Treatment Recommendations for Urological Symptoms in Cancer Patients: Clinical Guidelines from the Japanese Society for Palliative Medicine.

BACKGROUND: Urological symptoms such as gross hematuria, lower and upper urinary tract symptoms, and bladder pain are common in and distressing for patients with advanced cancer. Although palliation of urological symptoms is important to improve the quality of life of cancer patients and their families and caregivers, clinical guidelines for managing urological symptoms in patients with cancer have not been published. METHODS: Following the formal guideline development process, the Japanese Society for Palliative Medicine (JSPM) developed comprehensive clinical guidelines for the management of urological symptoms in patients with cancer. RESULTS: This article summarizes the recommendations and their rationales and provides a short summary of the development process of the JSPM urological symptom management guidelines. We established five recommendations, all of which were based on the best available evidence and expert consensus. CONCLUSION: JSPM released the first edition of the "Clinical Guidelines for Urological Symptoms in Cancer Patients." Future clinical research and continuous guideline updates are required to improve the quality of managing urological symptoms in patients with cancer.

Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer.

BACKGROUND: A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC). METHODS: Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m(2) on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days. RESULTS: The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1-93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia. CONCLUSIONS: The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity.

Clinical outcome and prognostic factors of sorafenib in Japanese patients with advanced renal cell carcinoma in general clinical practice.

OBJECTIVE: Effects of sorafenib in general clinical practice, especially those with patients of Asian ethnicity, have been rarely investigated. We assessed efficacy, safety and prognostic factors for progression-free survival in Japanese patients receiving sorafenib for advanced renal cell carcinoma. METHODS: We performed a retrospective analysis of 159 Japanese patients with renal cell carcinoma. Progression-free survival was estimated by the Kaplan-Meier method. Objective response (per Response Evaluation Criteria in Solid Tumors) and safety were assessed. Cox proportional hazards model was used to identify independent prognostic factors for progression-free survival. RESULTS: The median progression-free survival was 9.0 months (95% confidence interval, 7.5-10.6 months). In 142 patients with measurable lesions, the objective response rate was 21.8%, and disease control was achieved in 85 (59.9%) patients. Adverse events of any grade occurred in 152 patients (95.6%). Most common adverse events causing discontinuation or interruption of sorafenib were hand-foot skin reaction (22%), rash (10.7%) and liver dysfunction (10.7%). Dose reduction or therapy interruption due to adverse events was required in 128 patients (80.5%). Univariate and multivariate analysis revealed that favorable prognosis according to Memorial Sloan-Kettering Cancer Center prognostic factors and relative dose intensity during the first month of treatment of ≥50% were significant factors for predicting superior progression-free survival with sorafenib treatment. CONCLUSIONS: Sorafenib was effective in Japanese patients with advanced renal cell carcinoma in general clinical practice and was tolerated although most patients required dose reduction or interruption of therapy. Future studies should establish new strategies for treatment without sacrificing both efficacy and patient quality of life.

[An unusual case of cystic nephroma protruding into the renal pelvis].

Cystic nephroma is a relatively rare and benign renal lesion of uncertain etiology. Approximately 200 cases have been described, but only a few cases of cystic nephroma with prominent renal pelvis involvement have been reported. Here, we report an unusual case of cystic nephroma that protruded into the renal pelvis. A 45-year-old woman hospitalized because of a right renal mass detected on clinical examination. The diagnosis of a malignant or benign lesion was not clear. A right nephroureterectomy was performed. The characteristics of the resected specimen were consistent with those of cystic nephroma. Macroscopic examination revealed that the giant lesion originated from the upper renal pelvis and extended into the renal pelvis. The patient is currently free from disease at eight months after the surgery. In general, this tumor arises from the renal parenchyma. To our knowledge, this is the fifth case report on cystic nephroma with prominent renal pelvis involvement.

[Malignant paraganglioma responsive to CVD therapy and radiation therapy : a case report].

