Distant Metastasis Disease-free Survival Research Articles

Is Substantial Lymphovascular Space Invasion Prognostic in Patients With Pathologically Lymph Node-Negative Endometrial Cancer?

Lymphovascular space invasion (LVSI) predicts for higher rates of recurrence and increased mortality in endometrial cancer. Using 3-tier LVSI scoring, a PORTEC-1 and -2 trials analysis demonstrated that substantial LVSI was associated with worse locoregional (LR-DFS) and distant metastasis disease-free survival (DM-DFS), and these patients possibly benefited from external beam radiation therapy (EBRT). Furthermore, LVSI is a predictor for lymph node (LN) involvement, but the significance of substantial LVSI is unknown in patients with a pathologically negative LN assessment. We aimed to evaluate clinical outcomes of these patients in relation to the 3-tier LVSI scoring system. We performed a single-institutional retrospective review of patients with stage I endometrioid-type endometrial cancer who underwent surgical staging with pathologically negative LN evaluation from 2017 to 2019 with 3-tier LVSI scoring (none, focal, or substantial). Clinical outcomes (LR-DFS, DM-DFS, and overall survival) were analyzed using the Kaplan-Meier method. A total of 335 patients with pathologically LN-negative stage I endometrioid-type endometrial carcinoma were identified. Substantial LVSI was present in 17.6% of patients; 39.7% of patients received adjuvant vaginal brachytherapy and 6.9% of patients received EBRT. Adjuvant radiation treatment varied by LVSI status. In patients with focal LVSI, 81.0% received vaginal brachytherapy. Among patients with substantial LVSI, 57.9% received vaginal brachytherapy alone, and 31.6% of patients received EBRT. The 2-year LR-DFS rates were 92.5%, 98.0%, and 91.4% for no LVSI, focal LVSI, and substantial LVSI, respectively. The 2-year DM-DFS rates were 95.5%, 93.3%, and 93.8% for no LVSI, focal LVSI, and substantial LVSI, respectively. In our institutional study, patients with pathologically LN-negative stage I endometrial cancer with substantial LVSI had similar rates of LR-DFS and DM-DFS compared with patients with none or focal LVSI. These findings highlight the need for multi-institutional studies to validate the prognostic value of substantial LVSI in this patient population.

Is Substantial Lymphovascular Space Invasion Prognostic for Clinical Outcomes in Type II Endometrial Cancer?

AimsSubstantial lymphovascular space invasion (LVSI) compared with none or focal LVSI is predictive of lymph node involvement and worse clinical outcomes in endometrioid-type endometrial carcinoma. We aimed to quantify the incidence of substantial LVSI in type II (clear cell and serous) endometrial cancer and correlate the extent of LVSI with clinical outcomes. Materials and methodsA retrospective review was conducted on type II endometrial cancer patients who underwent surgical management from July 2017 to December 2019 using the three-tier LVSI scoring system. Binary logistic regression and Cox regression were used to analyse predictors of lymph node involvement or survival outcomes, respectively. The Kaplan–Meier method and Log-rank test were used to analyse differences in locoregional disease-free survival (LR-DFS), distant metastasis disease-free survival (DM-DFS) and overall survival between patients with substantial versus none/focal LVSI. ResultsIn 79 patients with type II endometrial carcinoma, no LVSI, focal LVSI and substantial LVSI was present in 48.1%, 15.2% and 36.7% of patients, respectively. Lymph nodes were involved in 0.0% with no LVSI, 20.0% with focal LVSI and 60.0% with substantial LVSI (P < 0.001). The median follow-up was 22.2 months. In patients with none/focal versus substantial LVSI, the 2-year LR-DFS and DM-DFS rates were 91.5% versus 71.4% (P = 0.01) and 90.2% versus 63.8% (P = 0.005), respectively. On univariate analysis, myometrial invasion ≥50%, tumour size ≥3.6 cm, substantial versus none/focal LVSI, lymph node involvement and omission of adjuvant radiotherapy were significant predictors for worse LR-DFS and DM-DFS (P < 0.05). DiscussionSubstantial LVSI has a high incidence in type II pathology at our institution and predicts for lymph node involvement and worse clinical outcomes.

Opportunity lost and found: Any easy way to improve outcomes for prostate cancer patients in the postoperative setting?

