Local Recurrence-free Research Articles

Effects of Postoperative Adjuvant Radiotherapy on Recurrence and Survival in Stage III Rectal Cancer

BackgroundThe aim of this study is to evaluate whether the addition of radiotherapy to chemotherapy would enhance the benefits obtained with chemotherapy alone, in stage III rectal cancer in the era of preoperative chemoradiotherapy and total mesorectal excision (TME). MethodsFrom January 1999 to January 2008, 300 stage III rectal cancer patients who underwent TME were prospectively identified; a total of 46 patients who received preoperative chemoradiotherapy or did not receive adjuvant therapy were excluded. Patients who received postoperative chemotherapy alone (n=190) and those who received postoperative chemoradiotherapy (n=64) were compared. ResultsThe median follow-up period was 52 (range, 4–129) months. Patients receiving radiotherapy were younger and had a higher percentage of advanced pT category or perineural invasion than patients who did not. The estimated 5-year local recurrence-free survival rate was radiotherapy 92% with radiotherapy and 86% without. The disease-free survival rate was 55% with radiotherapy compared to 57% without and the overall survival rates were similar (63% vs. 68%, all P>0.05). In patients with a positive circumferential resection margin or insufficient distal resection margin, the local recurrence-free, disease-free, and overall survival rates were unaffected by radiotherapy. ConclusionsThe addition of postoperative radiotherapy to chemotherapy did not reduce the recurrence or mortality in node-positive rectal cancer when compared with chemotherapy alone. Moreover, this approach may not compensate for a positive circumferential resection margin or insufficient distal resection margin following rectal cancer surgery.

Assessment of tumour resection margins using optical coherence tomography

In the treatment of cancer, the fundamental surgical goal is to remove all local malignant disease and leave no residual malignant cells. Studies have demonstrated the benefit of achieving negative resection margins in terms of disease free local recurrence and overall survival. The surgical margins for head & neck cancer may vary widely depending on the site of disease. Optical coherence tomography (OCT) is an imaging modality that uses light to determine cross-sectional anatomy in turbid media such as living tissues. In this study, we used this technology to evaluate resection margins acquired from patients with oral squamous cell cancer (OSCC).

Clinical and Treatment Outcomes of Planned and Unplanned Excisions of Soft Tissue Sarcomas

Soft tissue sarcomas are often inappropriately excised without adequate preoperative planning. Inappropriate (unplanned) excisions may adversely affect local recurrence, distant metastasis, patient survival, and /or postoperative function once properly evaluated. We asked whether the clinical and treatment characteristics, survival (overall, local recurrence-free, distant metastasis-free), and functional scores of patients with unplanned excisions differ from those with a planned excision. We retrospectively reviewed 128 patients with planned excisions and 63 patients with unplanned excisions at prereferral hospitals followed by additional reexcisions. We determined whether age, gender, tumor size, depth, histologic grade, operative duration, blood loss, survival, or functional scores differed between the two groups. The minimum followup was 6 months (mean, 55 months; range, 6-275 months). The tumor was larger and its location deeper in the planned excision group. Overall, metastasis-free, and local recurrence-free survival were similar in the two groups: 86%, 71%, and 85% in the planned excision group and 96%, 86%, and 92% in the unplanned excision group, respectively. However, additional soft tissue reconstruction was more often necessary for patients with unplanned excisions. No difference in postoperative function was observed. The data suggest an adequate additional wide excision may improve the local control and survival in patients with an unplanned excision as well as the patients with a planned excision. While patients with unplanned excisions had superficial and smaller tumors, survival and postoperative function were similar to those with planned excisions.

Local Excision Following Pre-operative Chemoradiotherapy-induced Downstaging for Selected cT3 Distal Rectal Cancer

