Postoperative Radiotherapy Group Research Articles

A Comparison of Treatment Outcomes by Radiochemotherapy and Postoperative Radiotherapy in Locally Advanced Squamous Cell Carcinomas of Head and Neck

To investigate the treatment outcomes by concomitant radiochemotherapy (CHEMORAD), and by surgery and postoperative radiotherapy (PORT) in patients with locally advanced head and neck cancers. A retrospective study included all patients with Stage III and IV (except T1-2 N1) diseases between 1989 and 2002 treated with CHEMORAD (163 patients) or PORT (424 patients) at the L'Hôtel-Dieu de Québec. Chemotherapy was realized with Cisplatin (DDP) 100 mg/m(2), d1, d23, and d45 during radiotherapy or weekly DDP 40 mg/m(2) for 6 weeks in case of patients with poor general condition. Neck dissection was performed if residual disease was diagnosed on CHEMORAD. For the PORT group, 410 patients had neck dissection before adjuvant treatment. The 2-year loco-regional control was 82% for CHEMORAD, and 72% for PORT (P = 0.01). The 2-year disease-free survival was 72% for CHEMORAD, and 64% for PORT (P = 0.02). The results were further confirmed by a Cox proportional hazard model. The results indicated that CHEMORAD is a better approach than PORT in the management of locally advanced head and neck cancers. Further randomized study will be needed to compare radical CHEMORAD with surgery plus adjuvant CHEMORAD to determine an appropriate treatment in the management of locally advanced head and neck squamous cell carcinomas.

Proximal Esophageal Stenosis in Head and Neck Cancer Patients after Total Laryngectomy and Radiation

Background: There has been an increasing focus on late functional effects of head and neck cancer (HNC) treatment. This study was undertaken to evaluate the incidence of late proximal esophageal stricture in patients undergoing total laryngectomy (TL) and radiation therapy (RT). Material and Methods: An institutional retrospective review of HNC patients treated between 1995 and 2003 with TL and RT was undertaken. Thirty-three patients with stage II–IV disease were included; 25 patients had TL and postoperative RT (group 1), while 8 patients had definitive RT with salvage laryngectomy (group 2). Results: The median follow-up was 28 months. At the last follow-up, 25 patients (76%) were alive and disease free. Four had died and 3 developed distant metastasis. Dysphagia or stenosis developed in 40% in group 1 and 75% in group 2 patients. The median time to dysphagia was 5.5 months for all patients. Conclusions: The incidence of esophageal stenosis was 33% for all patients. Contributing factors for esophageal stenosis after TL and RT include continued alcohol and tobacco use, the dose-volume relationship of the RT and normal tissue damage from the tumor and the treatment.

Postoperative radiotherapy for patients with completely resected pathological stage IIIA-N2 non-small cell lung cancer: focusing on an effect of the number of mediastinal lymph node stations involved

Postoperative radiotherapy (PORT), especially using modern technology, for patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. We retrospectively investigated 112 patients with stage IIIA-N2 NSCLC who underwent complete resection of the lung tumor in our institution from 1986 through 2003. Among the 91 patients determined suitable candidates for PORT postoperatively, 45 patients received PORT (PORT group) and 46 did not (non-PORT group). We analyzed the correlation between PORT use and clinicopathological characteristics, number of involved mediastinal lymph node stations, recurrence, and survival. Five-year and 10-year survival rates of PORT group were 53.2% and 40.0%, which were superior, however, not statistically different, to those (39.3% and 27.5%) of non-PORT group (P=0.6284). According to the number of mediastinal lymph node stations, PORT was more effective for multiple station metastasis than single station metastasis. The disease-free survival of PORT group was significantly better than that of non-PORT group among the patients with multiple station metastasis. Five-year disease-free survival rate of PORT group and non-PORT group were 41% and 5.9%, respectively (P=0.0220). PORT using modern techniques can reduce local recurrence and improve overall survival especially for patients with multiple station N2. Prospective randomized control trials are warranted.