The patient, a 55-year-old man, had undergone surgery for retroperitoneal paraganglioma at the age of 45. In February 2006, he visited our hospital with the chief complaint of metastatic tumors detected by a thorough checkup. Computed tomographic (CT) scan revealed a large tumor in the right kidney hilar region and a left supraclavicular lymphadenopathy. Histopathological and immunohistochemical findings of the biopsy specimen taken from the left supraclavicular lymph node led to the diagnosis of recurrent malignant paraganglioma. 123I-MIBG scintigram showed no radioisotope accumulation consistent with the tumor. From April 2006 to September 2006, he received 8 cycles of CVD therapy (cyclophosphamide, vincristine, and dacarbazine). The tumor temporarily responded and was reduced to one-third in size, but soon it became resistant to CVD therapy. In March 2007, because the tumor had begun to grow, he received the 9th course of CVD therapy, but the tumor response was PD. Subsequently, palliative radiation therapy of 50 Gy in 25 fractions was administered and was temporarily effective. The CVD therapy and radiation therapy were considered to be effective for this case. In May 2008, he died 25 months after the start of CVD therapy.

Surveillance following orchiectomy for stage I testicular seminoma: long-term outcome.

OBJECTIVES: To report the long-term outcome of surveillance for stage I seminoma at a single institution in Japan. METHODS: A retrospective review of medical records of 64 patients who underwent orchiectomy between January 1982 and December 2005 was carried out. All of them were managed by surveillance for stage I seminoma. RESULTS: Median follow-up time was 123.8 months. Of the 64 patients, seven developed relapse. Four relapses occurred within the first year after orchiectomy, but three occurred over 4 years after orchiectomy. The actuarial relapse-free rates at 5, 10, and 15 years were 92.1%, 90.0%, and 86.0%, respectively. All patients received salvage chemotherapy at relapse. Four of these seven patients were alive without evidence of disease. One patient died of seminoma and one was alive with this disease. The remaining one patient died of leukemia without secondary relapse of seminoma. T classification was a statistically significant (P = 0.028) risk factor for relapse on univariate analysis. In T1 patients, relapse-free rates at 5, 10, and 15 years were all 97.1%, whereas in T2/T3 patients the corresponding relapse-free rates were 86.4%, 82.1%, and 71.8%, respectively. CONCLUSIONS: The relapse-free rate in the present study was similar to previous reports. Late relapse should be considered during surveillance.

[Rectourethral fistula after radical retropubic prostatectomy: a case report].

The patient, a 56-year-old man, had surgery for anal fistula at the age of 28. In August 2007, he underwent a radical retropubic prostatectomy (RRP) for prostate cancer. Rectal injury was not recognized during the operation. However, on the 8th postoperative day, fecaluria appeared, and rectourethral fistula was diagnosed. We attempted conservative therapy including diverting colostomy and continued drainage using a urethral catheter. Subsequently, the fistula closed spontaneously 3 months after RRP. Eight months after RRP, we performed a transanal repair of rectal mucosa based on the rectal wall advancement flap procedure. The postoperative course was uneventful, and the colostomy was closed in July 2008. By April 2009, he had normal voiding and full anal continence without fistula recurrence.

Prospective evaluation of selection criteria for active surveillance in Japanese patients with stage T1cN0M0 prostate cancer.

OBJECTIVE: Selection criteria for active surveillance (AS) program of localized prostate cancer remain to be standardized. The purpose was to evaluate the validity of selection criteria and investigate the feasibility of this AS program. METHODS: Patients meeting the criteria (i) stage T1cN0M0, (ii) age 50-80, (iii) serum prostate-specific antigen (PSA) 2y', which was defined as the proportion of patients who showed PSADT assessed at 6 months >2 years out of all the patients who chose AS. Point estimate of '%PSADT > 2y' was expected to be >80%. RESULTS: One hundred and eighteen patients opted for AS and 16 chose immediate treatment at enrollment. PSADT for the initial 6 months based on four measurements could be assessed in 106 patients. Intent-to-treat analysis of '%PSADT > 2y' was 71.2% (84/118, 95% CI: 62.1-79.2). Pathological progression rate at 1-year re-biopsy was 33%. Fifty-four (46%) patients remained on AS for maximal observation of 54 months. General health-related QOL in patients undergoing AS was not impaired. CONCLUSIONS: The primary endpoint, '%PSADT > 2y', did not meet the pre-specified decision criteria. Further prospective study with revised program and endpoint is needed.

