W. Meinhardt

Dynamic sentinel node biopsy for penile cancer: reliability of a staging technique

PURPOSE We determine the value of dynamic sentinel node biopsy for staging squamous cell carcinoma of the penis. MATERIALS AND METHODS A total of 90 patients with clinically node negative penile cancer were prospectively entered in this study. Preoperative lymphoscintigraphy was performed after intradermal injection of 99mtechnetium nanocolloid around the primary tumor. The sentinel node was intraoperatively identified with the aid of intradermal administered patent blue dye and a gamma ray detection probe. Histopathological examination of sentinel nodes included serial sectioning and immunohistochemical staining. Regional lymph node dissection was performed only if metastasis was found in a sentinel node. Median followup was 36 months (range 5 to 95). RESULTS Lymphoscintigraphy visualized 217 sentinel nodes in 159 inguinal regions of 88 patients. A total of 208 sentinel nodes were intraoperatively identified in 149 inguinal regions of 88 patients. Sentinel node metastasis was found in 19 inguinal regions of 18 patients. Four of 8 patients with unilateral clinical stage N1 disease had a tumor positive sentinel node on the opposite site. Regional recurrence after excision of a tumor negative sentinel node or after nonvisualization was seen in 5 patients, resulting in a false-negative rate of 22% (5 of 23). The 3-year disease specific survival was 98% and 71% for patients with a tumor negative or tumor positive sentinel node, respectively (p = 0.0018). CONCLUSIONS Occult lymph node metastases in penile cancer can be detected with a sensitivity of about 80% by dynamic sentinel node biopsy, including preoperative lymphoscintigraphy, vital dye and a gamma ray detection probe.

LASER THERAPY FOR CARCINOMA IN SITU OF THE PENIS

PURPOSE Carcinoma in situ of the penis, also referred to as Bowens disease or erythroplasia of Queyrat, may lead to invasive squamous cell carcinoma. We assessed the results of laser therapy for carcinoma in situ of the penis. MATERIALS AND METHODS From 1986 to 2000 we treated 19 patients with carcinoma in situ of the penis with the neodymium:YAG or carbon dioxide laser. Treatment was assessed retrospectively. No patient was lost to followup. RESULTS No complications developed and cosmesis was excellent. After 2 to 4 months 3 patients (16%) received repeat treatment because of incomplete disappearance of the lesion. Mean followup was 32 months. True carcinoma in situ recurrent in 5 patients (26%) at an average followup of 25 months (range 6 to 75), while 1 had infiltrating carcinoma. All patients with carcinoma in situ underwent repeat laser treatment. CONCLUSIONS In our experience laser therapy is appropriate initial treatment for carcinoma in situ of the penis with excellent cosmetic and functional results. This therapy is also suited for recurrence without the need for more mutilating therapy. However, the high incidence of recurrence indicates the need for careful followup and patient self-examination.

Value of SPECT/CT for Detection and Anatomic Localization of Sentinel Lymph Nodes Before Laparoscopic Sentinel Node Lymphadenectomy in Prostate Carcinoma