To investigate the long-term outcomes of selected patients with cT3 distal rectal cancer treated with local excision following pre-operative chemoradiotherapy. Between January 2003 and February 2008, 11 patients with cT3 distal rectal cancer received a local excision following pre-operative chemoradiotherapy. The median age of the patients was 61 years (range, 42-71). The median tumor size was 3 cm (range, 2-5), and the median distance of the caudal tumor edge from the anal verge was 3 cm (range, 1-4). Clinical lymph node status was positive in five patients. Pre-operative chemoradiotherapy consisted of a 50.4 Gy in 28 fractions with concurrent chemotherapy. A transanal full-thickness local excision was performed after a median of 54 days (range, 31-90) from chemoradiotherapy completion. Ten patients received post-operative chemotherapy. Pathologically complete responses occurred in eight patients, ypT1 in two and ypT2 in one. The pathologic tumor size for three ypT1-2 tumors was 0.9, 1.1 and 2.2 cm. The follow-up period was a median of 59 months (range, 24-85). One patient (ypT0) developed recurrence at the excision site 14 months after surgery, but was successfully salvaged with an abdominoperineal resection and adjuvant chemotherapy. Another patient (ypT2) developed bone metastasis after 8 months and died of the disease. The 5-year local recurrence-free, disease-free and overall survival rates were 90.9%, 81.8% and 88.9%, respectively. No Grade 3 or worse gastrointestinal toxicity was detected. Full-thickness local excision following chemoradiotherapy may be an acceptable option for cT3 distal rectal cancer that responds well to chemoradiotherapy.

Efficacy of a hypofractionated schedule in electron beam radiotherapy for epithelial skin cancer: Analysis of 434 cases

Background and purpose Efficacy of radiotherapy for epithelial skin cancer was evaluated and treatment outcomes of two electron beam fractionation schedules were compared. Materials and methods Outcome data of 434 epithelial skin cancers in 333 patients were analysed; 332 were basal cell carcinomas (BCCs) and 102 squamous cell carcinomas (SCCs). Patients were treated with electron beam, and received either 54 Gy in 18 fractions ( n = 159) or 44 Gy in 10 fractions ( n = 275). Local recurrence free (LRF) rates were analysed as well as metastases free rates, cancer specific survival (CSS) and cosmetic result. Results Median follow-up was 42.8 months. For BCC, actuarial 3-year LRF rates were 97.6% for tumours treated with 54 Gy and 96.9% for 44 Gy. In SCC 3-year LRF rates were 97.0% for 54 Gy and 93.6% for 44 Gy (n.s.). T stage was found to be the only significant factor for recurrence ( p = 0.036). Three-year CSS was 98% for SCC and 100% for BCC. Conclusions Electron beam irradiation is a safe and effective treatment modality for epithelial skin cancer. In view of a similar efficacy and patient convenience of the hypofractionated schedule, 44 Gy in 10 fractions can be regarded the radiation schedule of choice.

The surgical resection margin

In the treatment of cancer the fundamental surgical goal is to remove all local malignant disease and leave no residual malignant cells. Studies have demonstrated the benefit of achieving negative resection margins in terms of disease free local recurrence and overall survival. The surgical margins for Head & Neck cancer may vary widely depending on the site of disease. This variation reflects the biological and anatomical environment of the tumour site at macroscopic and microscopic levels. There is no accepted standard for the quantity of normal tissue to be removed and the effect of positive margins on recurrence rate appears to be considerably dependent on the site of the tumour. The extent of tumour volume resection is determined by the need for cancer control and the peri-operative, functional and aesthetic morbidity of the surgery. Resection margins are assessed intra-operatively by frozen section and retrospectively after definitive histological analysis of the resection specimen. There are limitations to this assessment. The margin may not be consistent in three dimensions and may be susceptible to errors in sampling and histological interpretation. Assigning the true excision margin may be difficult due to post-excision changes secondary to shrinkage and fixation. Local recurrence occurs even among tumours with extensive histological demonstration of adequate resection margins. Sites with significant recurrence rates after negative resection margins are oral cavity, submandibular region, tonsil and pharynx. Therefore, it is accepted that cancers at these sites require larger margins of excision than tumours elsewhere in the head and neck. Achieving the histologically adequate margin is insufficient to predict clinical outcome. Multiple parameters in the histological assessment have been developed and refined to predict outcome based on a number of variables including pattern of invasion, keratinisation, nuclear pleomorphism and mitotic rate. Recently molecular technology has been employed to provide a more objective assessment of the margins but these techniques are not yet validated. The current approaches to histological risk assessment and evaluation of the surgical margin in Head & Neck cancer and the limitations will be discussed.

