Tumor growth pattern as predictor of colorectal liver metastasis recurrence

Background

Surgical resection is the gold standard therapy for the treatment of colorectal liver metastases (CRM). The aim of this study was to investigate the impact of tumor growth patterns on disease recurrence.

Methods

We enrolled 91 patients who underwent CRM resection. Pathological specimens were prospectively evaluated, with particular attention given to tumor growth patterns (infiltrative vs pushing).

Results

Tumor recurrence was observed in 65 patients (71.4%). According to multivariate analysis, 3 or more lesions (P = .05) and the infiltrative tumor margin type (P = .05) were unique independent risk factors for recurrence. Patients with infiltrative margins had a 5-year disease-free survival rate significantly inferior to patients with pushing margins (20.2% vs 40.5%, P = .05).

Conclusions

CRM patients with pushing margins presented superior disease-free survival rates compared with patients with infiltrative margins. Thus, the adoption of the margin pattern can represent a tool for improved selection of patients for adjuvant treatment.     

Laparoscopic Radical Cystectomy with Orthotopic Ileal Neobladder for Bladder Cancer: Oncologic Results of 171 Cases With a Median 3-Year Follow-up

Background

Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard treatment for muscle-invasive and high-risk non–muscle-invasive bladder cancer (BCa). Large series with long-term oncologic data after laparoscopic RC (LRC) are rare.

Objective

To report oncologic outcomes of LRC for 171 cases with a median 3-yr follow-up.

Design, setting, and participants

From December 2002 to June 2009, 171 consecutive patients with BCa who underwent LRC with orthotopic ileal neobladder (OIN) at our institution were enrolled in this retrospective study.

Intervention

All patients underwent LRC OIN. Adjuvant chemotherapy was administered to patients with non–organ-confined disease or positive lymph nodes.

Measurements

The demographic, perioperative, complication, pathologic, and survival data were collected and analysed.

Results and limitations

Most tumours were transitional cell carcinoma (TCC; 160, 93.6%). Tumours were organ confined in 113 patients (pT1–T2; 66.1%) and non–organ confined in 58 patients (pT3–T4a; 33.9%). There was involvement of the lymph nodes in 38 patients (22.2%). Surgical margins were all tumour free. The mean number of removed lymph nodes was 16 (5–46). Follow-up ranged from 3 to 83 mo, and 54 (31.6%) patients completed 5-yr follow-up. Two patients (1.2%) had local recurrence and distant metastasis, 9 patients (5.3%) had local recurrence alone, and 23 patients (13.5%) had distant metastasis. One patient (0.6%) had port-site seeding. One hundred twenty-four patients (72.5%) were alive with no evidence of recurrence; 28 patients (16.4%) died, 20 from metastasis and 8 from tumour-unrelated causes. The estimated 5-yr overall survival, cancer-specific survival, and recurrence-free survival rates were 73.7%, 81.3%, and 72.6%, respectively. The relatively low percentage of patients reaching 5-yr follow-up is a limitation of this retrospective study.

Conclusions

Surgical technique of LRC with OIN can achieve the established oncologic criteria of open surgery, and our oncologic outcome is encouraging. Long-term follow-up is needed for further confirmation.     

Tumour Necrosis Is an Indicator of Aggressive Biology in Patients with Urothelial Carcinoma of the Upper Urinary Tract

Background

Prognostic factors after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) are inconclusive, because most data in the literature have been obtained from small series.

Objective

To assess the association of tumour necrosis with cancer recurrence and survival in a large international series of patients treated with RNU.

Design, setting, and participants

Data were collected from 1425 patients treated with RNU at 13 centres and combined into a relational database. Pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria. Extensive tumour necrosis was scored as >10% of the tumour area.

Intervention

Patients underwent either open or laparoscopic RNU. Lymph node dissection was performed in the presence of enlarged nodes.