Acute Toxicity in Definitive Versus Postprostatectomy Image-Guided Radiotherapy for Prostate Cancer

To assess the incidence of acute gastrointestinal (GI) and genitourinary (GU) injury and the dose-volume response in patients with clinically localized prostate cancer treated with image-guided radiotherapy using helical tomotherapy. Between November 2004 and March 2007, 146 consecutive patients with localized prostate cancer were treated with helical tomotherapy at the City of Hope Medical Center. Of the 146 patients, 70 had undergone prostatectomy. Acute GI and GU toxicities were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Cancer of Medical scoring system. Events were scored for patients developing Grade 2 or greater morbidity within 90 days after the end of radiotherapy (RT). The dosimetric parameters included the minimal dose received by the highest 10%, 20%, 50%, 80%, and 90% of the target volume, the mean rectal dose, minimal rectal dose, maximal rectal dose, and the volume receiving > or =45, > or =65, and > or =70 Gy. These variables, plus the status of radical prostatectomy, hormonal therapy, RT techniques, and medical conditions, were included in a multivariate logistic regression analysis. A goodness-of-fit evaluation was done using the Hosmer-Lemeshow statistic. A dose-response function for acute GI toxicity was elicited. The acute GI Grade 2 or greater toxicity was lower in the definitive RT group than in the postoperative RT group (25% vs. 41%, p <0.05). Acute GU Grade 2 or greater toxicity was comparable between the two groups. No grade 3 or greater complications were observed. No dosimetric variable was significant for GU toxicity. For acute GI toxicity, the significant dosimetric parameters were the minimal dose received by 10%, 20%, and 50% of the target volume and the mean rectal dose; the most predictive parameter was the minimal dose received by 10% of the target volume. The dose-modifying factor was 1.2 for radical prostatectomy. The results of our study have shown that acute rectal symptoms are dose-volume related. Postprostatectomy RT resulted in a greater incidence of acute GI toxicity than did definitive RT. For postoperative RT, it would be prudent to use different dose-volume limits.

Résultats préliminaires de l'essai EORTC 22911 : prostatectomie radicale suivie ou non de radiothérapie postopératoire dans les cancers de la prostate à haut risque de récidive

Purpose Local failure after radiotherapy can arise with cancer extending beyond the capsule and/or involvement of seminal vesicles or positive surgical margins. Methodology After undergoing radical prostatectomy 1005 patients were randomly assigned (1999–2001) to a wait and see policy or an immediate postoperative irradiation (60 Gy delivered over 6 weeks); eligible patients had pN0 M0 tumors and one or more pathological risk factors mentioned above. The main end-point was 5-year biochemical progression free survival. Results After a median follow-up of 5-year biochemical progression free survival was significantly improved in the irradiated group (74%, 98% CI: 68.7–79.3 vs 52.6%, 98% CI: 46.6–58.5; P < 0.0001) Clinical progression free survival was also significantly improved ( P < 0.0009). The cumulative rate of loco-regional failure was also significantly improved ( P < 0.0009). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group ( P = 0.0005), but severe toxicity (grade 3 or higher) were rare with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group ( P = 0.07). Conclusion Immediate external irradiation after radical prostatectomy improves biochemical progression free survival and local control in patients with positive surgical margin or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the impact on overall survival.

A controlled prospective randomized trial of adjuvant chemoradiotherapy following radical cystectomy in advanced high risk bladder cancer

5082 Background: High risk locally advanced bladder cancer patients experienced low survival rates, high local recurrence and high rate of distant metastasis. Postoperative radiotherapy (PORT) improved local control and survival, yet it did not affect distant metastasis. Methods: A prospective randomized trial was performed at NCI, Cairo, Egypt including 146 patients in 2 arms. Patients who underwent radical cystectomy and pelvic lymphadenectomy had to have one or more of the following: stage P3b or P4a, G3 or involved lymphadenopathy. Arm I (74 patients) received PORT 45 Gy/30 fractions/3 weeks. Arm II (72 patients) received 2 courses of adjuvant chemotherapy (Gemcitabine 1 gm/m2 D1 and D8 and cisplatin 70 mg/m2 D2), same PORT regimen followed by another 2 courses of Gemcitabine-cisplatin. Results: Chemotherapy and radiation were tolerated with grade 1/2 toxicities. Delayed toxicity was comparable in both arms. The 45-month DFS was 51 ± 12 % in the whole group. This was affected significantly by performance status (p = 0.0001), pathological stage (p = 0.0099), nodal involvement (p = 0.004) and number of risk factors (p = 0.16). Though there was improvement of 45-month DFS from 28 ± 20% in PORT group to 70 ± 6 % in chemoradiotherapy group, yet it did not reach to the level of statistical significance (p = 0.18). Patients having one risk factor, G3 or no nodal involvement in arm II experienced better DFS than those in arm I (p = 0.17, 0.11 and 0.17 respectively). Distant metastasis-free survival (DMF) rate increased with the addition of chemotherapy from 29±21% to 75±6%. This effect was intensified in patients having one risk factor, grade 3 and negative nodes. Conclusions: Adjuvant chemoradiotherapy using Gemcitabine-cisplatin and PORT was tolerable. There was DFS improvement and higher DMF rates with the addition of chemotherapy to PORT (not statistically significant yet). Patients with one risk factor, G3 or no nodal involvement seemed to benefit more from the added chemotherapy. No significant financial relationships to disclose.