Laparoscopic evaluation of sentinel nodes is useful for staging prostate cancer, but preoperative localization of deep abdominal sentinel nodes with planar lymphoscintigraphy is difficult. We evaluated the value of SPECT/CT for detecting and localizing sentinel nodes in prostate cancer. Methods: 99mTc-nanocolloid was injected peri- and intratumorally, guided by transrectal ultrasonography, in 46 patients with prostate cancer of intermediate prognosis. Patients underwent planar imaging after 15 min and 2 h, SPECT/CT after 2 h, and laparoscopic sentinel node lymphadenectomy on the same day. SPECT was fused with CT and analyzed using 2-dimensional orthogonal slicing and 3-dimensional volume rendering. We evaluated the number of extra sentinel nodes found by SPECT/CT, the number of sentinel nodes found by SPECT/CT outside the area of the extended pelvic lymphadenectomy, and the anatomic information provided by SPECT/CT. Furthermore, we classified the value of the additional SPECT/CT images into 3 categories (no advantage, presumable advantage, and definite advantage) according to the extra anatomic information given and whether additional sentinel nodes were found by SPECT/CT. Results: The patients had a mean age of 64 y (range, 53–74 y) and received a mean injected dose of 218 MBq (range, 147–286 MBq). The sentinel node visualization rate was 91% (42 patients) for planar imaging and 98% (45 patients) for SPECT/CT. In 29 of the 46 patients (63%), SPECT/CT revealed additional sentinel nodes (especially lymph nodes near the injection area) not seen on planar imaging. In 7 patients, those additional sentinel nodes were positive for metastasis (being the exclusive metastatic sentinel node in 4 patients). Overall, 15 patients (33%) had positive sentinel nodes. Sentinel nodes outside the area of extended pelvic lymphadenectomy were found in 16 patients (35%), whereas in 56% of these patients those nodes were not seen on planar imaging. Performing SPECT/CT had no advantage in 13% of the patients, a presumable advantage in 24%, and a definite advantage in 63%. Urologic surgeons used the SPECT/CT images to guide their trocar insertion sites and sentinel node finding with the probe. Conclusion: More sentinel nodes can be detected with SPECT/CT than with planar imaging alone. In comparison with planar imaging, SPECT/CT especially reveals extra sentinel nodes near the prostate and outside the area of the extended pelvic lymphadenectomy. Furthermore, the modality provides useful additional information about the anatomic location of sentinel nodes within and outside the pelvic area, leading to improved intraoperative sentinel node identification.

Cognitive complaints and cognitive impairment following BEP chemotherapy in patients with testicular cancer

Introduction. There is growing concern that some cytotoxic regimens for cancer affect cognitive functioning. This study examined the prevalence of cognitive complaints and deficits in testicular cancer (TC) patients treated with the worldwide standard BEP (bleomycin, etoposide and cisplatin) chemotherapy. Materials and methods. Seventy TC patients treated with BEP chemotherapy after surgery (S+CT) were examined with interviews and neuropsychological tests. These patients were compared with 57 TC patients treated with radiotherapy after surgery (S+RT) and with 55 TC patients that received surgery only (S). Patients were examined a median of 3 years after completion of treatment. Results. Thirty two percent of the S+CT patients reported cognitive complaints compared with 32% of the S+RT patients and 27% of the S patients (p=0.85). No differences in mean cognitive test performance were observed between the groups. On individual impairment scores, more S+CT patients showed cognitive dysfunction compared with S patients, but not compared with S+RT patients (S+CT versus S [p=0.038, OR=4.6, CI=1.1–19.7], S+CT versus S+RT [p=0.70, OR=0.8, CI=0.3–2.4] and S+RT versus S [p=0.070, OR=3.7, CI=0.8–15.7). Cognitive complaints were not related to cognitive test performance, but to emotional distress and fatigue. Discussion. Cognitive complaints are common among TC patients, independent of treatment modality. These complaints are related to emotional distress and fatigue and not to formal cognitive deficits. The finding of a small group of TC patients treated with chemotherapy exhibiting cognitive deficits should be confirmed in a prospective study before we can decide on its cause and relevance.

Contemporary management of regional nodes in penile cancer-improvement of survival?

PURPOSE The management of regional nodes of penile squamous cell carcinoma has changed with time due to improved knowledge about diagnosis and treatment. To determine whether changes in the treatment of regional nodes have improved survival, we compared contemporary 5-year cancer specific survival of patients with squamous cell carcinoma of the penis with that of patients in previous cohorts. MATERIALS AND METHODS In an observational cohort study of 1,000 patients treated during 56 years 944 were eligible for analysis. Tumors were staged according to the 2009 TNM classification, and patients were divided into 4 cohorts of 1956 to 1987, 1988 to 1993, 1994 to 2000 and 2001 to 2012, reflecting changes in clinical practice regarding regional nodes. Kaplan-Meier survival curves with the log rank test and Cox proportional hazards modeling were used to examine trends in 5-year cancer specific survival. RESULTS The 5-year cancer specific survival of patients with cN0 disease treated between 2001 and 2012 was 92% compared to 89% (1994 to 2000), 78% (1988 to 1993) and 85% (1956 to 1987). The 5-year cancer specific survival improved significantly since 1994, the year dynamic sentinel node biopsy was introduced, at 91% (1994 to 2012) vs 82% (1956 to 1993) (p = 0.021). This conclusion still holds after adjustment for pathological T stage and grade of differentiation (HR 2.46, p = 0.01). Extranodal extension, number of tumor positive nodes and pelvic involvement in node positive (pN+) cases were associated with worse 5-year cancer specific survival. CONCLUSIONS Despite less surgery being performed on regional nodes, 5-year cancer specific survival has improved in patients with cN0 disease. The number of tumor positive nodes, extranodal extension and pelvic involvement were highly associated with worse cancer specific survival in patients with pN+ disease. In this group other treatment strategies are needed as no improvement was observed.