Measurements

Recurrence was defined as tumour relapse in the operative field, lymph node (LN) metastasis, and/or distant metastases. Bladder recurrences were not considered. Associations of extensive tumour necrosis with recurrence-free survival and cancer-specific survival were evaluated by univariate and multivariate analyses.

Results and limitations

Extensive tumour necrosis was observed in 364 patients (25.5%) and was associated with advanced tumour stage, high tumour grade, sessile architecture, lymphovascular invasion (LVI), concomitant carcinoma in situ, and LN metastasis (p < 0.0001 each). Extensive tumour necrosis was independently associated with disease recurrence and survival (p = 0.037 and p = 0.046, respectively) after adjusting for the effects of pathologic stage, grade, LVI, and LN status. The addition of extensive tumour necrosis to a base model comprising standard pathologic predictors marginally improved its predictive accuracy for both cancer-specific recurrence (1.5%) and survival (1.4%).

Conclusions

Extensive tumour necrosis is an independent predictor of clinical outcomes in patients who undergo RNU for UTUC. Assessment of tumour necrosis may help to identify patients who could benefit from multimodal therapy after RNU in the future. Evaluation of extensive tumour necrosis should be part of standard pathologic reporting.     

Implicaciones pronósticas del estudio estandarizado de los márgenes de resección en el cáncer de páncreas

Introduction

Involvement of surgical resection margins is a fundamental prognostic factor in pancreatic oncological surgery. However, there is a lack of standardized histopathology definition. The aims of this study are to investigate the real rate of R1 resections when surgical specimens are evaluated according to a standardized protocol and to study its survival implications.

Patients y methods

One hundred consecutive surgically resected patients with pancreatic ductal adenocarcinoma were included in the study. They were further divided in 2 groups: pre-protocol, evaluated before the introduction of the standardized protocol and post-protocol, analyzed with the standardized protocol.

Results

R0 resection rate in the pre-protocol group was 78%, falling to 47% after the introduction of the standardized protocol (p = 0,003). The posterior retroperitoneal margin was the most frequently involved margin. In cases with tumors located at the pancreatic head and analyzed according to the standardized protocol R1 involvement negatively affected survival. Median survival in the R0 group was 22 months versus 16 in those with the margin involved (HR: 2.044; IC 95% 1,00-4,16; P=.043).

Conclusions

Standardized evaluation of the retroperitoneal margins in pancreatic cancer increases the rate of R1 patients. In cases with pancreatic cancer located at the pancreatic head involvement of posterior retroperitoneal margin significantly decreases survival.     

Modified Glasgow prognostic score in patients with incurable stage IV colorectal cancer

Background

The modified Glasgow prognostic score is an inflammation-based prognostic score. This study examined whether this score, measured before surgical procedures, could predict postoperative cancer-specific survival.

Methods

We retrospectively studied 79 colorectal cancer patients who underwent a surgical procedure for incurable stage IV disease. The modified Glasgow prognostic score (0 to 2) comprises C-reactive protein (≤10 vs >10 mg/L) and albumin (<35 vs ≥35 g/L) measurements.

Results

In terms of overall survival, univariate analysis revealed significant differences in the status of lung metastasis, peritoneal dissemination, distant metastasis, hemoglobin, C-reactive protein, albumin, tumor resection, adjuvant chemotherapy, and modified Glasgow prognostic score. Multivariate analysis revealed that hemoglobin (P = .019), adjuvant chemotherapy (P = .002), and modified Glasgow prognostic score (0 and 1, low; 2, high) (P = .0001) were significant predictive factors for postoperative mortality.

Conclusions

The modified Glasgow prognostic score is simple to obtain and useful in predicting survival in incurable stage IV colorectal cancer patients undergoing surgery.     

Long-term Outcomes of Patients with Lymph Node Metastasis Treated with Radical Prostatectomy Without Adjuvant Androgen-deprivation Therapy

Background

The presence of lymph node metastasis (LNM) at radical prostatectomy (RP) is associated with poor outcome, and optimal treatment remains undefined. An understanding of the natural history of node-positive prostate cancer (PCa) and identifying prognostic factors is needed.

