Sentinel lymph-node biopsy in patients with squamous cell carcinoma of the penis.

OBJECTIVES: To evaluate a single-centre experience with sentinel lymph-node biopsy (SLNB) as a staging procedure in patients with squamous cell carcinoma (SCC) of the penis. PATIENTS AND METHODS: The study included 60 patients with SCC of the penis, who had SLNB in all groins where no palpable nodes were found, and in groins with palpable nodes with negative fine-needle aspiration cytology. Lymphoscintigraphy and intraoperative lymph node detection was done using (99m)Tc-nanocolloid and no use of blue dye. RESULTS: In all, there were 97 SLNB procedures in 52 patients; 20 (20.6%) of the SLNB were positive for nodal metastases. Two negative SLNB proved to be false-negative during the observation period. The false negative-rate was 9%, the sensitivity 91% and the negative predictive value 97.5%. Minor early complications occurred after 4% of the SLNB procedures. No major or late complications were recorded. CONCLUSIONS: SLNB is minimally invasive and can be used as a safe and reliable staging procedure in patients with SCC of the penis. Thus standard lymph-node dissection can be avoided in most patients.

Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma.

PURPOSE: We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 121 consecutive patients who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX [CA IX]) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated. RESULTS: The intratumoral neutrophils ranged from zero to 289 cells/mm(2) tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX < or = 85%. In multivariate analysis, the presence of intratumoral neutrophils (hazard ratio [HR], 3.0; 95% CI, 1.7 to 5.4; P < .0001), pT stage T3b/T4 (HR, 2.1; 95% CI, 1.2 to 3.6; P = .007), and low hemoglobin (HR, 1.8; 95% CI, 1.0 to 3.1; P = .03) were independent prognostic factors significantly associated with short recurrence-free survival. The presence of intratumoral neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P < .0001) and overall survival (HR, 3.1; 95% CI, 1.9 to 5.0; P < .0001). Applying the prognostic value of intratumoral neutrophils to the Leibovich low-/intermediate-risk group (n = 78) showed a 5-year recurrence-free survival of 53% (95% CI, 34.6% to 71.8%; presence of intratumoral neutrophils) versus 87% (95% CI, 77.8% to 96.8%; absence of intratumoral neutrophils). The estimated concordance index was 0.74 using the Leibovich risk score and 0.80 when intratumoral neutrophils were added. CONCLUSION: The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC.

Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5.

OBJECTIVE: To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP; Estradurin) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events. MATERIAL AND METHODS: In total, 910 eligible patients with T0-4, NX, M1, G1-3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or flutamide (Eulexin) 250 mg t.i.d. per os in combination with either triptorelin (Decapeptyl) 3.75 mg i.m. per month or on an optional basis bilateral orchidectomy. RESULTS: At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001). CONCLUSIONS: PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis.

Complications and neobladder function of the Hautmann orthotopic ileal neobladder.

OBJECTIVE: To report the complications and function of the Hautmann orthotopic ileal neobladder . PATIENTS AND METHODS: In a 6.5-year period, 67 patients had an ileal neobladder constructed after radical cystectomy as treatment for invasive carcinoma of the bladder. All complications were reported systematically. Neobladder function was assessed by patient interviews, uroflowmetry and cystometric analyses. RESULTS: There were early complications in 41 patients (61%), and late complications in 32 (48%); 23 (34%) had both early and late complications and 17 (25%) had none. Eighteen of the patients (27%) required a re-operation for complications. At the 4-month follow-up, 90% were continent during the day and 65% during the night; at 1 year after surgery 95% were continent during the day and 73% during the night. The functional bladder capacity and maximum cystometric capacity were close to the natural bladder volume (median 450 and 480 mL, respectively). CONCLUSIONS: Despite the high rate of complications in this study, most were considered as minor and could be treated by conservative or minimally invasive methods. The neobladder had an acceptable resemblance to the native bladder in capacity and function. Consequently the ileal neobladder might be preferred as a urinary diversion after radical cystectomy, if no contraindications are present.

Focal S100A4 protein expression is an independent predictor of development of metastatic disease in cystectomized bladder cancer patients.

OBJECTIVE: The prognosis of patients with apparently localized, operable, muscle-invasive bladder cancer depends to a large extent on the presence or absence of subclinical, microscopic distant metastases at the time of surgery. Expression of the S100A4 protein has been shown to correlate with the risk of metastasis in both animal tumour-model systems and clinical investigations in other tumour types. The purpose of the present study was to investigate the prognostic potential of S100A4 protein expression for predicting distant metastatic relapse in muscle-invasive bladder cancer. METHODS: We analyzed 108 consecutive patients, treated for transitional cell bladder cancer with preoperative radiotherapy and cystectomy. Pretherapeutic biopsies of the bladder tumours were investigated for immunohistochemical expression of S100A4 protein and results, along with clinical and histopathological data, compared with the pattern of relapses over a 10+ yr follow-up period. RESULTS: Focal S100A4 protein expression emerged as the only significant independent predictor of distant metastatic relapse and distant metastasis-free survival in multivariate analysis. CONCLUSION: There is a potential role for this marker in denoting patients with high or low risk of distant relapse independent of clinical stage and grade.