Validation of Radiation Volume by Analysis of Recurrence Pattern in Breast-conserving Treatment for Early Breast Cancer

Purpose: To assess the appropriateness of radiotherapy volume for patients receiving breast-conserving treatment (BCT) through analysis of recurrence pattern and factors affecting recurrence. Methods: From 1991 to 1996, 362 patients who received BCT were retrospectively evaluated. The radiation volume was the involved breast alone in the patients with less than 4 positive axillary lymph nodes (LNs), and breast and supraclavicular fossa in patients with 4 or more positive axillary LNs. The median follow-up period was 123 months (range, 3-169 months). Results: Ten-year overall, disease-free, local recurrence-free, and regional recurrence-free survival rates were 86.2%, 82.2%, 95.9%, and 95.2%, respectively. Among 310 patients receiving radiotherapy on the breast alone, 15 (4.8%) had regional recurrence. In particular, patients with inner quadrant lesions had high regional recurrence rates (11/98, 11.2%) (p <0.001). Conclusion: These low local recurrence rates may reveal that the current radiotherapy technique was successful. However, in cases of inner quadrant lesions, there were a considerable number of regional recurrences, even in N0 cases. This may suggest a potential role for irradiation on regional LNs in this group.

Radiotherapy With 8-MHz Radiofrequency-Capacitive Regional Hyperthermia for Stage III Non–Small-Cell Lung Cancer: The Radiofrequency-Output Power Correlates With the Intraesophageal Temperature and Clinical Outcomes

To assess the efficacy of radiotherapy (RT) combined with regional hyperthermia (HT) guided by radiofrequency (RF)-output power and intraesophageal temperature and evaluate the potential contribution of HT to clinical outcomes in patients with Stage III non-small-cell lung cancer (NSCLC). Thirty-five patients with Stage III NSCLC treated with RT plus regional HT were retrospectively analyzed. Twenty-two of the 35 patients underwent intraesophageal temperature measurements. Patients with subcutaneous fat of 2.5 cm or greater, older age, or other serious complications did not undergo this therapy. The 8-MHz RF-capacitive heating device was applied, and in all patients, both the upper and lower electrodes were 30 cm in diameter, placed on opposite sides of the whole thoracic region, and treatment posture was the prone position. The HT was applied within 15 minutes after RT once or twice a week. All thermal parameters, minimum, maximum, and mean of the four intraesophageal temperature measurements at the end of each session and the proportion of the time during which at least one of the four intraesophageal measurements was 41 degrees C or higher in the total period of each session of HT, of the intraesophageal temperature significantly correlated with median RF-output power. Median RF-output power (>/=1,200 W) was a statistically significant prognostic factor for overall, local recurrence-free, and distant metastasis-free survival. The RT combined with regional HT using a higher RF-output power could contribute to better clinical outcomes in patients with Stage III NSCLC. The RF-output power thus may be used as a promising parameter to assess the treatment of deep regional HT if deep heating using this device is performed with the same size electrodes and in the same body posture.

Postoperative External Beam Radiotherapy for Retroperitoneal Soft Tissue Sarcoma

Purpose: To evaluate the clinical outcomes and prognostic factors in retroperitoneal soft tissue sarcomas treated by postoperative radiotherapy. Materials and Methods: The records of 23 patients with retroperitoneal soft tissue sarcomas, who underwent postoperative radiotherapy between 1985 and 2003, were analyzed. The median follow-up period was 77 months (range, 8∼240 months). A total of 21 patients presented with primary dise ase, and two patients presented with recurrent disease. Liposarcomas and leiomyosarcomas represented 78% of the diagnosed tu- mor cases. Moreover, 17 cases were of high grade (grade 2 or 3). The median tumor size was 13 cm (range, 3∼ 50 cm). Complete excision was achieved in 65% of patients. The median radiation dose was 50.4 Gy (range, 45.0 to 59.4 Gy), with conventional fractionation. Results : The 5-year overall, local recurrence-free, and distant metastasis-free survival rates were 68%, 58%, and 71%, respectively. Eleven patients experienced local recurrence, while 9 patients experienced distant metastasis. The most common site for distant metastasis was the liver. A univariate analysis revealed that adjacent organ invasion and age (>60 years) as the significant risk factors contributing to the prediction of poor overall survival. Moreover, multivariate analyses indicated that adjacent organ invasion remained sig- nificantly associated with a higher risk of death. In addition, patient age (>60 years) was the other identified risk factor for local recurrence by univariate and multivariate analyses. Except for one case of grade 3 diar- rhea, no patient suffered grade 3 or higher complications. Conclusion : Our results were comparable to previous reports in that adjacent organ invasion and patient age (>60 years) were significant predictors of poor survival and tumor recurrence, respectively.