Evidence-based medicine is a paradigm shift and is a key component in the provision of high-quality care. The highest quality evidence is clinical practice guidelines based on systematic reviews of the randomized controlled trial (RCT) literature. There are many challenges to successfully complete RCTs and it is problematic to synthesize recommendations when the RCTs have conflicting results. However, in the case of the utility of adjuvant postoperative radiotherapy (ART), this is not the case. There are three RCTs showing improvements in local and biochemical control;1–3 the study with the longest follow-up (SWOG 8794) also demonstrates improvements in distant metastatic disease-free survival and overall survival.2 Cancer Care Ontario (CCO) published a systematic review of the literature and clinical practice guideline on the topic showing that all subgroups benefitted in biochemical control and overall survival from ART (and those with seminal vesicle involvement seemed to benefit more not less).4 It is very interesting to see how this evidence is applied in the pragmatic setting. In this issue of CUAJ, Tyldesley and colleagues have published a population-based analysis of postoperative radiotherapy in British Columbia from 2007 to 2009.5 Many interesting facts are reported. Over the 3-year observation period, 9223 patients were identified from the tumour registry and linked to centralized radiotherapy records. Of these patients, initial therapy was radical prostatectomy in 24%. Postoperatively, 47% had one or more high-risk features (positive surgical margin: 36%; extracapsular spread: 22%; seminal vesicle involvement: 4%).5 Of the 47% with one or more high-risk features, 23% with any adverse features were seen by a radiation oncologist within 6 months of surgery. Only 10% of these patients received adjuvant ART (i.e., 2% of patients with any high-risk features). Of equal interest, 40% of those with adverse features who were seen were advised against ART. Why are the rates of referral (23%) and recommendation (60%) and use of ART (2%) so low for these patients? The first argument is a lack of knowledge. The EORTC and SWOG studies were published in 2005 and 2006, respectively (and all were presented in abstract before the observation period). Despite this, we know that evidence takes a while to diffuse into practice, particularly community practice. How long is too long when we have a treatment with a solid evidence base that improves not just biochemical, but distant metastatic disease and overall survival rates? Is there anything we could have done differently to accelerate this knowledge dissemination? The second argument is that the treatment is too toxic. It is easy to attribute really bad side effects (such as severe hemorrhagic cystitis) to all patients who might get radiation. However, when prospectively collected, the data demonstrate that the risk of serious RT toxicity was low. In the Wiegel trial, 1% and 0% of patients had grade 3 bladder and bowel problems.3 This is despite patients receiving 2-dimensional RT; RT has improved greatly in target localization with image-guided techniques and my experience is that modern RT has even fewer side effects. It is true that patients would require at least 30 visits to a cancer centre for consult, planning and treatment and for some patients this is costly and inconvenient. Much progress has been made in shortening the course of primary external radiation from 34 to 49 treatments to a few as 5 treatments;6–8 work from our group and Kruser and colleagues’ has applied these same techniques in the postoperative setting to improve the convenience without increasing the toxicity.9 The final argument is that early salvage postoperative RT is as good as immediate ART. Non-randomized data argue against this.10–12 However, this question (and the question of the optimal duration of adjuvant androgen deprivation therapy) is currently being tested in the intergroup RCT RADICALS which is open in more than 20 centres across Canada. Patients with any high-risk features should be considered for this trial. In short, ART is being underutilized. This is a lost opportunity not only for our patients, but also the health care system. There are now 6 systemic therapies which improve overall survival in the castrate-resistant prostate cancer setting, but none have improved median survival more than 5 months. A course of each treatment costs between $20 000 and $118 000 on top of the $11 000 to $32 000 of hormone therapy. In comparison, a course of ART costs about $4000 and improves median survival by 23 months. At 10 years, it offers more survival benefit than SPCG4 documented for radical prostatectomy over watchful waiting (8% vs. 5%).2,13 We have a tremendous opportunity to make a meaningful difference in the lives of our patients and the healthcare system – we just need to listen to the evidence and act accordingly.

