate and compare the clinical efficacy and prognosis of medical conservative therapy versus surgical treatment for nodular pulmonary cryptococcosis in immunocompetent patients. Methods A retrospective study included 59 patients with solitary nodular pulmonary cryptococcosis who were diagnosed and treated at Jiangsu Provincial Hospital of Chinese Medicine from September 2015 to August 2023. The general data， serial chest imaging features and changes of serum capsular polysaccharide antigen（CrAg） were collected. The patients were divided into two groups according to the treatments. For the medical treatment group（27 cases，treated with oral fluconazole 400 mg/d），follow-up 1 and follow-up 2 were at 6 months of treatment and 6 months after discontinuation，respectively；correspondingly，for the surgical treatment group（32 cases，undergoing wedge resection to remove pulmonary lesions），follow-up 1 and follow-up 2 were at 6 months and 1 year post-surgery， respectively，to comprehensively evaluate their short - term and long - term treatment responses. Continuous variables from single-group repeated measurements were analyzed using the repeated measures ANOVA，and categorical variables from two-group repeated measurements were analyzed using generalized estimating equations. Results There were no statistically significant difference between the two groups of patients in terms of gender，lesion location，maximum lesion diameter， and pre - treatment serum CrAg positivity rate（P>0.05）.（1）Medicine treatment group：imaging evaluation at follow-up 1，follow-up 2 showed that only 4 cases（14. 8%）achieved complete radiological remission. The repeated measures ANOVA test showed that there was a statistically significant overall difference in lesion diameters at baseline［（1.85±0.76）cm］，follow-up 1［（1.27±0. 80）cm］，and follow-up 2［（1.26±0.77）cm］（F= 17.278，P<0.01）， with diameters at both follow-up 1 and follow-up 2 being lower than at baseline（P<0.01）. The positive rate of serum CrAg did not change significantly across the three time points（ P>0.05）.（2）Surgical treatment group： during postoperative follow- up，no new nodule appeared at the surgical site or other lung fields；postoperative serum CrAg gradually turned negative，with 93.75%（30/32）at follow-up 2.（3）Inter-group comparison：the positive rate of serum CrAg in the surgical treatment group was significantly lower than that in the medical treatment group at both follow-up 1（15.63% vs 74.07%，χ2=20.488，P<0.01）and follow-up 2（6.25% vs 70.37%，χ2=26.264，P<0.01）. Conclusion For immunocompetent patients with nodular pulmonary cryptococcosis，a 6-month course of medical antifungal therapy can partially reduce the lesions，but yields low rates of complete radiological resolution and seroconversion of CrAg. In contrast，surgical intervention can achieve complete lesion eradication，with seroconversion of CrAg in most cases within one year and no recurrence，indicating a more thorough disease control effect.