Immediate postoperative radiotherapy in residual nonfunctioning pituitary adenoma: Beneficial effect on local control without additional negative impact on pituitary function and life expectancy

To demonstrate the benefit of immediate postoperative radiotherapy in residual nonfunctioning pituitary adenoma (NFA) in perspective to the need for hormonal substitution and life expectancy. Retrospective cohort analysis of 122 patients, operated for NFA between 1979 and 1998. Recurrence was defined as regrowth on computed tomography or magnetic resonance imaging. The occurrence of hormonal deficiencies was defined as the starting date of hormonal substitution therapy. Seventy-six patients had residual NFA after surgery and received immediate postoperative radiotherapy (Group 1); three patients developed a recurrence, resulting in a 95% local control rate at 10 years. Twenty-eight patients had residual NFA after surgery, but were followed by a wait-and-see policy (Group 2). Sixteen developed a recurrence, resulting in a local control rate of 49% at 5 years and 22% at 10 years (p < 0.001 compared with Group 1). There were no differences between Group 1 and 2 regarding the need for substitution with thyroid hormone, glucocorticoids, and sex hormones before first surgery, directly after surgery and at end of follow-up. There were no differences in hormone substitution free survival between Group 1 and Group 2 during the study period after first surgery. Life expectancy was similar in Group 1 and 2, and their median life expectancy did not differ from median life expectancy in the general population. Immediate postoperative radiotherapy provides a marked improvement of local control among patients with residual NFA compared with surgery alone, without an additional deleterious effect on pituitary function and life expectancy.

Locally Advanced Tonsillar Squamous Cell Carcinoma: Treatment Approach Revisited

The purpose of this study was to review the treatment policy for locally advanced stage III and IV squamous cell carcinoma (SCC) of the tonsil at the Princess Alexandra Hospital Head and Neck Unit, Brisbane, Australia. The records of 148 patients with curable stage III and IV SCC of the tonsil were reviewed from the years 1992 to 2004 inclusive. During this period, patients were treated with surgery and postoperative radiotherapy and only offered definitive radiation if they were medically or surgically inoperable. There were 102 patients treated with surgery +/- postoperative radiotherapy (group 1) and 46 patients treated with definitive radiotherapy +/- chemotherapy (group 2). The endpoints of locoregional control (LRC), disease specific survival (DSS), and overall survival (OS) were studied and prognostic factors were investigated with univariate and multivariate analyses. The 5-year OS, DSS, and LRC were 57%, 69%, and 84%, respectively. Univariate analyses showed that patients in group 1 had a superior OS (69% vs. 41%, P = .007), a trend toward improvement in LRC (88% vs. 73%, P = .08), and a nonsignificant improvement in DSS (75% vs. 56%, P = .14). There was a greater percentage of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 or less in group 1, suggesting selection bias toward the surgical group. Multivariate analyses, which adjusted for known prognostic factors, showed that treatment group was significant for OS but not for LRC or DSS. Surgery and postoperative radiotherapy continues to provide a superior outcome in locally advanced tonsil SCC in patients with surgically resectable disease, good ECOG performance status, and medically operable.

