Prostate cancer commonly occurs in the urinary system of males. It has the highest incidence rate among different types of cancer in males in the US and Europe (1–3). Prostate cancer has no specific symptoms. Although awareness among people and screening for prostate-specific antigen (PSA) by healthcare institutions has increased in China, the rate of incidence of new prostate cancer cases has increased significantly in recent years. Thus, in the Chinese population, prostate cancer has become a serious health concern (4, 5). According to the Global Cancer Data Center study, the five-year survival rate of patients with early-stage prostate cancer is 100%, whereas, the five-year survival rate of patients with late-stage prostate cancer is only 28% (6). As the disease progresses, patients often develop lower urinary tract symptoms (LUTS), including straining to urinate, dribbling, frequency, urgency, difficulty urinating, increased nocturia, hematuria, etc. The most common methods used to diagnose prostate cancer in clinical settings include serum prostate-specific antigen (PSA) assessment, rectal finger examination (RFE) and transrectal ultrasound (TRUS) examination, pelvic MRI, CT scanning, and isotope bone scanning. However, the gold standard for diagnosis is prostate puncture biopsy (7, 8). The combination of serum PSA levels, clinical staging, and Gleason score of puncture pathology can be used to classify clinically limited prostate cancer into low-risk, intermediate-risk, and high-risk groups. This classification system can help decide the treatment regimen for patients with prostate cancer.

The best treatment modality for prostate cancer patients is determined by assessing their Gleason score, serum PSA levels, clinical stage, life expectancy, and self-reported general condition, along with the presence of distant metastases (9). Commonly used clinical treatments include close monitoring and active surveillance, resective prostatectomy, external radiation therapy, proton therapy, cryoablation, high-energy focused ultrasound therapy, and endocrine therapy (10). Prostatectomy is the most commonly used method for treating prostate cancer. It is the most effective treatment strategy for limited prostate cancer and some types of high-risk prostate cancer (11). After undergoing excisional prostatectomy, patients have a five-year disease-specific survival rate of >95% (12). Laparoscopic prostatectomy is the gold standard for treating limited prostate cancer. However, even after undergoing extremely successful intraoperative treatment, 10–40% of patients present with PSM pathology after prostate cancer resection (13).

PSM refers to the presence of cancer cells on the ink-stained surface of the prostatectomy specimen. Surgical PSM can be of two types. In the first type, the cancerous tissue invades outside the envelope, leaving cancerous tissue outside the prostate on the ink-stained margins, i.e., true positive. In the second type, the cancerous tissue is confined to the envelope. In such a case, if the periprostatic fascia and envelope are cut and accidentally enter the prostate gland, a portion of the fascia and envelope disappears from the specimen, leaving cancerous tissue inside the prostate on the ink-stained margins, i.e., false positive (14). Men with post-prostate cancer resection specimens suggestive of PSM have a higher chance of experiencing clinical biochemical recurrence (15). A large multi-institutional study showed a 3.7-fold association between PSM and the risk of biochemical recurrence in nearly 6,000 men treated with prostate cancer resection. Spahn et al. analyzed more than 7,000 patients who underwent prostate cancer resection. They constructed a multivariate model and included factors such as age, Gleason score, PSA, extraperitoneal invasion, and seminal vesicle invasion and found that PSM was independently associated with biochemical recurrence (HR 2.3, 95% CI 2.1–2.6, p < 0.001) (16). Therefore, achieving negative surgical margins (NSM) is crucial to increase the chances of survival among prostate cancer patients. However, the proportion of patients with locally progressive intermediate-risk and high-risk prostate cancer undergoing prostatectomy has recently increased considerably (17), which in turn has significantly increased the risk of postoperative PSM. Several studies have shown that postoperative PSM in prostate cancer is correlated with post-penetration Gleason score, PSA level, tumor infiltration in seminal vesicles, clinical stage of the tumor, size (volume) of the prostate, proficiency of the surgeon, the age and body mass index of the patient, and biopsy nerve infiltration (18–21).

Although many studies have investigated PSM in prostate cancer, most researchers conducted cross-sectional surveys in prostate cancer patients. These researches have shown that serum PSA, perineural invasion, puncture biopsy Gleason score, and percentage of positive puncture stitches were independent risk factors for PSM. Moreover, lymph node metastasis and nutritional status were found to be the main risk factors for the five-year survival of patients with prostate cancer. This scoring system has moderate efficacy in predicting the risk of PSM after prostate cancer resection.