Long-Term Results of Two Prospective Trials of Preoperative External Beam Radiotherapy for Localized Intermediate- or High-Grade Retroperitoneal Soft Tissue Sarcoma

The reported data on surgery plus radiotherapy for retroperitoneal soft tissue sarcomas (RPS) have been mostly from retrospective studies. We evaluated the long-term outcome of patients with operable RPS who were treated with protocol-based preoperative radiotherapy followed by complete surgical resection. Data from two prospective trials that included preoperative radiotherapy and surgery for patients with radiographically resectable RPS were combined to define long-term relapse rates and survival. Seventy-two patients with intermediate- or high-grade RPS were treated with preoperative radiotherapy (median dose, 45 Gy; range, 18.0-50.4 Gy). Fifty-four patients (75%) had primary RPS, whereas 18 (25%) had recurrent disease. The median tumor size was 15.5 cm. Sixty-four patients completed the planned preoperative radiotherapy; 57 (89%) underwent laparotomy with curative intent, and 54 (95%) had a macroscopically complete (R0 or R1) resection. With a median follow-up of 40.3 months, 28 patients (52%) who received preoperative radiotherapy and underwent a macroscopically complete resection had recurrences. For the 54 patients who underwent R0 or R1 resection after preoperative radiotherapy, the 5-year local recurrence-free, disease-free, and overall survival rates were 60%, 46%, and 61%, respectively. The median overall survival has not been reached (>60 months). Patients with intermediate- or high-grade RPS treated with preoperative radiotherapy plus complete resection had a median survival >60 months. This compares favorably to historical data for similar patients treated with surgery alone.

Neoadjuvant Therapy of Breast Cancer

Primary systemic therapy is defined as the first systemic treatment a patient receives after cancer is diagnosed, and indicates that subsequent therapies are intended. It is also known as preoperative, induction, or neoadjuvant systemic therapy. Because of high tumor regression rates, primary systemic chemotherapy has become part of the standard of multidisciplinary care for patients with locally advanced and inflammatory breast cancer.An expert panel has reviewed all large randomized clinical trials of primary systemic chemotherapy versus adjuvant systemic therapy in operable breast cancer and concluded that both result in equivalent disease-free, local recurrence-free, and overall survival rates when compared head to head. However, the rate of successful breast-conserving surgery is statistically significantly increased in patients who receive primary chemotherapy; thus, primary systemic therapy is a reasonable alternative for patients with operable breast cancer who are deemed to be appropriate candidates for mastectomy but who desire breast-conserving surgery, or for those patients who desire less extensive breast-conserving surgery. The addition of taxanes or trastuzumab to primary systemic chemotherapy results in a significant increase in the overall and complete clinical response rates and in pathologic complete response (pCR) rates.A poor response to primary systemic chemotherapy is a predictor of poor prognosis and of a high risk of recurrence, irrespective of the type of surgery performed. In contrast, a pCR of the tumor or of cytologically documented axillary lymph node disease correlates strongly with both prolonged disease-free survival and overall survival, and occurs in 6–31% of patients, depending on the breast cancer subtype, the particular chemotherapy regimen used, and on the definition of what constitutes a pCR that is used by the particular group. Thus, pCR may be regarded as one major goal of primary systemic chemotherapy. Emerging data suggest that the achievement of pCR is associated with an excellent long-term outcome, regardless of the therapy regimen that results in pCR.If this association of pCR with outcome, regardless of the therapy regimen resulting in pCR, is confirmed, the application of newer gene- or protein-based technologies to predict at diagnosis which patients will achieve pCR in response to various biologic therapies and chemotherapies will have important clinical implications. In addition, the ability of pCR to predict an excellent long-term outcome may, with further study, become routinely applicable to the study of novel anticancer agents in the adjuvant setting, perhaps ultimately allowing us to avoid the need to perform large expensive trials with many years of follow-up.