Isolated full-thickness cervical stromal invasion warrants post-hysterectomy pelvic radiotherapy in FIGO stages IB–IIA uterine cervical carcinoma

To evaluate the potential benefit of postoperative radiotherapy (PORT) in women with isolated full-thickness cervical stromal invasion (FTSI) as an unfavorable pathological finding after radical hysterectomy and pelvic lymph node dissection (PLND) in FIGO stages IB-IIA cervical carcinoma. A total of 1868 patients with stages IB-IIA cervical carcinoma underwent radical hysterectomy and PLND between January 1982 and December 2002. Seventy-four of these patients had isolated FTSI without any other unfavorable pathological finding, such as lymph node metastasis, microscopic parametrial involvement, involved resection margin, lympho-vascular space invasion, or large clinical tumor diameter (>4 cm). Forty-one of these patients had no adjuvant treatment (S group) and 33 received PORT (PORT group). Patients with isolated FTSI who received chemotherapy were excluded. Treatment outcomes in the PORT and S groups were compared. Ten-year disease-free survival (DFS) and pelvic-failure-free survival (PFFS) of S group vs. PORT group were 73.2% vs. 92.4% (P=0.038) and 79.8% vs. 97.0% (P=0.044), respectively. According to a Cox proportional hazards model developed by forward, stepwise regression incorporating all prognostic variables, only PORT was marginally significant for DFS (RR 0.234; 95% CI 0.051-1.067; P=0.061) and significant for PFFS (RR 0.055; 95% CI 0.005-0.620; P=0.019). A grade 4 late complication developed in two patients (6%) in PORT group. PORT administered to patients with isolated FTSI after radical hysterectomy and PLND improves pelvic control in FIGO stages IB-IIA cervical carcinoma with acceptable morbidity.

Postoperative radiotherapy after radical prostatectomy: A randomised controlled trial (EORTC trial 22911): Bolla M, van Poppel H, Collette L, van Cangh P, Vekemans K, Da Pozzo L, de Reijke TM, Verbaeys A, Bosset J-F, van Velthoven R, Maréchal J-M, Scalliet P, Haustermans K, Piérart M, European Organization for Research and Treatment of Cancer, Department of Radiation Oncology, Centre Hospitalier Universitaire

Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer. After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat. The median age was 65 years (IQR 61–69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74.0%, 98% CI 68.7–79.3 vs 52.6%, 46.6–58.5; p<0.0001). Clinical progression-free survival was also significantly improved (p=0.0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (p=0.0726). Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival.

Adjuvant chemoradiotherapy after radical cystectomy in advanced high risk bladder cancer: A prospective randomized trial

4545 Background: High risk locally advanced bladder cancer patients experienced low survival rates, high local recurrence and extensive distant metastasis. Postoperative radiotherapy (PORT) though improved the survival through improving local control. Methods: A prospective randomized trial was performed at NCI, Cairo, Egypt including 142 patients in 2 arms. Patients who underwent radical cystectomy and pelvic lymphadenectomy had to have one more of the following: P3b or P4a stage, G3 or involved lymphadenopathy. Arm I (71 patients) received PORT 45 G/30 fractions/3 weeks. Arm II (71 patients) received 2 courses of adjuvant chemotherapy (Gemcitabine 1 gm/m2 D1 and D8 and cisplatin 70 mg/m2 D2), same PORT regimen followed by another 2 courses of Gemcitabine-cisplatin. Results: Chemotherapy was tolerated with grade 1/2 toxicities. Early radiation reactions were also tolerable in both arms, slightly more in arm II. Delayed toxicity was comparable in both arms. The 2-year DFS was 67.6 ± 5.9% in the whole group. This was affected significantly by performance status (p = 0.009), pathological stage (p = 0.001), tumor cell type (p = 0.053), nodal involvement (p = 0.07) and number of risk factors (p = 0.09). Though there was improvement of DFS from 61.5 ± 7.4% in PORT group to 70.9 ± 6.1% in chemoradiotherapy group, yet it was not statistically significant (p = 0.2). Patients having one risk factor, low pathological stage or no nodal involvement in arm II experienced better DFS than those in arm I (p = 0.07, 0.08 and 0.09 respectively). Conclusions: Adjuvant chemoradiotherapy using Gemcitabine-cisplatin and PORT was tolerable with minimal severe toxicities. There was DFS improvement with the addition of chemotherapy to PORT (not statistically significant yet). Patients with one risk factor, lower pathological stage or no nodal involvement seemed to benefit more from added chemotherapy. No significant financial relationships to disclose.