Postoperative radiotherapy for primary mucosal melanoma of the head and neck

Primary head and neck mucosal melanoma (HNMM) has a poor prognosis with a low local control rate and frequent distant metastases. The objective of the current study was to determine the impact of postoperative radiotherapy on local control and survival. One hundred forty-two patients with primary HNMM treated between 1979 and 1997 were reviewed. Of these, 69 patients with confirmed primary mucosal melanoma, absence of metastatic disease, and definitive management by surgery with or without postoperative radiotherapy and follow-up at the Institut Gustave-Roussy (Villejuif) were selected. The site of primary HNMM was sinonasal in 46 patients, oral in 19 patients, and pharyngolaryngeal in 4 patients. Twenty-two patients (32%) had a locally advanced tumor (T3-T4) and 17 patients had regional lymph node metastases after pathologic examination (pN > 0). Thirty patients underwent surgery alone and 39 received postoperative radiotherapy. Patients with locally advanced tumors had received postoperative radiotherapy more frequently than those with small tumors (P = 0.02). Thirty-seven patients (54%) experienced local disease recurrence and 47 patients (68%) developed distant metastasis. The overall survival rates were 47% at 2 years and 20% at 5 years. In the Cox multivariate analysis, patients with early T-classification tumors who received postoperative radiotherapy had a better local disease-free survival (P = 0.004 and P = 0.05, respectively) compared with patients with late T-classification tumors who did not receive postoperative radiotherapy. Patients with advanced T-classification and pN > 0 stage had a shorter distant metastasis disease-free survival compared with patients with early T-classification and pN < 0 stage. Patients with advanced T-classification tumors had a shorter overall survival compared with patients with early T-classification tumors (P = 0.003). The prognosis of patients with HNMM was poor. Patients had a high rate of distant metastasis and a low rate of local control. The current study suggested that postoperative radiotherapy increased local control even for patients with small tumors.

Postoperative adjuvant chemotherapy and radiotherapy for stage II and III non-small cell lung cancer (NSCLC)

The role of postoperative adjuvant chemo-radiotherapy in the treatment of patients with non-small cell lung cancer (NSCLC) remains unclear. This study was undertaken to evaluate the survival outcomes, relapse patterns, prognostic factors and complications of postoperative adjuvant MVP chemotherapy and radiotherapy. The study involved some 96 patients who had undergone curative resection of stage II and III NSCLC between 1991 and 1996. Among these, 94 patients who completed their adjuvant treatment were analyzed. Surgery consisted of pneumonectomy (33%), single lobectomy (54%) or bilobectomy (13%). Within 4 weeks of curative resection, two cycles of MVP chemotherapy (mitomycinC 8 mg/m 2, vinblastine 8 mg/m 2, cisplatin 60 mg/m 2) were started at 4 weeks intervals. Conventionally fractionated radiotherapy was given 3 weeks after chemotherapy to a total dose of 50 Gy in completely resected patients and 55–60 Gy in patients with positive resection margins. The TNM classification of the AJCC, as revised in 1997, was used for pathologic staging. The number of patients at AJCC stages IIa, IIb, IIIa, and IIIb were four, 40, 45, and five, respectively. A pathologically positive bronchial resection margin was found in nine patients. At the time of analysis, death was recorded in 29 patients (31%), though five had died without evidence of lung cancer. Overall 2, 3, and 5-year-survival rates for all patients were 74.2, 70.2, and 65%, respectively, and locoregional disease-free survival (LRDFS) rates were 88.6, 83.7, 74.3%, at 2, 3, and 5-years, distant metastasis disease-free survival (DMDFS) rates were 67.7, 65.0, and 63.6%, respectively. In the multivariate model, a primary tumor size of more than 5 cm and the level of pathologically positive nodes were found to be associated with poor overall survival, LRDFS and DMDFS. Although positive bronchial resection margin affected overall survival, LRDFS and DMDFS were unaffected. With respect to the first site of relapse, distant metastasis occurred more frequently ( N=33, 35%) than locoregional recurrence ( N=15, 16%). Grade 3 esophagitis in two patients and weight loss of more than 10% in five patients were observed during adjuvant treatment. Grade 4 pulmonary toxicity was observed in one patient after radiotherapy and this patient ultimately died 5 months after treatment. The postoperative adjuvant MVP chemotherapy and radiotherapy regimen showed relatively low locoregional recurrence and distant metastasis rates and good survival with acceptable toxicity. A prospective randomized trial, which compares this regimen to surgery alone or postoperative adjuvant radiotherapy is needed.