Prostate cancer is a malignant tumor that occurs in prostate tissue. It results from the abnormal and disordered growth of prostate acinar cells (22). The disease generally has no specific symptoms in the early stage of onset. As the tumor grows, patients start showing symptoms such as frequent urination, urgent urination, slow urination, laborious urination, and even urine retention or urinary incontinence, which severely affects their quality of life (23, 24). Thus, patients with prostate cancer need to be treated with suitable methods for the best possible outcome. Clinicians are now paying greater attention to the quality of life of elderly patients with prostate cancer.

The most important indicator of complete tumor resection is whether the cut-edge status of the specimen is positive after prostate cancer resection. PSM is treated as a high-risk factor for disease progression after surgery, and urologists have investigated it for a long time. The presence of tumor cells at the cut edge of the specimen, based on a postoperative pathology report, indicates PSM, suggesting incomplete removal of the tumor. In a multicenter study, data were collected on the cut-edge status of 2,385 patients who underwent prostate cancer resection. Based on the National Comprehensive Cancer Network (NCCN) risk classification, the researchers found that the PSM rate was 19.1% (102/534) in the low-risk group, 26.0% (317/1218) in the moderate-risk group, 39.5% (153/387) in the high-risk group, and 81.8% (9/11) in the very high-risk disease group of patients (25). The results of this study were similar to the findings of the abovementioned study. Our findings also suggested that PSM after prostate cancer resection is strongly associated with postoperative biochemical recurrence and disease progression. A research group conducted a meta-analysis and found that PSM is associated with a high risk of biochemical recurrence after prostate cancer resection and may be an independent prognostic factor for the prognosis of patients with prostate cancer (26). Similarly, Jo et al. showed that after undergoing robot-assisted prostatectomy, PSM is a strong predictor of biochemical recurrence (27, 28). In the clinical setting, biochemical recurrence often indicates further disease progression, with the possibility of local recurrence or distant metastases, which can seriously threaten patient survival. Therefore, identifying the risk factors associated with PSM and establishing a scoring system for determining the risk of PSM after prostate cancer resection might provide a reference tool for preoperative prostate patients to predict the status of pathological margins after prostate cancer resection. Accurate predictions may help avoid PSM and improve patient prognosis.

In this study, we showed that PSM after prostate cancer surgery was associated with the post-penetration Gleason score, PSA level, seminal vesicle tumor infiltration, clinical stage of the tumor, size of the prostate volume, proficiency of the surgeon, the age and body mass index of the patient, biopsy nerve infiltration, and number of positive preoperative biopsy punctures (29, 30). Although these factors cannot be controlled, they suggest that early detection and treatment of prostate cancer is important, especially via PSA detection (8, 31–33). Therefore, for patients with prostate cancer receiving treatments via different methods, corresponding measures to improve the survival time need to be determined for better recovery of patients after surgery or follow-up radiotherapy and chemotherapy (34, 35). Illness-related behavior depends on the attitude and perspective of patients toward the disease; the mood, behavior, and level of cognition all influence the quality of life and well-being of patients (36, 37).The results of the binary logistic regression analysis showed that preoperative serum prostate-specific antigen, percentage of positive preoperative puncture stitches, puncture Gleason score, and preoperative puncture biopsy nerve invasion were independent risk factors for PSM. Tuliao et al. also found that the number of positive preoperative biopsy needles ≥3 (OR = 2.52, P = 0.043) was a predictor of postoperative PSM in a study on robot-assisted prostate cancer resection (38). Yang et al. retrospectively analyzed 296 patients who were diagnosed with rectal ultrasound prostate biopsy and treated with laparoscopic prostatectomy (OR = 4.403, 95% CI = 1.8). They found that the number of positive preoperative biopsy stitches (OR = 4.403, 95% CI = 1.878–10.325, P = 0.001) was an independent predictor of PSM (39). Heidenreich et al. performed a multifactorial analysis and found that a preoperative positive biopsy needle count of <50% was a significant predictor of pathologically negative margins after surgery for a clinically limited prostate cancer factor (40). In this study, we found that the percentage of patients with PSM was high (63.2%; 48/76) when the percentage of positive stitches was ≥50%. This makes the percentage of positive puncture stitches as the number of puncture stitches varies between institutions. In this study, the results of the univariate analysis showed that preoperative clinical staging was significantly different based on the margin status. The proportion of PSM patients with clinical staging ≥T2c was 64.5% (49/76), which was significantly higher than the proportion of PSM patients with clinical staging ≤T2b. Some researchers have found that clinical staging acts as an independent risk factor for PSM (41), but binary logistic regression analysis in this study showed that staging after clinical is not an independent risk factor for PSM. Koizumi et al. evaluated the clinical outcomes of 450 patients who underwent resective prostatectomy and conducted a multifactorial analysis. Their results showed that the mode of surgery was not an independent risk factor for PSM (42), which matches the results of this study.