SURVEILLANCE CAN BE THE STANDARD OF CARE FOR STAGE I NONSEMINOMATOUS TESTICULAR TUMORS AND EVEN HIGH RISK PATIENTS

PURPOSE We investigate the results of a surveillance program for stage I nonseminomatous germ cell tumors to validate a surveillance policy, and furthermore improve it by analyzing diagnostic instruments and identifying prognostic factors for relapse. MATERIALS AND METHODS From 1982 to 1994, 90 patients with stage I nonseminomatous germ cell tumors entered a surveillance protocol after orchiectomy. Patients with relapse were treated with cisplatin based chemotherapy. A statistical analysis of possible prognostic factors for relapse was performed. RESULTS Relapse occurred in 23 (26%) patients. Disease specific survival was 98.9%, and 1 patient died of tumor. Most relapses were located in retroperitoneal lymph nodes only (78%). Tumor markers were the most important indicators of relapse. However, in 22% of patients with relapse abdominal x-ray of lymphangiographic contrast showed the first sign of relapse. Computerized tomography located all but 1 relapse. Vascular invasion (p = 0.0001), tumor size (p = 0.0341) and presence of immature teratoma (p = 0.0154) were significantly predictive of relapse with the multivariate analysis, percentage embryonal carcinoma only by univariate analysis (p = 0.032). The relapse rate was highest (52%) when vascular invasion was present. CONCLUSIONS With surveillance for stage I nonseminomatous germ cell tumors, excellent treatment results can be achieved that are comparable to primary retroperitoneal lymph node dissection. Tumor markers and computerized tomography are highly reliable for detecting relapse. Lymphangiography is still of staging value. Pathological factors may influence the choice of adjuvant treatment. However, relapse risks of 50% to 60% are maximally achieved with presently available prognostic factors, and so sparing morbidity of adjuvant treatment by a surveillance protocol remains a feasible option even in these patients.

The role of initial immunotherapy as selection for nephrectomy in patients with metastatic renal cell carcinoma and the primary tumor in situ.

OBJECTIVE A prospective pilot study in patients with metastatic renal cell cancer and the primary in situ to assess the feasibility of immunotherapy prior to nephrectomy and to evaluate the rationale for a future randomized trial to define the role of response to upfront immunotherapy as selection for cytoreductive surgery. PATIENTS AND METHODS Sixteen patients with synchronous multiple metastases were treated with the primary tumor in place and were evaluated with regard to age, sex, sites of extrarenal disease, morbidity, response, nephrectomy rate, time to progression and overall survival. Immunotherapy consisted of 2 courses low-dose IL-2 4MIU/m(2), subcutaneous GM-CSF 2.5 microg/kg and interferon-alpha (IFN-alpha) 5MU flat on day 1-13 and 22-34. Patients with either partial remission (PR) or stable disease (SD) underwent nephrectomy followed by a third and fourth course. RESULTS No response was seen in the primary tumors. With regard to extrarenal sites SD was noted in nine cases, PR in two and progressive disease (PD) in five. Eleven patients underwent nephrectomy. No surgical complete response (CR) could be achieved. All patients with PD died after a median overall survival of 3 months versus 11.5 months (range 4-22) in those who underwent nephrectomy. Four patients are still alive at 10, 12, 18 and 19 months. Median duration of response was 6 months (range 2-10). One patient with SD following nephrectomy developed CR after two additional cycles, which is currently maintained for >10 months. CONCLUSIONS Absence of progression at metastatic sites following immunotherapy may be used as a selection for nephrectomy in this selected group. Non-responding patients can be spared from surgery. A randomized study is needed to assess the timing of nephrectomy in combination with immunotherapy with regard to morbidity, overall survival and quality of life.