Prognostic factors, pattern of recurrence and survival in a Danish bladder cancer cohort treated with radical cystectomy.

A cohort of 248 consecutive patients with bladder cancer undergoing radical cystectomy between 1992 and 98 was retrospectively followed from diagnosis until death. Prognostic factors, pattern of recurrence and survival were analysed. Pathological T and N, angiolymphatic and perineural invasion had an independent prognostic influence on survival. Patients without muscle-invasive tumour (Ta, T1) had a good prognosis, whereas patients with primarily superficial tumour progressing to muscle-invasive tumour had a significantly poorer outcome. Forty-six percent of these patients developed recurrences in the follow-up period, with a median time from recurrence to death of 5 months. The 5-year disease-specific survival for all 248 patients was 57%. Patients with pT4b or N + all died within 3 years. Patients with positive lymph nodes or T4b were not curable with cystectomy alone. Patients with advanced T or with perineural/vessel invasion are in need of improved treatment options. Patients with superficial tumours at high risk of progression should be offered early cystectomy.

Early and late treatment-related morbidity following radical cystectomy.

OBJECTIVE: To evaluate treatment-related morbidity following cystectomy in a cohort of consecutive bladder cancer patients. The impact of age, comorbid condition, previous pelvic radiotherapy and type of urinary diversion was analysed. MATERIAL AND METHODS: Between 1992 and 1998 the treatment-related early (<30 days after cystectomy) and late morbidity was recorded in 268 consecutive bladder cancer patients (median age 65 years) undergoing cystectomy and the following types of urinary diversion: ileal conduit, n = 195; orthotopic neobladder, n = 36; continent reservoir, n = 33; and ureterocutaneous diversion, n = 4. Twenty-four patients had received previous pelvic radiotherapy and 79 had pre-existing morbidity. The median follow-up period was 5.4 years. RESULTS: The postoperative mortality rate was 2%. Age >70 years and pre-existing morbidity (especially cardiovascular disease) significantly increased the mortality rate. No relationship was found between early complication (57%) and re-exploration rates (17%) and either age, previous radiotherapy, pre-existing morbidity or type of urinary diversion. Patients undergoing orthotopic neobladder or continent reservoir had a significantly increased risk of calculus formation as well as cystectomy-related surgical procedures compared to patients undergoing ileal conduit. Age had a significant impact on vitamin B12 deficiency and renal deterioration, whereas previous pelvic irradiation significantly increased the probability of ureteroenteric stricture and lost renal function. Age and urinary diversion had no impact on hernia, ureteroenteric stricture or pyelonephritis. CONCLUSION: The risk of treatment-related morbidity was high and careful patient selection before cystectomy seems important. The lack of standard criteria regarding how to report morbidity makes comparison with other studies difficult.

Pseudosarcomatous fibromyxoid tumor of the prostate.

A very rare case of benign infravesical obstruction due to a pseudosarcomatous fibromyxoid tumor of the prostate is presented. This entity is clinically and histologically difficult to distinguish from a malignant lesion. A discussion of the histopathological features and a review of the literature is given.

Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours.

This prospective, randomized study based on two associated trials was designed to evaluate the effect of neoadjuvant chemotherapy with cisplatin and methotrexate with folinic acid rescue or no chemotherapy prior to local treatment in patients with T2-T4b, NX-3, MO transitional cell carcinoma of the bladder. In the first trial, local treatment consisted of cystectomy (DAVECA 8901) and in the other trial the treatment was radiotherapy (DAVECA 8902); 153 eligible patients were randomized. The majority of the patients (89%) completed the protocol. The overall time to progression for all 153 patients was 12.9 months. Median time to progression was 14.2 months with chemotherapy and 11.4 months without chemotherapy. The actuarial 5-year overall survival rate for all 153 patients was 29%, and 29% for both treatment groups. Multivariate analyses showed that T-stage, tumour size and serum creatinine were independent prognostic factors for survival. The cystectomy trial included 33 patients. Median survival was 78.9 months, 82.5 months with chemotherapy and 45.8 months without chemotherapy (p = 0.76). The radiotherapy trial included 120 patients. The median survival was 17.6 months. Median survival was 19.2 months in the group receiving chemotherapy and 16.3 in the group not receiving chemotherapy. The 5-year survival rate was 19% in the group receiving chemotherapy and 24% in the groups not receiving chemotherapy (p = 0.98). Late toxicity grade 3 or 4 of the bladder was recorded in 25% of the patients (actuarial rate). Neoadjuvant chemotherapy with cisplatin and methotrexate did not significantly improve disease-free or overall survival in 153 randomized patients with invasive bladder cancer.