[Prostatic hypertrophy and prostate cancer].

Synthetic steroidal hormone has been used as the antiandrogens for prostatic hypertrophy, and prostate cancer. In prostate cancer, antiandrogens are defined as substances which prevent androgens from expressing their activity at target sites and divided into steroidal and nonsteroidal antiandrogens. Steroidal antiandrogens have negative feedback inhibition of the hypothalamus, resulting the low plasma concentration of testosterone. Nonsteroidal antiandrogens have antiandrogenic effect in both hypothalamus and target tissues, negative feedback is inhibited and the plasma concentration of testosterone is high. Antiandrogen is generally used with LH-RHa for the neoadjuvant or adjuvant hormonal therapy of surgery and irradiation which is named maximam androgen blockade.

Reduction of irradiation volume and toxicities with 3-D radiotherapy planning over conventional radiotherapy for prostate cancer treated with long-term hormonal therapy.

BACKGROUND: As hormonal therapy has an influence not only on outcome but also on toxicities, we compare the efficacy of three-dimensional radiotherapy planning (3D-RTP) and of conventional radiotherapy (Conv-RT) in association with long-term hormonal therapy in reducing toxicity of treatment. PATIENTS AND METHODS: A retrospective case-control study was performed comparing the frequency of radiation toxicity between 63 Conv-RT and 52 3D-RTP patients with locally advanced prostate cancer (intermediate to high risk) treated with combined hormonal therapy. The average duration of neoadjuvant treatment was 7 months (1-38 months) and that of adjuvant treatment was 38 months (4-94 months). Patients were treated with 70 Gy of box field radiotherapy for the same clinical target volume (60 Gy prostate + seminal vesicle and 10 Gy boost to prostate). RESULTS: Treatment volumes (= X(RL) x Y(SI) x X(AP), where X(RL) = right left length of anterior-posterior portals, X(AP) = anterior posterior length of lateral portals and Y(SI) = superior inferior length of anterior-posterior portals) were significantly smaller in the 3D-RTP group (630 +/- 130 cm3) than in the Conv-RT group (1036 +/- 223 cm3) (p < 0.0001). Acute side-effects in urological tracts (GU) were associated with XRL (p = 0.02), Y(SI) (p = 0.008) and treatment technique (Conv-RT vs. 3D-RTP: p = 0.01). The frequency of acute gastrointestinal tract (GI) toxicity was associated with X(RL) (p = 0.02), X(AP) (p = 0.03). Late GU toxicities were associated with YAP (p = 0.02) and X(RL) (p = 0.03). Treatment technique was the determinant of late GI toxicities (p = 0.03). Frequency of late GI toxicities of G2 or more was reduced from 35% in the Conv-RT group to 15% in the 3D-RTP group (p = 0.03, odds ratio = 0.43). Patients with late GI toxicity received longer periods (39 +/- 19 months) of adjuvant hormonal therapy than the patients without (31 +/- 18 months, p = 0.04). Prostate-specific antigen (PSA) failure-free survival rates at 3 years were 92% for the 3D-RTP group and 90% for the Conv-RT group (73% at 5 years, 67% at 10 years). Overall survival rates were 97% (3-year), 91% (5-year), and 91% (10-year) in the Conv-RT group, compared to 100% at 3 years in the 3D-RTP group. CONCLUSION: Long-term hormonal therapy has the potential to improve outcome but induce late GI toxicity. 3D-RTP simultaneously reduced treatment volume and frequency of acute urinary and late GI toxicities even with long-term hormonal therapy.

[Renal lymphangioma: report of a case].

Renal lymphangioma is a very rare benign tumor caused by failure in the development of the lymphatic communication system. Since December 1997, a 55-year-old man with chronic B-type virus hepatitis has been followed at our hospital. Neither kidney showed any sign of cysts at that time. In November 2000, ultrasound sonography showed a right renal simple cyst measuring 1.0 cm in diameter. Thereafter, the initial cyst increased to 5.5 cm and numerous right renal cysts, appearing similar to multilocular renal cysts, were detected in December 2004. Computed tomography demonstrated a right renal multilocular cystic tumor, 5.5 cm in diameter, which was enhanced by contrast medium. Radical nephrectomy was performed, and the pathological diagnosis was renal lymphangioma based on positive staining with D2-40 antibody, which is reactive to endothelial cells of the lymphatics.

