Re: long-term outcomes of patients with lymph node metastasis treated with radical prostatectomy without adjuvant androgen-deprivation therapy.

Experts’ summary:In a recently published paper in European Urology, Touijer and coworkers noted that pathologic Gleason score, as well as the number of positive nodes, was significantly correlated with prostate cancer (PCa) outcome in one of the largest retrospective series of node-positive patients after radical prostatectomy (RP) without adjuvant therapy (369 consecutive patients). The study showed that for each year without biochemical recurrence (BCR), the probability of BCR-free survival increases annually to approximately 80% after 5 yr. The Gleason score and the number of positive nodes were important predictors of metastasis-free and BCR-free survival on multivariate analysis. The main message of the paper by Toujier and coworkers is that node-positive patients can have a good prognosis (in terms of survival) even without adjuvant therapy; however, the authors stressed that node-positive patients are not all at the same risk of cancer-specific death. Even if some limitations in the study design must be noted—for example, the lymph node density was not considered, the Gleason score can vary significantly throughout such a long study period, and there was a single-center source of data—the authors confirm a good outcome for node-positive patients with low metastatic tumor burdens.Experts’ comments:The concept that patients with low-volume metastasis have significantly higher survival rates than patients with a high-volume metastatic pattern is quite instinctive. Similar to Touijer et al., we recently reported on our series of 98 node-positive patients and found that patients with one to three positive lymph nodes had higher cancer-specific and overall survival than patients with more than three positive nodes. We stratified our patients into three risk-group categories according to number of positive nodes and Gleason score to better predict oncologic outcomes and found considerable differences in terms of cancer-specific and overall survival [1]. The idea that a proportion of node-positive patients with low tumor burden treated with RP plus extended pelvic lymph node dissection (PLND) might have optimal survival even without adjuvant or salvage therapy is attractive and could support an aggressive approach to treatment in such patients. This idea leads us to the following question: Is metastatic PCa a single risk category to be treated with an identical, mild, and remissive approach? Unlike other malignancies [2], the therapeutic role of regional lymph node dissection in PCa is still uncertain, and the metastatic pattern of PCa cells is not completely understood. However, tumor dissemination in bone vessels or lymphatic vessels can follow different patterns both biologically and chronologically [3]. In the initial phase of the metastatic pattern, some patients might have tumor dissemination only in the pelvic nodes without bone dissemination; thus, in a very carefully selected group of these patients, an extended PLND and RP could be sufficient to treat the disease. Indeed, what is the sense of performing RP to treat high-risk PCa while leaving PCa cells behind in the pelvic nodes? In contrast, if metastatic cells are already present in the bones of node-positive patients at the time of primary treatment and the spread involves lymphatics and bones simultaneously, these cells will remain quiescent for many years. For now, a complete lymphadenectomy plus RP or complete pelvic irradiation administered in the setting of multimodal therapy is the only option available that could help to reduce the tumor volume and help render the PCa a chronic disease with slowed progression. Unfortunately, the current radiologic and molecular diagnostic armamentarium is not adequately accurate to rule out bone metastases, so prompt therapy must be given to patients at high risk of micrometastasis. We hope that new promising radiotracers such as 18F-fluorocyclobutyl-1-carboxylic acid positron emission tomography/computed tomography might become helpful options in the early identification of bone or lymphatic involvement to better address the optimal therapeutic approach in the future [4]. In conclusion, we completely agree with Touijer and coworkers that not all patients with node-positive PCa have the same risk of cancer-specific death and that stratification can help identify those patients with few lymph node metastases who might expect a better prognosis