Angiosarcoma of the scalp treated with curative radiotherapy plus recombinant interleukin-2 immunotherapy

To evaluate the effectiveness of curative radiotherapy (RT) plus recombinant interleukin-2 (rIL-2) immunotherapy regarding the treatment results for angiosarcoma of the scalp. Curative resection of angiosarcoma of the scalp is usually difficult because of the diffuse, clinically undetectable local spread. RT is a rational therapeutic approach, because a wide region of the dermis can be treated, while sparing the underlying normal tissues. Recently, the effectiveness of immunotherapy with rIL-2 has also been reported in the treatment of angiosarcoma of the scalp. The data of 20 patients with angiosarcoma of the scalp treated with curative RT plus rIL-2 immunotherapy between January 1988 and June 2002 were retrospectively analyzed. The total radiation dose was 70.3 +/- 6.9 Gy. The fractions were 2-3 Gy daily, given 5 d/wk. rIL-2 immunotherapy was performed by transcatheter arterial administration in 10 patients, systemic administration in 11 during the course of RT, and intratumoral injection in 10 during and/or after RT; 12 patients received a combination of two. Five patients underwent limited surgery, and concomitant pacilitaxel chemotherapy was also used in 2 patients. The median survival time for overall, local recurrence-free, and distant metastasis-free survival was 36.2, 11.1, and 17.8 months, respectively. Local recurrence developed in 7 patients (35%), 4 of whom also had evidence of distant metastases. An additional 7 patients (35%) developed distant metastases alone. Recurrence within the radiation field was recognized in 2 patients with systemic rIL-2 administration alone (p < 0.05). Arterial or intratumoral administration combined with systemic administration of rIL-2 resulted in better distant metaststasis-free survival rates (p < 0.05). Curative RT plus rIL-2 immunotherapy provided an efficient, effective means of treating angiosarcoma of the scalp. Arterial or intratumoral administration combined with systemic administration of rIL-2 may prolong survival. Additional studies with detailed treatment protocols are recommended.

Clinical outcomes and prognostic factors in 4839 patients treated with external radiotherapy for stage T1-T2 prostate cancer

Clinical outcomes and prognostic factors in 4839 patients treated with external radiotherapy for stage T1-T2 prostate cancer

Survival after proton-beam irradiation of uveal melanomas

PurposeTo evaluate the independent prognostic factors for survival, metastasis, local recurrence, and enucleation in patients who had undergone proton-beam therapy for posterior uveal melanomas. DesignInterventional case series. MethodsIn this retrospective study, 224 consecutive incident cases were treated at the Biomedical Cyclotron Centre (Nice, France) from June 1991 to December 1997. Overall, metastasis-free, local recurrence-free, and enucleation-free survival rates were calculated according to the Kaplan-Meier method using the log-rank test. The multivariate prognostic analysis was performed using the Cox proportional hazards model. ResultsThe 5-year overall survival rate was 78.1% (SE: 3.7%). A largest basal tumor diameter (LTD) below 10 mm and female sex were independently associated with a better prognosis. The 5-year metastasis-free survival rate was 75.6% (SE: 3.6%). Only an LTD above 10 mm and ciliary body involvement were independently associated with metastasis. Ten patients (4.5%) had a local recurrence, which was correlated with the risk of metastasis (P = .045). The 5-year enucleation-free survival rate was 69.6% (SE: 4.0%). Once again, an LTD below 10 mm and female sex were predictive of a better prognosis. ConclusionOur results with proton-beam therapy correspond to those reported in the literature. This treatment strategy is safe and yields predictably good results. In addition to the two independent prognostic factors for survival and metastasis, namely LTD and ciliary body involvement, sex also had a significant impact in our case series, but the clinical relevance of this finding is unknown.

Skp2 protein expression in soft tissue sarcomas.

p45 S phase kinase-associated protein-2 (p45(skp2)), a member of the F-box family of proteins, is an important component of the Skp1-Cullin-F-box protein (SCF) ubiquitin-ligase complex (SCF(skp2)). The latter has been implicated in the ubiquitination and degradation of p27(kip1) (p27) and G(1)-S cell cycle progression. The expression and prognostic role of Skp2 in a large series of soft tissue sarcomas has not been previously investigated. Clinicopathologic features and immunohistochemical expression of Skp2, p27, and Ki-67 proteins were studied in 182 cases of soft tissue sarcomas (American Joint Committee on Cancer stages II and III). Survival analyses were performed using the Kaplan-Meier method and the Cox regression model. The male to female ratio was 1.2:1, and the median age at the diagnosis was 53 years. The tumors were predominantly located in the lower extremities (n = 163; 90%) and had a median size of 9 cm. High Skp2 expression (> or = 10% of the cells) was identified in 68 tumors (37%), and was correlated with high grade histology (P =.002) and Ki-67 proliferative index (r = 0.44; P <.0001), but not with p27 expression (r = -0.02; P =.80). By univariate analysis, high Skp2 expression was associated with decreased metastasis-free, disease-free, and overall survival. In a multivariate model, high Skp2 expression was an independent predictor for decreased local recurrence-free, disease-free, and overall survival. These results indicate that Skp2 expression is associated with cell proliferation and a worse prognosis in soft tissue sarcomas. The lack of an inverse correlation between Skp2 and p27 suggests that additional molecular events associated with either Skp2 expression or p27 proteolysis may be operating in these tumors.