Risk of cardiac (CD) and pulmonary (PD) death after post-operative radiotherapy (PORT) for non-small cell lung cancer (NSCLC): Analysis of the Surveillance, Epidemiology, and End-Results (SEER) program

6122 Background: Since radiation treatment planning and delivery techniques have evolved over time, we investigated if the risk of CD and PD after PORT for NSCLC has decreased. Methods: We selected postoperative patients with non-metastatic NSCLC diagnosed in 1980–1995 from the SEER data. To account for peri-operative mortality, patients with survival less than 6 months were excluded. Variables analyzed included age, gender, laterality, disease stage, SEER geographic region, ethnicity/race, and histology. CD and PD were calculated at 10 years and compared for patients diagnosed during 1980–83, 1984–88, 1989–91, and 1992–95. Cox proportional hazards models (CPHM) were used to calculate the hazard of CD and PD. Results: This analysis included 29,093 patients treated with observation (OB) and 8334 patients who received PORT. For the patients treated with OB, the 10 yr mortality rates for CD/PD were 17%/2%, 15%/3%, 15%/3%, and 14%/&lt;0.1% for years of diagnosis of 1980–83, 1984–88, 1989–91, and 1992–95, respectively. For the patients who were treated with PORT, the 10 yr mortality rates for CD/PD were 21%/3%, 21%/4%, 15%/4%, and 14%/&lt;0.1% for years of diagnosis of 1980–83, 1984–88, 1989–91, and 1992–95, respectively. CPHM showed the hazard of CD for patients treated with OB to be significantly decreasing; 1980–83 (HR=1.412; CI=1.257–1.585; p&lt;0.0001), 1984–88 (HR=1.260; CI=1.124–1.413; p&lt;0.0001), 1989–91 (HR=1.180; CI=1.054–1.321; p=0.0042), and 1992–95 (HR=1.00; Ref.). CPHM showed the hazard of CD for patients who received PORT to be significantly decreasing; 1980–83 (HR=1.568; CI=1.222–2.011; p=0.0004), 1984–88 (HR=1.435; CI=1.125–1.830; p=0.0036), 1989–91 (HR=0.992; CI=0.767–1.282; p=0.9504), and 1992–95 (HR=1.00; Ref.). Although PD showed a similar decreasing trend relative to year of diagnosis, CPHM did not demonstrate this to be statistically significant. Conclusions: There was a greater reduction in the CD rate in the PORT group compared to the OB group. While there appeared to be a trend in the reduction of PD, the results were not significant which may be secondary to too few events occurring. No significant financial relationships to disclose.

Long-Term Benefits of Elective Radiotherapy After Prostatectomy for Patients With Positive Surgical Margins

The benefit of adjuvant radiotherapy after prostatectomy for patients with pathological risk factors but with an undetectable postoperative PSA remains controversial. In this retrospective study we define the benefits of elective postoperative radiotherapy in this setting. A total of 44 patients received elective postoperative radiotherapy at a single institution in the PSA era (1989 to 1995) for positive surgical margins and undetectable postoperative PSA. Radiotherapy was delivered to a median dose of 60 Gy. Clinical target volume included the prostate bed. Pelvic nodes were not treated. The four-field box technique with customized blocking of bladder, rectum and small bowels was used and defined the planning target volume. The patients were then compared to a contemporaneous group of 189 patients with positive surgical margins who underwent radical prostatectomy without any adjuvant therapy. Failure was defined as biochemical (PSA) recurrence and was timed from first detectable PSA. The 5 and 10-year biochemical no evidence of disease was 90.9% and 90.9% for the elective postoperative radiotherapy group, and 66.4% and 54.5% for the observation group, respectively (p = 0.0012). Median time to biochemical failure was also longer in the elective postoperative radiotherapy group (88.6 months) compared to the observation group (43.5 months) (p <0.001). Risk factors for biochemical recurrence on multivariate analysis were Gleason score greater than 7 (p = 0.017), established extracapsular extension (p = 0.002) and lack of elective postoperative radiation (p = 0.001). This is one of the longest followup studies showing that elective postoperative radiation therapy is associated with improved bNED and prolonged time to recurrence. Combined radical prostatectomy and elective postoperative radiotherapy should be considered in the management of high risk prostate cancer, especially in the presence of positive surgical margins despite undetectable PSA.

