The role of PN in the treatment of cT1 RCC has been well studied. While Chen et al. showed that the rate of cT1 upstaged to pT3a ranged from 3.2–31%, median 5.5% . Moreover, upstaged cT1/pT3a RCC was associated with poor recurrence-free survival, overall survival, and cancer-specific survival in the most of the reports . It has been showed that several factors would affect the prognostic of pT3a RCC, such as tumor size, invasion site, tumor grade and pathology type. Tumor size over 7 cm is an important poor factor for predicting the outcome of patients with pT3a RCC with fat invasion [8, 9]. Furthermore, there is a trend of worse outcomes with tumor size increases from 0-4cm to 4-7cm and over 7 cm in pT3a RCC . We previously showed that the PFI and SFI has similar prognosis, and single fat invasion site invasion has better survival than multiple sites invasion in pT3aN0M0 RCC . There are also some studies showed that tumor grade and pathology type could affect the survival of pT3a RCC [12, 13]. These studies suggested tumor size, invasion site, tumor grade and pathology type were the prognostic factors of pT3a RCC.
The survival benefit of surgical type (PN/RN) in pT3a RCC patients is controversial. Great majority of studies showed that PN has similar survival outcomes with RN in pT3a RCC. There is very limited evidence regarding whether RN or PN is better in pT3a RCC . Oh et.al. reported that PN provides similar recurrence-free survival outcomes compared with RN in patients with 0-4cm pT3a RCC . Lee et al. showed no significant difference in survival of the PN group when compared to the RN group in tumor size < 7 cm pT3aRCC . However, Ziegelmueller et al. showed that PN in pT3a RCC leads to better survival outcomes compared to RN in tumor size < 7 cm . While Shah et al. reported PN was associated with shorter recurrent-free survival compared to RN in cT1/pT3a upstaged patients (49 PN vs 91 RN), in which the positive margin rate was approximately 15% (7/49), and more than half (4/7) of positive margin patients recurred in PN . Although the survival benefit is inconsistent, most of the studies showed that PN patients had a higher postoperative eGFR than RN patients . Actually, there are some shortcomings in previous studies, such as small sample size, short follow-up time, lacking invasion site and tumor size information, and including Nx/N1 patients. Moreover, single or inadequate analysis model is also an important factor.
To our knowledge, this observational study contains the largest cohort of pT3aN0M0 RCC to analyze the survival of PN (200 cases) and RN (1077 cases). And factors including age, gender, tumor size invasion site, grade, and pathology type, which may affect survival, were all analyzed. As it is rare to perform PN in pT3a RCC over 7 cm, thus we focus on pT3aN0M0 RCC less than 7 cm, comparing the survival differences between PN and RN. Unadjusted data showed that the characteristics of pT3aN0M0 patients are significantly different in tumor size, invasion site, tumor grade, pathology type and surgery type, therefore it is necessary to balance the bias by using analytic models. Previous studies did not balance the bias or just used the match model, which might result in unreliable conclusions. Propensity score analyses were more reliable to control imbalances in individual risk factors .
There are inconsistent conclusions of PN and RN for T3a RCC from previous studies, and majority of these studies showed similar survival outcomes between PN and RN in T3aN0M0 RCC. Our data showed that PN is associated with better survival compared to RN in 0-4cm pT3aN0M0 RCC. It is clear that the OS/CSS of PN is comparable to RN in cT1 RCC from the prospective and retrospective clinical studies, and PN decreases chronic kidney disease [21–23]. The survival benefit of PN in 0-4cm pT3aN0M0 RCC may be explained by Hamilton, Z.A., which showed that most recurrences were distant with a recurrence rate of 92.5% (99/107), and loco-regional recurrence was only 11.2% (12/107) in upstaged pT3a RCC, which was even lower than loco-regional recurrence of 17.8% (30/169) in non-upstaged cT1-2 RCC . Furthermore, Patel et al. reported that in pathologically upstaged pT3a RCC, PN did not adversely affect risk of recurrence and provided functional benefit .Although, Shah et al. reported that cT1/pT3a upstaged patients (49 PN/91 RN), the positive margin rate was approximately 15% (7/49) in PN, and more than half (4/7) of positive margin patients recurred . The positive margin of PN significantly increased in cT1/pT3a RCC, compared with cT1/pT1 . While, positive margin was not associated with local recurrence of pT3a RCC . As distant recurrence is the major risk of locally advanced T3a RCC patients, therefore, local positive margin may not be a key prognostic factor in this cohort patients. Single, rather than multiple sites invasion, is the major invasion characteristic of 0-4cm pT3aN0M0 RCC, which is possible to be completely removed by PN surgery. Thus, the effect of the local disease control may be similar in 0-4cm pT3aN0M0 RCC patients between PN and RN. In this study, the results have further been confirmed by propensity score (–adjusted, –stratified, –weighted, and –matched) analyses, which may attenuate the possibility of bias. The cohort of 4-7cm pT3aN0M0 RCC, PN has similar survival outcomes compared with RN, which indicated that tumor size is still the key prognostic factor for pT3aN0M0 RCC.
PN is a technically demanding surgery, especially for patients with tumors > 7 cm, Fuhrman grade III-IV, and pT3a. RN is the first choice for T3a RCC. While PN can preserve additional renal function and lead less cardiovascular disorders, which may let pT3aN0M0 RCC patients have better tolerance to adjuvant therapy with targeted drug, and it is benefic for longer disease-free survival of advanced RCC patients . Therefore, PN is not a contraindication for T3a RCC patients. Especially for T3a RCC patients with smaller size 0-4cm, whom even can benefit from PN.
Although this is the largest cohort used to assess the survival benefit of PN in pT3aN0M0 RCC, it has several limitations. Limitations of the present study include the retrospective nature of the analysis. Selection bias is another important limitation which is intrinsic to the retrospective design of the study. Though we analyzed several prognostic factors of pT3aN0M0 RCC including tumor size, grade, pathology type, and invasion site for the first time, some prognostic factors including positive margin, perioperative complication, renal function, metastasis and adjuvant therapy were not analyzed here. Propensity score-based approaches are sufficient for minimizing the impact of observed confounders, such methodology does not address unobserved confounders (ie, unmeasured patient selection factors for PN/RN that are also associated with survival such as hypertension and diabetes). Furthermore, there is no central pathology review to reconfirm pathological characteristics, as this was a national data set study, Lastly, follow-up was relatively short and endpoint events only occurred in a small part of patients.