Objective

To assess outcomes for patients with LNM treated with RP and lymph node dissection (LND) alone.

Design, setting, and participants

We analyzed data from a consecutive cohort of 369 men with LNM treated at a single institution from 1988 to 2010.

Intervention

RP and extended LND.

Outcome measurements and statistical analysis

Our primary aim was to model overall survival, PCa-specific survival, metastasis-free progression, and freedom from biochemical recurrence (BCR). We used univariate Cox proportional hazard regression models for survival outcomes. Multivariable Cox proportional hazard regression models were used for freedom from metastasis and freedom from BCR, with prostate-specific antigen, Gleason score, extraprostatic extension, seminal vesical invasion, surgical margin status, and number of positive nodes as predictors.

Results and limitations

Sixty-four patients with LNM died, 37 from disease. Seventy patients developed metastasis, and 201 experienced BCR. The predicted 10-yr overall survival and cancer-specific survival were 60% (95% confidence interval [CI], 49–69) and 72% (95% CI, 61–80), respectively. The 10-yr probability of freedom from distant metastasis and freedom from BCR were 65% (95% CI, 56–73) and 28% (95% CI, 21–36), respectively. Higher pathologic Gleason score (>7 compared with ≤7; hazard ratio [HR]: 2.23; 95% CI, 1.64–3.04; p < 0.0001) and three or more positive lymph nodes (HR: 2.61; 95% CI, 1.81–3.76; p < 0.0001) were significantly associated with increased risk of BCR on multivariable analysis. The retrospective nature and single-center source of data are study limitations.

Conclusions

A considerable subset of men with LNM remained free of disease 10 yr after RP and extended LND alone. Patients with pathologic Gleason score <8 and low nodal metastatic burden represent a favorable group. Our data confirm prior findings and support a plea for risk subclassification for patients with LNM.     

Diferencias entre cirugía en bloque y enucleación en el tratamiento del sarcoma retroperitoneal

Aim

Today, free margin surgery is the gold-standard management for soft-tissue sarcoma patients and one of the most important predictors of recurrence and survival. To obtain optimal results, a multidisciplinary approach is necessary. The aim of this study was to evaluate the evolution of patients with RPS treated by «en bloc«surgical resection versus those treated with enucleation in the first surgery.

Methods

Fifty-six adult patients were divided into 2 groups. Patients in Group A underwent enucleation surgery, and patients in Group B underwent en bloc surgery. The endpoints of the study were survival time and time to recurrence, according to histological type and first surgical strategy.

Results

Disease-free survival was longer for en bloc surgery (P<0,05), but there was no difference in overall survival. When comparing the histology of patients who underwent enucleation surgery and en bloc resection surgery, the disease-free survival and overall survival rates were longer for liposarcoma. In the multivariate analysis, only free margins and histology of liposarcoma were significantly associated with a better survival.

Conclusions

The surgical management of patients with retroperitoneal sarcoma must be very aggressive, often requiring multivisceral resection. Considering the disease-free survival and overall survival rates obtained, it is clear that it is critical to manage patients as early as possible by a radical en bloc surgery.     

Positive surgical margins after nephron-sparing surgery

Context

Little is known on the natural history of positive surgical margins (PSMs) in partial nephrectomy (PN). Accumulating data suggest that secondary nephrectomy might not be necessary in all patients with PSMs after PN.

Objective

Provide an overview on incidence and risk factors for PSMs after partial nephrectomy and on the rate of local and distant disease recurrence related to PSMs. We also provide recommendations on how to avoid and how to treat PSMs after PN.

Evidence acquisition

A nonsystematic literature research was based on Medline, Scopus, and Web of Science queries on these keywords: nephron-sparing surgery, partial nephrectomy/ies, and margin. Only human studies (original research) published in English were included.