In this study, a prospective case-control approach was used with strong causal inference. Based on the results of logistic regression, a quality-of-life prediction model with a good predictive effect on the survival time of patients can be established (43–46). Paying clinical attention to the observation and application of the abovementioned indicators can help predict the survival time of prostate cancer patients under treatment. Implementing relevant interventions early can be more effective in reducing the effect of risk factors; thus, improving the quality of life of patients (47–49). Evaluation of the clinical nutritional status, lymph node metastasis, and other indicators is suitable as additional costs and burdens are not imposed on patients for testing interventions (50, 51). Tools to evaluate disease-related behavior and family engagement support are also effective and suitable; moreover, they do not increase the burden on medical staff (52).

In this study, we identified the risk factors for PSM after prostate cancer resection. The area under the ROC curve was smaller than the area under the ROC curve of the scoring system if the PSM after prostate cancer resection was predicted by serum PSA, percentage of positive puncture stitches, the Gleason score, or perineural invasion alone. After determining the OR of each risk factor by binary multi-factor logistic regression analysis, scores were assigned, ROC curves were plotted, cut-off values were assessed, and finally, the risk prediction scoring system for PSM was established. The scoring system included the following risk factors: presence of perineural invasion on preoperative biopsy (yes = 2 points and no = 1 point), serum PSA (<10 ng/mL = 1 point, 10–20 ng/mL = 2 points, and >20 ng/mL = 4 points), Gleason score (<6 = 1 point, 7 = 2 points, and ≥8 = 4 points), and percentage of positive puncture stitches (<25% = 1 point, 25–49% = 2 points, and ≥ 50% = 4). Based on these parameters, we established a scoring system (minimum and maximum scores: 4 and 14, respectively). The clinical parameters of this scoring system were easily accessible, and the effectiveness of the scoring system was expressed by the area under the ROC curve. When the hazard score was 5.976, the sensitivity and specificity were 66.7% and 80.9%; when the hazard score was 6.144, the sensitivity and specificity were 66.3% and 84.4%; when the hazard score was 6.298, the sensitivity and specificity were 59.5% and 86.6%. For the best sensitivity and specificity, the hazard score cut-off value of this scoring system was found to be 6. We used a cut-off value of 6 to classify the patients into a “low-risk” group (4–5 points) with 36.8% PSM and a “high-risk” group (6–14 points) with 48.7% PSM. The differences between the risk groups were significant. While applying these factors as predictors of the scoring system, the combination of these factors showed that this scoring system is useful for the preoperative assessment of the clinical condition of patients.

This study had some limitations, for example, the operators were different, and postoperative pathology specimens were analyzed by different pathologists. Also, some indicators, such as body mass index, pathological staging, etc., were not included in the study. The sample size was too small to establish a scoring system. Thus, more patients need to be included, and a multicenter study needs to be conducted to validate our findings. As our study was descriptive, statistical analyses could not be performed to test any hypothesis.

To summarize, we identified several risk factors for PSM after prostate cancer resection. We found that serum PSA, percentage of positive puncture stitches, and the presence of perineural invasion by puncture are independent risk factors for PSM. A scoring system established based on these three factors showed moderate efficacy in predicting the risk of PSM after prostate cancer resection. For prostate cancer patients with a risk score below 6, the nerve can be preserved intraoperatively, whereas for those with a risk score of 6 and above, extended resection may be needed.