Penile sparing surgery for penile cancer-does it affect survival?

PURPOSE Management of squamous cell carcinoma of the penis changed in recent decades in favor of penile sparing surgery. We assessed whether penile sparing therapies were increasingly applied in our penile squamous cell carcinoma cohort with time and whether penile sparing affected 5-year cancer specific survival. MATERIALS AND METHODS We reviewed the records of 1,000 patients treated between 1956 and 2012, of whom 859 with invasive tumors were eligible for analysis. Tumors were staged according to the 2009 TNM classification. Binary logistic regression was used to assess penile preservation vs amputation with time. Cancer specific survival was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards model. Competing risk analysis was done for local recurrence. RESULTS With time significantly fewer penile amputations were performed. The 5-year cumulative incidence of local recurrence as the first event after penile preservation was 27% (95% CI 23-32) while after (partial) penectomy it was 3.8% (95% CI 2.3-6.2, Gray test p <0.0001). Patients treated with penile preservation showed no significant difference in survival compared to patients treated with (partial) amputation after adjusting for relevant covariables. Factors associated with cancer specific survival were pathological T stage, pathological N stage and lymphovascular invasion on multivariable analysis. In the penile preservation group local recurrence as a time dependent variable in a Cox model was not associated with cancer specific survival (HR 0.52, 95% CI 0.21-1.24, p = 0.13). CONCLUSIONS Significantly more penile preservation therapies were performed in more recent years. Although patients treated with penile preservation experienced more local recurrences, 5-year cancer specific survival was not jeopardized.

Sexuality Preserving Cystectomy and Neobladder (SPCN): Functional Results of a Neobladder Anastomosed to the Prostate

OBJECTIVES In order to preserve the sexual functions in patients in need of a cystectomy, a feasibility study has been performed. METHODS In 24 male patients the seminal vesicles and the prostate were left in situ and a Studer type neobladder was anastomosed to the lateral edge of the prostate. RESULTS Storage and voiding strongly resembled the patterns reported in neobladder patients with the anastomosis directly to the urethra. Four of the 24 males needed to perform clean intermittent catheterisation (CIC). All but one patients had daytime continence. Three patients needed a pad at night. Five patients had erectile dysfunction, of whom two responded well to sildenafil treatment, one had good rigiscan measured nightly erectile function and one had poor erections prior to the operation. Half of the patients had antegrade ejaculation, two patients reported sometimes antegrade and sometimes retrograde ejaculation. CONCLUSION This feasibility trial showed that in the majority of our patients the remaining prostate does not interfere with micturition and the sexual functions were preserved.

Laparoscopic Sentinel Lymph Node Biopsy for Prostate Cancer: The Relevance of Locations Outside the Extended Dissection Area

Objective. To assess the relevance of sentinel lymph nodes (SNs) outside the extended pelvic lymph node dissection area (e-PLND). Patients and Methods. Evaluation of our laparoscopic SN procedures for prostate cancer patients of intermediate prognosis. Retrospective data collection on the exact location of the excised SNs and the pathology results were analyzed. Results and Limitations. Of the 121 patients, 49 had positive lymph nodes. 37 patients (31%) had SNs outside the e-PLND template. Five of these nodes were tumor bearing but only twice exclusively so. Of the 14 patients considered for salvage treatment, 6 were node positive. 7 of these 14 patients (50%) had SNs outside the extended dissection area, yet none of these nodes were tumor positive. Limitations are those of a retrospective study. Conclusions. Laparoscopic SN biopsy may show SNs outside the e-PLND template in 31% of the patients. However, nodes that are exclusively positive in one of these areas are rare. For the dichotomy positive or negative nodes, the locations outside the e-PLND area are not often relevant. Nevertheless, when all positive nodes are to be treated by resection or radiotherapy, these locations are relevant. When considering salvage treatment for prostate cancer, the method is feasible.