Evidence synthesis

PSMs are present in 0–7% of patients after open PN, in 0.7–4% after laparoscopic PN, and in 3.9–5.7% after robot-assisted PN. The thickness of healthy parenchyma surrounding the tumour is irrelevant as long as complete tumour removal is achieved. The coincidence of a highly malignant tumour and PSM increases the risk of local recurrence. Intermediate follow-up data indicate that the vast majority of patients with PSMs will not experience local or distant tumour recurrence. Frozen-section analysis for evaluation of resection margins during PN is of minor clinical significance, as the surgeon's gross assessment of macroscopically negative margins provides reliable results.

Conclusions

PSMs in PN are rare. As indicated by intermediate follow-up data, the majority of patients with PSMs after PN remain without disease recurrence, and a surveillance strategy seems preferable to surgical reintervention.     

Metastasectomy of neuroendocrine tumors in patients with multiple endocrine neoplasia type 1

Background

Neuroendocrine (NE) tumors commonly afflict patients with multiple endocrine neoplasia type 1 (MEN1). It is thought that patients with MEN1 have improved survival compared with individuals with analogous lesions. The role of metastasectomy of NE tumors in MEN1 patients is not clearly defined.

Methods

A review of MEN1 patients undergoing surgery for NE tumors from 1994 to 2010 at a single tertiary care center was performed. Tumor function, the extent of metastasis, R0 resection, and survival were analyzed.

Results

We identified 30 patients who underwent resection including synchronous and metachronous metastasectomy. Synchronous metastases were identified in 19 patients (63%), whereas 11 (37%) had metachronous disease. R0 resection was achieved in 93% of patients. Estimated 10-year survival is 86.4% (95% confidence interval, 60% to 100%) with no factors predictive of overall survival. The disease-free interval at 1, 5, and 10 years was 89%, 50%, and 19%, respectively, with recurrence occurring at a median of 5.4 years (95% confidence interval, 77.7% to 100%). Synchronous metastasis (P = .0072; hazard ratio [HR], 3.4) and nonfunctioning tumors (P = .014; HR, 3.3) were more likely to recur, whereas age (P = .09; HR, 1.5), gender (P = .49; HR, 1.3), and the site of metastasis (P = .81; HR, 1.1) did not influence recurrence.

Discussion

Patients with MEN1 benefit from resection of metastatic NE disease. Despite a high recurrence rate, survival and disease-free interval is favorable vs patients without MEN1.     

Surgery for Metastatic Urothelial Carcinoma with Curative Intent: The German Experience (AUO AB 30/05)

Background

Recent publications suggest a benefit from surgical removal of urothelial carcinoma metastases (UCM) for a subgroup of patients.

Objective

We report the combined experience and outcome of patients undergoing resection of UCM gained at 15 uro-oncologic centers in Germany.

Design, setting, and participants

Retrospective survey of 44 patients with distant UCM of the bladder or upper urinary tract who underwent complete resection of all detectable metastases in 15 different German uro-oncological centers between 1991 and 2008.

Intervention

Resected metastatic sites were the following: retroperitoneal lymph nodes (56.8%), distant lymph nodes (11.3%), lung (18.2%), bone (4.5%), adrenal gland (2.3%), brain (2.3%), small intestine (2.3%), and skin (2.3%). Systemic chemotherapy was administered in 35 of 44 patients (79.5%) before and/or after UCM surgery.

Measurements

Overall, cancer-specific and progression-free survival from time of diagnosis and metastasectomy of UCM.

Results and limitations

Median survival from initial diagnosis of UCM and subsequent resection was as follows: overall survival, 35 mo and 27 mo; cancer-specific survival, 38 mo and 34 mo; and progression-free survival, 19 mo and 15 mo. Overall 5-yr survival from metastasectomy for the entire cohort was 28%. Seventeen patients were still alive without progression at a median follow-up of 8 mo. Seven patients without disease progression survived for >2 yr and remained free from tumor progression at a median follow-up of 63 mo. No significant prognostic factors could be determined due to the limited patient number.