Matched comparison of radical nephrectomy vs. nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney.

Objective: To report the long-term follow-up of a matched comparison of radical nephrectomy (RN) and nephron-sparing surgery (NSS) in patients with single unilateral renal cell carcinoma (RCC) and a normal contralateral kidney. Patients and Methods: Between August 1966 and March 1999, 1492 and 189 patients with unilateral RCC and a normal contralateral kidney underwent RN and NSS, respectively. Patients with renal impairment, previous nephrectomy, bilateral or multiple RCCs, metastasis, and familial cancer syndromes were excluded. A total 164 patients in each cohort were matched according to pathological grade, pathological T stage, size of tumor, age, sex, and year of surgery. The Kaplan-Meier method and stratified Cox proportional hazards model were used to estimate and compare overall, cancer-specific, local recurrence-free, and metastasis-free survival and survival free of chronic renal insufficiency. The 2 groups were evaluated for early (⩽30 days) complications and proteinuria at last follow-up. Results: At last follow-up, 126 RN patients (77%) and 130 NSS patients (79%) were alive with no evidence of disease. There was no significant difference observed between patients who had RN and those who had NSS with respect to overall survival (risk ratio, 0.96; 95% confidence interval [CI], 0.52–1.74; P = .88) or cancer-specific survival (risk ratio, 1.33; 95% CI, 0.30–5.95; P = .71). At 10 years, similar rates of contralateral recurrence (0.9% for RN vs 1% for NSS) and metastasis (4.9% for RN vs 4.3% for NSS) were seen in each group, whereas the rate of ipsilateral local recurrence for patients who underwent RN and NSS was 0.8% and 5.4%, respectively ( P = .18). There was no significant difference in the early complications between the RN and NSS groups. However, patients who underwent RN had a significantly higher risk for proteinuria as defined by a protein/osmolality ratio of 0.12 or higher (55.2% vs 34.5%; P = .01). At 10 years, the cumulative incidence of chronic renal insufficiency (creatinine > 2.0 mg/dL at least 30 days after surgery) was 22.4% and 11.6%, respectively, for the RN and NSS groups (risk ratio, 3.7; 95% CI, 1.2–11.2; P = .01). Conclusions: This retrospective study of patients with unilateral RCC and a normal contralateral kidney suggests that NSS is as effective as RN for the treatment of RCC on long-term follow-up. The increased risk of chronic renal insufficiency and proteinuria after RN supports use of NSS. Commentary Data from several studies have shown that nephron-sparing surgery (NSS) and radical nephrectomy provide equally effective curative treatment for patients with a single, small (⩽ 4 cm), unilateral, localized renal cell carcinoma (RCC) and a normal opposite kidney [1,2]. A recent study from Memorial Sloan Kettering reported a 10-year cancer free survival rate of 97% following elective partial nephrectomy in 70 such patients [3]. Other studies have further shown that the cost of NSS is equivalent to that of radical nephrectomy [4] and that quality of life is improved following NSS in this setting [5]. Notwithstanding the above data, there has been controversy concerning the renal functional advantage of performing NSS when the contralateral kidney is anatomically and functionally normal. Long-term follow-up after live donor nephrectomy operations has failed to demonstrate any significant adverse sequela in terms of proteinuria, hypertension or renal failure. However, patients undergoing surgical treatment for localized RCC represent a different population who are generally older and often have co-morbid medical conditions. This is the likely explanation for the findings in this important study from the Mayo Clinic which suggest an increased risk of chronic renal insufficiency and proteinuria after radical nephrectomy (compared to NSS) in patients with a normal contralateral kidney. A similar observation was recently reported in a study from Memorial Sloan Kettering presented at the 2001 annual AUA meeting. These emerging beneficial renal functional data enhance the argument in favor of elective NSS in patients with a solitary small (⩽ 4 cm) RCC and a normal contralateral kidney. Andrew C. Novick, M.D.

Matched Comparison of Radical Nephrectomy vs Nephron-Sparing Surgery in Patients With Unilateral Renal Cell Carcinoma and a Normal Contralateral Kidney

To report the long-term follow-up of a matched comparison of radical nephrectomy (RN) and nephron-sparing surgery (NSS) in patients with single unilateral renal cell carcinoma (RCC) and a normal contralateral kidney. Between August 1966 and March 1999, 1492 and 189 patients with unilateral RCC and a normal contralateral kidney underwent RN and NSS, respectively. Patients with renal impairment, previous nephrectomy, bilateral or multiple RCCs, metastasis, and familial cancer syndromes were excluded. A total 164 patients in each cohort were matched according to pathological grade, pathological T stage, size of tumor, age, sex, and year of surgery. The Kaplan-Meier method and stratified Cox proportional hazards model were used to estimate and compare overall, cancer-specific, local recurrence-free, and metastasis-free survival and survival free of chronic renal insufficiency. The 2 groups were evaluated for early (< or = 30 days) complications and proteinuria at last follow-up. At last follow-up, 126 RN patients (77%) and 130 NSS patients (79%) were alive with no evidence of disease. There was no significant difference observed between patients who had RN and those who had NSS with respect to overall survival (risk ratio, 0.96; 95% confidence interval [CI], 0.52-1.74; P = .88) or cancer-specific survival (risk ratio, 1.33; 95% CI, 0.30-5.95; P = .71). At 10 years, similar rates of contralateral recurrence (0.9% for RN vs 1% for NSS) and metastasis (4.9% for RN vs 4.3% for NSS) were seen in each group, whereas the rate of ipsilateral local recurrence for patients who underwent RN and NSS was 0.8% and 5.4%, respectively (P = .18). There was no significant difference in the early complications between the RN and NSS groups. However, patients who underwent RN had a significantly higher risk for proteinuria as defined by a protein/osmolality ratio of 0.12 or higher (55.2% vs 34.5%; P = .01). At 10 years, the cumulative incidence of chronic renal insufficiency (creatinine > 2.0 mg/dL at least 30 days after surgery) was 22.4% and 11.6%, respectively, for the RN and NSS groups (risk ratio, 3.7; 95% CI, 1.2-11.2; P = .01). This retrospective study of patients with unilateral RCC and a normal contralateral kidney suggests that NSS is as effective as RN for the treatment of RCC on long-term follow-up. The increased risk of chronic renal insufficiency and proteinuria after RN supports use of NSS.

Management and Extended Outcome of Patients With Synchronous Bilateral Solid Renal Neoplasms in the Absence of von Hippel-Lindau Disease

To gain information regarding long-term follow-up in patients with synchronous bilateral solid renal neoplasms in whom renal-preserving surgery is imperative. We examined our surgical experience and the survival outcome, as evaluated by Kaplan-Meier and log-rank analysis, of 94 patients (64 men and 30 women) who presented to the Mayo Clinic in Rochester, Minn, from 1973 to 1998 with bilateral synchronous solid renal neoplasms in the absence of von Hippel-Lindau disease. Follow-up of these patients ranged from 1 to 25 years, with a mean of 5.86 years and a median of 4.18 years. Tumors were staged according to the TNM classification. Pathologic staging and grading were usually performed on the kidney with the most extensive cancer. The Cox proportional hazards model was used to assess the relationship of grade (1-4), tumor size, and enucleation as opposed to extended (1 cm) partial nephrectomy on overall, cancer-specific, local recurrence-free, and metastasis-free survival. Seventy-one patients (76%) had bilateral synchronous renal cell carcinoma, and 14 patients (15%) had a unilateral renal cell carcinoma with a contralateral benign solid neoplasm. Nine patients (10%) had bilateral benign solid lesions. Sixty-six patients (70%) underwent a single procedure, whereas 28 (30%) underwent staged surgical procedures. Fifty-one patients (54%) are alive, and 43 (46%) have died. Twenty patients (21%) died of metastatic disease, and 5 (5%) had a local recurrence. Cancer-specific survival of the 85 patients with at least 1 renal cell carcinoma still under observation was 81% (+/- 4.9% SE) and 59% (+/- 8.1% SE) at 5 and 10 years, respectively, and survival to local recurrence was 96% (+/- 2.6% SE) at 5 years and 93% (+/- 3.7% SE) at 10 years with 14 patients still under observation. Grade 3 was a statistically significant factor for metastasis (P < .001). A significant difference in metastasis-free survival and cancer-specific survival was noted dependent on pathologic T stage (P < .001 and P = .02, respectively), with patients with local pT3 disease having a higher rate of metastasis and cancer-specific death. Multivariate analysis revealed that tumor grade was associated with metastasis-free survival (P = .002) and tumor size with cancer-specific survival (P = .04). There was no statistical significance on survival outcome end points according to procedure performed, i.e., enucleation vs extended partial nephrectomy. Long-term results of renal-preserving procedures for a series of patients with bilateral solid renal neoplasms indicate that grade, stage, and tumor size are significant predictors of outcome. Mean follow-up of over 5 years supports nephron-sparing techniques in selected patients because local recurrence was infrequent compared with distant metastasis.

Radiation Therapy in Localized Prostate Cancer: Long-term Results and Late Toxicity

This study was performed to determine the long-term results of radiotherapy in localized prostate cancer. The frequency and severity of late gastrointestinal and genitourinary toxicities were also investigated. Between 1980 and 1991, 206 men with localized prostate cancer were treated with radiotherapy alone at our hospital. Biopsy, transurethral resection of the prostate, or both, confirmed the diagnosis.Overall survival, cancer-specific survival, disease-free survival, local recurrence-free survival and metastasis-free survival were determined and compared with age, stage, grade and diagnostic intervention. A change in treatment policy occurred in 1987. The treatment results of the two periods are compared. Late toxicity was registered according to the Radiation Therapy Oncology Group scale.The 8-year overall survival rates were 60%, 44% and 29% for Stages T1, T2 and T3 respectively (P=0.028). The 8-year cancer-specific survival rates were 86%, 66% and 34% for Stages T1, T2 and T3 respectively (P=0.002). Transurethral resection of the prostate had a negative influence on cancer-free and disease-free survivals, owing especially to an increased incidence of metastases.In the bladder and rectum, late toxicity of grade 2 or more occurred in 26 (13%) of the 199 patients who were alive at 6 months after radiotherapy. One of these patients developed late toxicity 5 years after the radiotherapy. Radiation dose and field size had no detectable influence on the development of late toxicity. The difference between overall survival and cancer-specific survival confirms that many of these patients die without any clinical signs of prostate cancer or metastases. This observation puts a question mark over whether a biochemical end-point alone is of clinical relevance. Although not statistically significant, local recurrence-free, disease-free and cancer-specific free survivals from 1987 onwards improved for larger tumours, which was most likely due to the administration of higher doses of radiation.

Long-term outcome of patients with American Joint Committee on Cancer stage IIB extremity soft tissue sarcomas.

It has been suggested that patients with small (< 5 cm), high-grade extremity soft tissue sarcomas (STS) have an excellent overall prognosis and, consequently, may not require adjuvant therapies. A comprehensive review of all patients with extremity STS treated at a tertiary care cancer hospital over a 9-year period (January 1984 to December 1992) was performed. Prognostic factors, treatment data, and long-term outcome were evaluated in the subset of 111 patients with American Joint Committee on Cancer stage IIB (G3/4, T1a/b) disease. The median tumor size was 3.0 cm (range, 0.6 to 4.9 cm), and 55 tumors (50%) were deep in location. All patients underwent surgical resection; 68 (61%) received pre- or postoperative radiotherapy, and 32 (29%) received doxorubicin-based chemotherapy. The median follow-up was 76 months. Forty patients (36%) experienced 59 recurrences. First recurrences occurred at local, regional, and distant sites in 21, five, and 14 patients, respectively. The 5-year actuarial local recurrence-free, distant recurrence-free, disease-free, and overall survival rates were 82%, 83%, 68%, and 83%, respectively. The presence of a microscopically positive surgical margin was an independent adverse prognostic factor for both local recurrence (relative risk [RR] = 3.75; 95% confidence interval [CI], 1.25 to 11.25; P =.02) and disease-free survival (RR = 2.57; 95% CI, 1.33 to 4.98; P =.005). Event-free outcome for this subset of patients with high-grade STS does not seem as favorable as previously reported by other investigators. Patients who undergo maximal surgical resection with microscopically positive margins represent a subset of T1 STS patients who warrant consideration for adjuvant therapies.