Imaging characteristics of papillary renal cell carcinoma by computed tomography scan and magnetic resonance imaging.

AIM: To analyse the differences in the patterns between clear and papillary renal cell carcinomas using magnetic resonance imaging (MRI) and dual-phase helical computed tomography (CT). METHODS: We examined seven patients with papillary renal cell carcinoma, and six with clear cell carcinoma. The highest attenuation value of tumors in the corticomedullary phase (CMP) and the excretory phase (EP) was measured using the observer-defined region of interest (ROI). MRI consisted of T1-weighted and T2-weighted spin-echo imaging. RESULTS: All five tumors except for one with papillary renal cell carcinoma showed homogenous hypointensity, but all six tumors with clear cell carcinoma showed heterogeneous hyperintensity on their T2-weighted images. In the CMP, the mean CT numbers of the papillary renal cell carcinomas were significantly lower than those of the clear cell carcinomas. The mean enhancement of the papillary renal cell carcinomas in the CMP and the EP was significantly lower than that of the clear renal cell carcinomas. The mean CT numbers of the clear cell carcinomas in the CMP were markedly increased from those on the unenhanced CT; those in the EP were decreased gradually. But the mean CT numbers of the papillary renal cell carcinomas in the EP were still slightly more increased than those in the CMP. The enhancement patterns of the papillary renal cell carcinomas in the CMP and the EP were homogenous, but those of the clear cell carcinomas were heterogeneous. CONCLUSIONS: We can speculate the differential diagnosis from clear to papillary renal cell carcinoma using MRI and dual-phase helical CT.

[Watchful waiting for elderly patients with localized prostate cancer].

Watchful-waiting policy is an important treatment option for some patients with localized prostate cancer and it is widely recognized in Western countries in which the prostate cancer mortality rate is 510 fold higher than that in Japan. Most men with well and perhaps moderately differentiated prostate cancer who have a life expectancy of less than 10 years will die of other causes and it is not clear whether early primary hormone therapy improves survival and the quality of life compared to androgen suppression deferred until signs and symptoms of clinical progression. There is one major question as to whether patients who do not need radical treatment should undergo early primary hormone therapy in Japan in spite of high cost and treatment-related adverse effects of hormone therapy.

[Two cases of femoral nerve palsy after radical prostatectomy].

We report two cases of femoral nerve palsy after radical prostatectomy due to compression ascribed to the use of a ring retractor. The first case is in a 69-year-old man who fell when getting out of bed on the first postoperative day. Physical examination revealed hypoesthesia around the patella and weakness of the quadriceps muscle. The second case is in a 66-year-old man who complained of numbness of the anteromedial aspects of the right thigh and inability to extend his right knee on the first postoperative day. Postoperative femoral nerve palsy is not a well-recognized complication in urology. The literature was reviewed and the management of postoperative femoral nerve palsy was discussed.

[Small cell carcinoma of the kidney: a case report].

A 79-year-old man presented in August 2002 with right flank pain, anorexia, and gross hematuria. Physical examination was significant for a palpable, nontender, firm, and fixed mass in the epigastric region. Computed tomography scan of abdomen revealed a 15 cm tumor occupying almost the whole right kidney with extension into the inferior vena cava. The para-aortic and retroperitoneal lymph nodes were significantly enlarged. Examinations including bone scintigram and chest X-ray revealed no metastases. The patient underwent a ultrasound sonography-guided biopsy of the renal tumor, which showed a small cell carcinoma pathologically, and immunohistochemically. The patient received palliative treatment, and died in February 2003. We reviewed 25 cases including our case, and analyzed the clinical outcome of small cell carcinoma of the kidney.

Failure to maintain the suppressed level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer.

A 75-year-old man with metastatic prostate cancer had been treated with goserelin acetate, and prostate specific antigen (PSA) had decreased, but 11/2 years after beginning the treatment of goserelin acetate, PSA was markedly elevated and serum testosterone was at normal level. After castration the serum testosterone was at castrate level and PSA decreased. In the present case, leuprorelin acetate 1-month depot suppressed the luteinizing hormone level in 1 month, even after the patient underwent castration.