Conclusions

Long-term cancer control and possible cure can be achieved in a subgroup of patients following surgical removal of UCM. Metastasectomy in patients with disseminated UCM remains investigational and should only be offered to those with limited disease as a combined-modality approach with systemic chemotherapy.     

Prognostic Value of Perinodal Lymphovascular Invasion Following Radical Cystectomy for Lymph Node–positive Urothelial Carcinoma

Background

Metastasis of urothelial carcinoma of the bladder (UCB) into regional lymph nodes (LNs) is a key prognosticator for cancer-specific survival (CSS) after radical cystectomy (RC). Perinodal lymphovascular invasion (pnLVI) has not yet been defined.

Objective

To assess the prognostic value of histopathologic prognostic factors, especially pnLVI, on survival.

Design, setting, and participants

A total of 598 patients were included in a prospective multicentre study after RC for UCB without distant metastasis and neoadjuvant and/or adjuvant chemotherapy. En bloc resection and histopathologic evaluation of regional LNs were performed based on a prospective protocol. The final study group comprised 158 patients with positive LNs (26.4%).

Intervention

Histopathologic analysis was performed based on prospectively defined morphologic criteria of LN metastases.

Outcome measurements and statistical analysis

Multivariable Cox proportional hazard regression models determined prognostic impact of clinical and histopathologic variables (age, gender, tumour stage, surgical margin status, pN, diameter of LN metastasis, LN density [LND], extranodal extension [ENE], pnLVI) on CSS. The median follow-up was 20 mo (interquartile range: 11–38).

Results and limitations

Thirty-one percent of patients were staged pN1, and 69% were staged pN2/3. ENE and pnLVI was present in 52% and 39%, respectively. CSS rates after 1 yr, 3 yr, and 5 yr were 77%, 44%, and 27%, respectively. Five-year CSS rates in patients with and without pnLVI were 16% and 34% (p < 0.001), respectively. PN stage, maximum diameter of LN metastasis, LND, and ENE had no independent influence on CSS. In the multivariable Cox model, the only parameters that were significant for CSS were pnLVI (hazard ratio: 2.47; p = 0.003) and pT stage. However, pnLVI demonstrated only a minimal gain in predictive accuracy (0.1%; p = 0.856), and the incremental accuracy of prediction is of uncertain clinical value.

Conclusions

We present the first explorative study on the prognostic impact of pnLVI. In contrast to other parameters that show the extent of LN metastasis, pnLVI is an independent prognosticator for CSS.     

Association of Positive Transection Margins with Gastric Cancer Survival and Local Recurrence

Purpose

To examine the association between positive resection margins and survival and local recurrence in patients with gastric cancer undergoing resection with curative intent.

Methods

Patients who underwent curative intent resection for gastric carcinoma from 1985 to 2010 were identified from a prospectively maintained database. Positive margins were defined as disease present at the line of luminal transection. Clinicopathological features and outcome of patients undergoing gastrectomy with negative and positive margins were compared.

Results

Among 2384 patients undergoing curative intent resection, 108 (4.5 %) had positive margins. Positive margins were associated with higher American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number of positive nodes, diffuse Lauren type, and poorly differentiated tumors. Treatment of positive margins consisted of: observation (39 %), chemoradiotherapy (26 %), chemotherapy (20 %), repeat resection (10 %), radiotherapy (4 %), and unknown (1 %). Multivariate analysis of the entire cohort demonstrated margin status, T stage, N stage, grade, and perineural invasion to be independent predictors of survival. Margin status was an independent predictor of survival in patients with ≤3 positive nodes or T1–2 disease but was not in patients with >3 positive nodes or T3–4 disease. Local recurrence occurred in 16 % of patients with a positive margin. We identified no factors predictive of local recurrence in patients with positive margins.