Radical versus postoperative radiotherapy for localized prostate cancer: a 10-year experience of an academic hospital

This study is a presentation of our department's experience in the treatment of localized prostate cancer with either radical or postoperative radiotherapy (RT). Fifty-five patients with clinical localized prostate cancer were reviewed. Thirty-three patients (T1-T2AN0M0 stage) were treated with radical RT and 22 (T2B-T3N0M0 stage) with postoperative RT. All patients received hormonal therapy. Primary end points of the study were the incidence of clinical and biochemical recurrences and death in the whole group and according to treatment modality. Within a median follow-up of 18 months the overall incidence of clinical relapse was 16.9%, of biochemical relapse 12.7% and of death 10.9%. Both treatment options achieved similar outcomes despite the fact that the patients in the postoperative RT group were of higher stage. Radical RT group tended to have better overall and disease-free survival compared to postoperative RT group, but there was no statistically significant evidence. Long-term toxicity was negligible.

The Value of Postoperative Radiotherapy in Renal Cell Carcinoma: A Single-Institution Experience

To evaluate the efficacy of postoperative irradiation in renal cell carcinoma. Forty patients with localized renal cell carcinoma admitted to our hospital between 1986 and 1999 were evaluated. All patients were initially treated with radical nephrectomy. Postoperative radiotherapy was given to 26 of 40 patients (65%). Fourteen patients (35%) received no adjuvant therapy. Median age was 55 years (range, 20-70 years). Twenty-four patients (60%) were men and 16 patients (40%) were women. Histopathological diagnosis was renal cell carcinoma in all of the patients. N+ disease was present in 3 patients (7%). Stage I and II disease was present in 25 patients (63%) and stage III and IV disease in 15 patients (37%). Two patients (5%) had T1a disease, 11 patients (27%) had T1b, 15 patients (38%) had T2, 11 patients (27%) had T3a and 1 (3%) patient had T3b. In the radiotherapy group, renal bed and regional lymphatic fields were irradiated with daily fractions of 180-200 cGy/fraction to a total dose of 46-50 Gy, using parallel opposing fields. The 5-year overall survival rates were 70% in the postoperative radiotherapy group and 20% in the no adjuvant treatment group, showing no significant difference (P = 0.1). The 5-year disease-free survival rates were 66% in the radiotherapy group and 16% in the no treatment group, with a significant difference in both univariate and multivariate analyses (P = 0.045 and P = 0.0007, respectively). Stage III and IV disease, tumor size 27 cm, presence of distant metastasis and lactate dehydrogenase level > 450 U/L were found to be adverse prognostic factors for overall survival in both univariate and multivariate analyses. Analyzing the factors affecting disease-free survival, absence of postoperative radiotherapy and tumor size > or = 7 cm were found to be adverse prognostic factors in univariate and multivariate analyses. Multi-institutional prospective randomized trials using modern radiotherapy techniques such as conformal radiotherapy and intensity-modulated radiotherapy are necessary to evaluate the real role of radiotherapy and its effect on survival in renal cell carcinoma, especially in selected patients with a high risk of local or regional failure.

Adjuvant Therapy in Rectal Cancer: What is the Truth?