Renal angiomyolipoma with minimal fat.

We report here two patients with angiomyolipoma with minimal fat, who were treated by radical nephrectomy, with a diagnosis of renal cell carcinoma. The tumors in these two patients were hyperattenuated on unenhanced computed tomography (CT) images, but did not show fat components, and were moderately enhanced on contrast-enhanced CT images. The tumor in one patient was homogeneously hypointense on T2-weighted magnetic resonance (MR) images, enhanced during the early phase on dynamic MR images, and, further, showed abundant pulsatile blood vessels on color Doppler examination. These imaging findings of renal tumors suggested the possibility of angiomyolipoma with minimal fat; accordingly, when imaging results suggest this possibility, further careful sampling to identify minimal fat components must be performed by thin-section unenhanced CT.

Stage specific follow-up strategy after cystectomy for carcinoma of the bladder.

BACKGROUND: Follow-up strategies after cystectomy for carcinoma of the bladder should be determined according to the risk of recurrence, which is stage dependent. We aimed to develop follow-up protocol for monitoring patients with carcinoma of the bladder for tumor recurrence and diverted urinary tract complications after radical cystectomy. METHODS: The records of 351 patients with carcinoma of the bladder who underwent cystectomy between 1979 and 1999 were reviewed for dates and presenting symptoms of local and distant recurrences. The results of imaging studies and blood tests were also reviewed. Based on the division of patients into pathological stages of pT1 and lower, pT2, and pT3 and higher groups, we proposed a new follow-up schedule for carcinoma of the bladder. RESULTS: The risk of metastasis was related to the pathological stage of the primary tumor. Recurrence developed in 10 of 124 patients (8%) with pT1 or lower, 17 of 101 patients (17%) with pT2, and 55 of 101 patients (54%) with pT3 or higher disease at a median of 11 (range 6-186), 10 (1-40) and 7 (1-76) months, respectively. Recurrences in patients with pT3 or higher were found earlier and more frequently than those with pT2 or lower. Of 82 patients with metastases, 54 initially were symptomatic, and three of pT1 or lower, six of pT2, and 19 of pT3 or higher were asymptomatic. Based on these results we proposed a stage specific follow-up protocol. CONCLUSIONS: A stage-driven follow-up strategy for monitoring patients after radical cystectomy can reduce medical expenses while efficiently detecting recurrences and complications.

Ipsilateral adrenal involvement from renal cell carcinoma: retrospective study of the predictive value of computed tomography.

OBJECTIVES: To compare the radiologic evidence of adrenal involvement on computed tomography (CT) with pathologic reports and to assess the accuracy of CT in the diagnosis of adrenal involvement with renal cell carcinoma. METHODS: Between January 1992 and June 2000, we treated 229 patients with renal cell carcinoma. In this study, we retrospectively analyzed 73 patients who had been examined by CT before surgery and had undergone radical nephrectomy, including removal of the ipsilateral adrenal gland. The abnormal integrity of the adrenal glands on CT and the pathologic adrenal involvement of renal cell carcinoma were demonstrated by a radiologist and pathologist, respectively. RESULTS: The blinded review by a radiologist of the CT results of 73 patients with renal cell carcinoma identified a normal appearance of the ipsilateral adrenal gland in 54 patients (74%), none of whom had pathologic evidence of malignant involvement. The adrenal gland was diagnosed as abnormal on CT in 19 patients (26%), including enlargement in 7 patients, nodule formation in 7, and an irregular surface in 8. Two of these 19 patients had adrenal involvement. Both were staged at T3M1, and their primary tumors were large, measuring more than 10 cm. In this study, CT demonstrated 100% sensitivity, 76% specificity, 11% positive predictive value, and 100% negative predictive value for ipsilateral adrenal involvement of renal cell carcinoma. CONCLUSIONS: Normal adrenal images on CT could exclude adrenal involvement by renal cell carcinoma. However, radical nephrectomy, including removal of the ipsilateral adrenal gland, should be performed in patients with large tumors.