Conclusions

Positive resection margin is associated with advanced AJCC stage and aggressive tumor biology but remains an independent predictor of worse survival. The significance of a positive margin in gastric cancer is confined to patients with nontransmural disease and/or limited nodal involvement.

     

Prognostic factors for survival after salvage surgery for locoregional recurrence of colon cancer

Background

Although locoregional recurrence after rectal cancer resection has been extensively investigated, studies of salvage surgery for locoregionally recurrent colon cancer are scarce. This study aimed to determine the predictors of postsalvage survival for locoregionally recurrent colon cancer.

Methods

We studied 45 consecutive patients who underwent macroscopically complete resection of locoregionally recurrent colon cancer between April 1988 and December 2007. The primary end point was cancer-specific survival, and 20 clinical variables were analyzed for their prognostic significance.

Results

Cancer-specific 5-year survival for the entire cohort of 45 patients was 46%. Multivariate survival analysis showed that margin status (P = .0311), number of locoregional recurrent tumors (P = .0002), pathological grade (P = .0416), largest tumor diameter (P = .0247), and distant metastasis (P = .0006) were independently associated with cancer-specific survival.

Conclusions

Salvage surgery for locoregional recurrence of colon cancer can provide a chance for long-term survival in selected patients.     

Recurrence after curative-intent resection of perihilar cholangiocarcinoma: analysis of a large cohort with a close postoperative follow-up approach

Background

Although several studies have been conducted on the patterns of recurrence in resected perihilar cholangiocarcinoma, they have many limitations. The aim of this study was to investigate recurrence after resection and to evaluate prognostic factors on the time to recurrence and recurrence-free survival.

Bladder Preservation in Selected Patients with Muscle-Invasive Bladder Cancer by Complete Transurethral Resection of the Bladder Plus Systemic Chemotherapy: Long-Term Follow-up of a Phase 2 Nonrandomized Comparative Trial with Radical Cystectomy

Background

Many phase 2 bladder-sparing programmes using transurethral resection of the bladder (TURB) plus chemotherapy or radio-chemotherapy have been undertaken, but some controversies remain.

Objective

To determine the efficacy of complete TURB plus three cycles of cisplatin-based chemotherapy in selected patients with muscle-invasive bladder cancer (MIBC).

Design, setting, and participants

A phase 2 nonrandomized trial was designed that included patients with MIBC who underwent complete TURB with positive biopsies of the tumour bed. Patients with negative biopsies of the tumour bed, with macroscopically residual tumour, with hydronephrosis, or with distant metastasis were excluded from this trial. Patients included in this trial were offered three cycles of systemic chemotherapy or radical cystectomy (RC). Clinical response (cR) was denoted by either no tumour or the presence of Ta1–Tis bladder tumour at 3-mo evaluation; clinical non-response (cNR) was denoted by cases of muscle-invasive tumour or distant metastasis. Of 146 patients who entered this trial, 75 choose the bladder-sparing programme and 71 chose RC.

Measurements

At 5 yr and 10 yr, the cancer-specific survival (CSS) rate was 64.5% and 59.8%, respectively, with no significant difference compared to the RC arm (p = 0.544). The progression-free survival with bladder preserved was 52.6% and 34.5%, respectively. In multivariate analysis, cR was the only predictive factor for survival (p = 0.001) and bladder preservation (p = 0.000).

Results and limitations

This was not a randomized trial, and patients were included over 16 yr. However, no modifications were made to the therapy schedule except from chemotherapy schemes considered standard at the time.

Conclusions

Patients with microscopic residual cancer after complete TURB seem to be good candidates for the bladder-sparing programme using three cycles of systemic chemotherapy, with CSS comparable to RC.     

Extranodal Extension Is a Powerful Prognostic Factor in Bladder Cancer Patients with Lymph Node Metastasis

Background

Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable.