It’s just like deja vu. Japanese surgeons have often been dismissive of the value of adjuvant treatment for gastric cancer reported from Europe and America (1,2) because of differences in the degree of lymph node dissection between Japan and Europe/America (3). In contrast, Japanese surgeons may be surprised and delighted at the results of the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC) of postoperative adjuvant chemotherapy for rectal cancer published in this issue of the JJCO (4), the results of which have not been so exciting for European and American oncologists. Such differences have resulted from attitudes towards the basic surgical procedures and the strategy of postoperative adjuvant treatment for rectal cancer. In Europe and America, adjuvant therapy for rectal cancer has included radiotherapy as a standard. In Japan, postoperative chemotherapy has been the primary treatment mainly because of excellent outcomes of surgery including autonomic nerve-preserving D3 dissection (lateral lymphadenectomy). The latest National Comprehensive Cancer Network (NCCN) guidelines prescribe preoperative concomitant radiotherapy and chemotherapy (FU – LV or Capecitabine) and postoperative chemotherapy (FU – LV or FOLFOX or Capecitabine) or, when preoperative chemoradiotherapy was not given, postoperative concomitant radiotherapy and chemotherapy (FU – LV or FOLFOX or Capecitabine) (5). The use of chemotherapy has been based on the evidence of postoperative adjuvant chemotherapy in colon cancer, not rectal cancer. As for radiotherapy, local recurrence was reduced but the survival rate not increased in most reports. In the USA, postoperative radiotherapy following surgery for rectal cancer has been used from the beginning for local control. A randomized controlled trial of MOF therapy and postoperative adjuvant radiotherapy using surgery alone as the control arm has been performed (NSABP R-01 study). The 5 year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the MOF therapy group. Local control was significantly better in the postoperative adjuvant radiotherapy group, but DFS and OS were not (6). Although these findings did not clarify the significance of postoperative adjuvant radiotherapy, the 1990 NCI Consensus Development Conference defined chemotherapy + postoperative adjuvant radiotherapy as a standard postoperative adjuvant therapy for stage II and III rectal cancer (7). The subsequent NSABP R-02 study concluded that postoperative adjuvant radiotherapy did not improve the prognosis of rectal cancer. This study used the MOF therapy group, which was effective compared with the surgery alone group in the NSABP R-01 study, as the control. It investigated MOF versus MOF + postoperative adjuvant radiotherapy, MOF versus 5-FU/LV, and 5-FU/LV versus 5-FU/LV + postoperative adjuvant radiotherapy. No significant differences were noted in DFS or OS between the groups treated with adjuvant chemotherapy alone and chemotherapy + adjuvant radiotherapy after surgery. Disease free survival was significantly higher in the 5-FU/LV group when compared with MOF, but there was no difference in OS (8). These findings had a great impact on postoperative adjuvant radiotherapy, and the American Society of Clinical Oncology (ASCO) initiated discussion on the role of postoperative adjuvant radiotherapy. A subsequent meta-analysis performed by the Colorectal Cancer Collaboration Group confirmed that postoperative adjuvant radiotherapy significantly reduced local recurrence, but showed no significant difference in OS (9). Since it was clarified that postoperative adjuvant radiotherapy did not improve the prognosis of rectal cancer, the emphasis turned to the role of preoperative adjuvant radiotherapy. Various trials on the role of preperative adjuvant radiotherapy for rectal cancer have been reported, but a final conclusion is not yet reached. Two recent meta-analyses have shown that preoperative adjuvant radiotherapy reduces local recurrence rates by almost 50% and overall mortality by 2–10% (9, 10). Preoperative radiotherapy with higher biologically effective doses (of at least 30 Gy) have shown a larger reduction than either preoperative radiotherapy with lower doses or postoperative radiotherapy. However, the trials included in these meta-analyses all started before the broad introduction of total mesorectal excision (TME) surgery. The only randomized trial of TME with or without preoperative radiotherapy was that conducted by the Dutch Colorectal Cancer Group. After 2 years follow-up the estimated local recurrence rates were 2.4% with preoperative radiotherapy and 8.2% without preoperative radiotherapy. This relative reduction of local control For reprints and all correspondence: Hiroya Takiuchi, Internal Medicine II, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan. E-mail: in2028@poh.osaka-med.ac.jp

Treatment results and prognostic factors in oral tongue cancer: analysis of 80 patients