Objective

To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters.

Design, setting, and participants

A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo).

Intervention

All subjects underwent RC and bilateral pelvic lymphadenectomy.

Outcome measurements and statistical analysis

Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC.

Results and limitations

A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p < 0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55–2.31; p < 0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52–2.37; p < 0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% (p < 0.001) and from 71.8% to 77.8% (p = 0.007), respectively. The main limitation of the study is its retrospective nature.

Conclusions

ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC.     

Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences

Context

This review focuses on positive surgical margins (PSM) in radical prostatectomy (RP).

Objective

To address the etiology, incidence, and oncologic impact of PSM and discuss technical points to help surgeons minimize their positive margin rate. An evidence-based approach to assist clinicians in counseling patients with a PSM is provided.

Evidence acquisition

A literature search in English was performed using the National Library of Medicine database and the following key words: prostate cancer, surgical margins, and radical prostatectomy. Seven hundred sixty-eight references were scrutinized, and 73 were selected for rigorous review based on their pertinence, study size, and overall contribution to the field.

Evidence synthesis

In contemporary series, PSM are reported in 11–38% of patients undergoing RP. Although variability exists in the pathologic interpretation of surgical margins, PSM are associated with an increased hazard of biochemical recurrence (BCR) and local disease recurrence as well as the need for secondary cancer treatment. A posterolateral PSM appears to confer the greatest risk of recurrence, whereas the prognostic significance of positive apical margins remains controversial. The role of preoperative imaging and intraoperative frozen section analysis are being investigated to reduce margin positivity rates. Level-1 evidence indicates that adjuvant radiotherapy (RT) in men with PSM reduces BCR rates and clinical progression and possibly improves overall survival (OS).

Conclusions

PSM in RP specimens are uniformly considered an adverse outcome. Regardless of approach (open or laparoscopic), attention to surgical detail is essential to minimize rates. For patients with a PSM destined to experience a cancer recurrence, RT is the only established treatment with curative potential. A randomized trial in patients with PSM comparing immediate postoperative RT to salvage RT is critically needed before definitive recommendations can be made.     

Oncologic Outcomes Following Three Different Approaches to the Distal Ureter and Bladder Cuff in Nephroureterectomy for Primary Upper Urinary Tract Urothelial Carcinoma

Background

There is a lack of consensus regarding the prognostic significance of different approaches to the bladder cuff at surgery for primary upper urinary tract urothelial carcinoma (UUT-UC).

Objectives

To compare the oncologic outcomes following radical nephroureterectomy using three different methods of managing the bladder cuff.

Design, setting, and participants

From January 1990 to December 2007, 414 patients with primary UUT-UC underwent radical nephroureterectomy at our institution. Of these, 301 were included in our study.

Intervention

Three methods of bladder cuff excision—intravesical incision, extravesical incision, and transurethral incision (TUI)—were performed.

Measurements

Patients’ medical records were reviewed retrospectively. The clinicopathologic data and oncologic outcomes were compared among groups.

Results and limitations

Of the 301 patients, 81 (26.9%) underwent the intravesical method, 129 (42.9%) underwent the extravesical technique, and 91 (30.2%) underwent TUI. There were no differences in clinical and histopathologic data among the three groups. When comparing the intravesical, extravesical, and TUI techniques, bladder recurrence developed in, respectively, 23.5%, 24.0%, and 17.6% cases (p = 0.485); local retroperitoneal recurrence in 7.4%, 7.8%, and 5.5% (p = 0.798); contralateral recurrence in 4.9%, 3.9%, and 2.2% (p = 0.632); and distant metastasis in 7.4%, 10.4%, and 5.5% (p = 0.564). There were no differences in recurrence-free and cancer-specific survival among the three groups (p = 0.680 and 0.502, respectively).

Conclusions

The three techniques had comparable oncologic outcomes. Our data validate the TUI method of bladder cuff control in patients with primary UUT-UC without coexistent bladder tumors.     

Long-term survival after resection of primary adenoid cystic and squamous cell carcinoma of the trachea and carina

Background

Tracheal resection for primary carcinoma may extend survival. We evaluated survival after surgical resection or palliative therapy to identify prognostic factors.

Methods

We conducted a retrospective study of patients diagnosed with primary adenoid cystic carcinoma (ACC) or squamous cell carcinoma (SCC) of the trachea between 1962 and 2002. Laryngotracheal, tracheal, or carinal resection was performed when distant metastasis and invasion of adjacent mediastinal structures were absent and tumor length permitted. Radiotherapy was administered after operation (54 Gy), except in superficial tumors, or as palliation (60 Gy).

Results

Of 270 patients with ACC or SCC (135 each), 191 (71%) were resected. Seventy-nine were not resected due to tumor length (67%), regional extent (24%), distant metastasis (7%), or other reasons (2%). Overall operative mortality was 7.3% (14/191) and improved each decade from 21% to 3%. Tumor in airway margins was present in 40% (17/191) of resected patients (ACC 59% versus SCC 18%) and lymph node metastasis in 19.4% (37/191). Overall 5- and 10-year survival in resected ACC was 52% and 29% (unresectable 33% and 10%) and in resected SCC 39% and 18% (unresectable 7.3% and 4.9%). Multivariate analysis of long-term survival found statistically significant associations with complete resection (p < 0.05), negative airway margins (p < 0.05), and adenoid cystic histology (p < 0.001), but not with tumor length, lymph node status, or type of resection.

Conclusions

Locoregional, not distant, disease determines resectability in primary tracheal carcinoma. Resection of trachea or carina is associated with long-term survival superior to palliative therapy, particularly for patients with complete resection, negative airway margins, and ACC.     

Primary Gleason Grade 4 at the Positive Margin Is Associated with Metastasis and Death Among Patients with Gleason 7 Prostate Cancer Undergoing Radical Prostatectomy

Background

The presence of a positive surgical margin (PSM) at radical prostatectomy (RP) has been linked to an increased risk of biochemical recurrence and receipt of secondary therapy; however, its association with other oncologic end points remains controversial.

Objective

To evaluate the association of primary Gleason grade (GG) at the site of PSM with subsequent clinical progression and mortality among patients with Gleason score (GS) 7 prostate cancer (PCa).

Design, setting, and participants

We identified 1036 patients who underwent RP between 1996 and 2002. A single uropathologist re-reviewed all specimens noted to have a PSM to record GG at the margin.

Outcome measurements and statistical analysis

Survival was estimated using the Kaplan-Meier method. Cox models were used to analyze the association of margin primary GG with outcome.

Results and limitations

Overall, 338 men (33%) had a PSM; of those, 242 had PSM GG3 and 96 had PSM GG4. Median postoperative follow-up was 13 yr. Compared with men with PSM GG3 or a negative SM, we noted that men with PSM GG4 had significantly worse 15-yr systemic progression-free survival (74% vs 90% vs 93%, respectively; p < 0.001) and cancer-specific survival (86% vs 96% vs 97%, respectively; p = 0.002). On multivariable analysis, the presence of PSM GG4 was associated with increased risks of systemic progression (hazard ratio [HR]: 2.77; p = 0.003) and death from PCa (HR: 3.93; p = 0.02) among men with a PSM. Limitations include the relatively small rate of disease recurrence.

Conclusions

PSM primary GG4 was independently associated with adverse oncologic outcomes among men with GS7 PCa. Pending external validation, GG at the PSM may be considered for inclusion in pathologic reports and risk stratification following RP.

Patient summary

Among patients with Gleason grade 7 prostate cancer and a positive surgical margin at the time of prostatectomy, we found that higher Gleason grade at the margin was associated with worse oncologic outcomes.