Treatment results and prognostic factors for 80 patients with oral tongue cancer admitted to Istanbul University Oncology Institute between 1987 and 2000 were retrospectively analysed. The patients were treated by surgery and postoperative or curative radiotherapy. Median age was 55 (22–93) out of which 41 patients (51%) were male and 39 (49%) were female. One patient (1%) had stage I disease, 28 patients (36%) stage II, 18 patients (23%) stage III and 32 patients (40%) stage IVA disease. Nineteen patients (24%) were medically inoperable or refused surgical treatment, so were treated with curative radiotherapy to a total dose of 70 Gy (group A). The remaining 61 patients (76%) were treated with surgery and postoperative external beam radiotherapy (group B). The median follow-up time was 44 months. The 5-year overall and loco-regional disease-free survival rates were 42% and 46%, respectively. The 5-year overall survival rates were 16% in group A and 49% in group B ( P = 0.0002). The 5-year disease-specific survival rate was 23% in group A while in group B it was 49%; the difference was statistically significant ( P = 0.02). Combined treatment improves overall and disease-free survival in patients with stage II, III and IVA oral tongue cancer. In patients who are not candidates for surgery, the effect of radiotherapy may be increased with the use of brachytherapy.

Long-term results of primary adenocarcinoma of the urinary bladder: A report on 192 patients

Objectives To evaluate the clinical presentation and treatment end results of primary adenocarcinoma of the urinary bladder, and to determine the significant independent prognostic factors that determine this outcome. Patients and Methods Of 3659 patients who underwent cystectomy, 192 had adenocarcinoma of the urinary bladder, with a relative frequency of 5.2%. Most of these patients (68.2%) presented in late stages (P3 + P4). The incidence of pelvic lymph nodes involvement was 25.5%. Mucinous adenocarcinoma was reported in 28 patients (14.6%), papillary in 20 (10.4%), signet ring in 14 (7.3%), while not otherwise specified was reported in 130 (67.7%) in the cystectomy specimens. Results Mucinous and signet-ring histologic subtypes showed increased frequency of high stages and high grades, and more nodal involvement than the papillary and not otherwise specified. All patients were treated with radical cystectomy and pelvic lymphadenectomy with (69 patients) or without (123) postoperative radiotherapy. The 5-year disease-free survival rate was 46 ± 4% for all patients with adenocarcinoma. Postoperative radiotherapy improved the disease-free survival significantly. The 5-year disease-free survival rate for the postoperative radiotherapy group was 61 ± 6% compared to 37 ± 5% for the cystectomy alone group ( P = 0.002). Local control rate was significantly improved from 53 ± 7% for cystectomy alone to 96 ± 3% for postoperative radiotherapy patients ( P = 0.00001). Distant metastases were the leading cause of death in the postoperative radiotherapy group. Conclusions Within the limitations provided by retrospective studies, it could be concluded that postoperative radiotherapy improved the disease-free survival through its effect on local control. The disease-free survival independent prognostic variables were tumor stage, postoperative radiotherapy, nodal involvement, and adenocarcinoma subclassification. These factors, except the adeno-subclassification, were also found to determine the local control rate. On the other hand, the independent prognostic factors for distant metastasis were lymph nodal involvement, stage, and adeno-subclassification.

Long-standing complications after treatment for cancer of the uterine cervix-clinical significance of medical examination at 5 years after treatment

The purpose of this study is to investigate the side effect in patients who survived for more than 5 years after initial treatment for invasive cervical cancer. Between January 1984 and December 1997, 341 patients underwent primary treatment for invasive cervical cancer. One hundred nine patients who underwent medical examinations at 5 years after primary treatment were reviewed. The patients were divided into three groups: radical surgery alone (group A), radiotherapy alone (group B), and radical surgery with postoperative radiotherapy (group C). Dysuria was seen in 8%, and positive catheterized urine culture was noted in about 20% of groups A and C. Hydronephrosis was seen in 2% and 9% of groups A and B, respectively. Colitis or ulcer detected by proctosigmoidoscopy was noted in 15%, 50%, and 43% of groups A, B, and C, respectively, frequently observed in radiotherapy group (P= 0.0029). Lymphocyst was still present in 6% of group A, and leg edema was noted in 14%, 6%, and 15% of groups A, B, and C, respectively. Long-standing abnormal findings including urinary and bowel complications were presented in this study. Periodic physical examination after treatment should be performed because complications existed over a long time.

Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911)

Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer. After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat. The median age was 65 years (IQR 61-69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74.0%, 98% CI 68.7-79.3 vs 52.6%, 46.6-58.5; p<0.0001). Clinical progression-free survival was also significantly improved (p=0.0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (p=0.0726). Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival.