Development and external validation of a prognostic tool for prediction of cancer-specific mortality after complete loco-regional pathological staging for squamous cell carcinoma of the penis.

OBJECTIVE: To develop a novel postoperative prognostic tool, which attempts to integrate both pathological tumour stage and histopathological factors, for prediction of cancer-specific mortality (CSM) of squamous cell carcinoma of the penis (SCCP). PATIENTS AND METHODS: Patients with SCCP treated with inguinal lymph node dissection (ILND) or sentinel LN biopsy at a single institution were used for nomogram development and internal validation (n = 434), while a second cohort was used for external validation (n = 338). Multivariable Cox proportional hazards were used to examine the prognostic ability of patient age, a modified tumour staging that distinguishes between spongiosum and cavernosum body ingrowth tumours, a modified LN staging that integrates information on presence/absence of LN metastasis, extent of inguinal LN metastases, pelvic LN involvement, and extranodal involvement, and tumour grade. Model performance was quantified using measures of discrimination and calibration. RESULTS: Overall, 36% of patients had positive LN metastases (n = 156). In univariable analyses, the modified tumour and LN staging systems were statistically significantly associated with CSM, and remained in the final model with a discrimination of 89% within internal validation, and 95% within external validation. Calibration was nearly perfect. CONCLUSIONS: The newly developed model integrates important prognostic factors, which existing models do not consider. Its performance was highly accurate using measures of discrimination and calibration.

Quality of life for patients treated for penile cancer.

PURPOSE: We assessed the impact of primary surgery, including penile sparing surgery vs (partial) penectomy and lymphadenectomy, on sexuality and health related quality of life. MATERIALS AND METHODS: We invited 147 patients surgically treated for penile cancer at our institution between 2003 and 2008 to complete the IIEF-15, SF-36®, IOC (version 2) and questions on urinary function. We evaluated the impact of primary surgery type and lymphadenectomy on these outcomes. We also compared patient SF-36 scores with those of an age and gender matched normative sample from the general Dutch population. RESULTS: A total of 90 patients (62%) returned a completed questionnaire. Surgery type and extent were not associated significantly with most of the study outcomes assessed. However, men who underwent (partial) penectomy reported significantly more problems than those treated with penile sparing surgery, including orgasm (effect size 0.54, p = 0.031), appearance concerns (effect size 0.61, p = 0.008), life interference (effect size 0.49, p = 0.032) and urinary function (83% vs 43%, p <0.0001). Men who underwent lymphadenectomy reported significantly more life interference (effect size 0.50, p = 0.037). The patient sample scored significantly better than the normative sample on the SF-36 physical component (p = 0.044) and the bodily pain subscale (p <0.001). CONCLUSIONS: Few differences were observed in sexuality and health related quality of life as a function of primary surgery and lymphadenectomy. However, (partial) penectomy and lymphadenectomy were associated with more problems with orgasm, body image, life interference and urination. Additional longitudinal studies are warranted to evaluate individual changes with time in these outcomes.

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.

The Impact of a Multidisciplinary Tumor Board (MTB) on Treatment Decision Making for Patients With Renal Cell Carcinoma (RCC): 5-Year Data Analysis.

OBJECTIVE: To describe the impact of a multidisciplinary tumor board (MTB) for renal cell carcinoma (RCC) patients in a locoregional renal cancer network by evaluating shared decision making (SDM) and adherence to MTB recommendations. DESIGN, SETTING AND PARTICIPANTS: This prospective cohort study included all cases from a Dutch renal cancer network with suspicion of or histologically confirmed RCC discussed in MTBs between 2017-2022. Main endpoints were distribution of cases presented, proportion of recommendations with multiple treatment options enabling shared decision making (SDM), definite treatment after SDM and adherence to MTB recommendations. Further endpoints were definite treatment per tumor stage stratified by age and inclusion in clinical trials. Outcomes were displayed as means and proportions (%). Pearson's Chi-Squared test was used to analyze the effect of age on definite treatment advice. RESULTS: Overall, 2651 cases were discussed, of which 1900 (72%) were new referrals and 751 (28%) rediscussions. Majority of cases were cT1a-b tumors (46%) and 22% were local recurrences or metachronous metastatic. Adherence to MTB recommendation was 96% and in 30% multiple treatment options were recommended, allowing for SDM. In 45% of cases with cT1a tumors multiple treatment options were recommended by the MTB, resulting in (cryo)ablation (32%) and AS (30%) as most frequent definite treatments after SDM. Among patients with cT3-4 tumors the inclusion rate in clinical trials was 47%. CONCLUSIONS: A network MTB creates opportunity to discuss multiple treatment options and clinical trials in SDM with patients at a high rate of adherence to MTB recommendation.

Indications and Outcomes for Deferred Cytoreductive Nephrectomy Following Immune Checkpoint Inhibitor Combination Therapy: Can Systemic Therapy be Withdrawn in Patients with No Evidence of Disease?

Background: Upfront cytoreductive nephrectomy (CN) is no longer the standard of care for patients with metastastic renal cell carcinoma (mRCC) with intermediate or poor prognosis according to the International mRCC Database Consortium categories. Objective: To investigate indications for CN following first-line ipilimumab-nivolumab, and assess management and outcomes for patients achieving no evidence of disease (NED) after CN. Design setting and participants: This was a retrospective cohort study among 125 patients with synchronous mRCC who received ipilimumab-nivolumab treatment between March 2019 and June 2022 at four European centres. At one of the four centres, nivolumab was stopped following NED. Outcome measurements and statistical analysis: We measured complete response of metastases (mCR) according to Response Evaluation Criteria in Solid Tumours 1.1; near-complete response of mestastases (mnCR) was defined as a >80% reduction in cumulative metastatic volume. Treatment-free survival (TFS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS) were determined. Results and limitations: At median follow-up of 25 mo, 23/125 patients (18%) had undergone deferred CN. Of 26 patients (21%) with mCR or mnCR, 19 (73%) underwent CN to achieve NED, of whom 11 (58%) discontinued nivolumab, with median TFS of 21 mo. For patients who continued (n = 8, 42%) versus discontinued nivolumab following NED, 2-yr DFS was 83% versus 60% (p = 0.675) and 3-yr CSS was 100% versus 70% (p = 0.325). Four patients underwent CN because of a dissociated response of the primary tumour and were still alive at median follow-up of 5 mo. Conclusions: CN can result in NED, durable DFS, and substantial time off systemic therapy. More collaborative data are required to ascertain the benefits of treatment discontinuation versus oncologic safety. Patient summary: In our study using real-world data, 18% of patients treated with immunotherapy underwent deferred kidney surgery. The majority were free of disease after 3 years. Half of the patients who stopped immunotherapy after surgery have been off therapy for 21 months or longer. Larger studies are needed to investigate the effect of kidney surgery and discontinuation of immunotherapy on survival.

F-18 Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography Has High Diagnostic Value for Pelvic and Distant Staging in Patients with High-risk Penile Carcinoma.

BACKGROUND: For penile cancer patients with pelvic metastases, multimodal treatment is advised, but pelvic lymph node metastases are often found upon surgical resection only. Early selection for multimodal treatment requires reliable noninvasive staging. OBJECTIVE: To evaluate the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) for staging pelvic lymph nodes and distant metastases in high-risk penile cancer patients. DESIGN, SETTING, AND PARTICIPANTS: FDG-PET/CT scans performed in patients with clinically overt inguinal lymph node metastases and/or high-risk primary tumors (bulky T3 or T4) were retrospectively analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All scans were reviewed by two independent nuclear medicine physicians staging the pelvic nodes and distant metastases. FDG-PET/CT findings were compared with histology after node dissection if available, or with positive imaging or follow-up of at least 1 yr. RESULTS AND LIMITATIONS: Between 2006 and 2016, 61 patients met the inclusion criteria. For staging of pelvic nodes, sensitivity was 85% (specificity 75%, negative predictive value [NPV] 90%, and positive predictive value [PPV] 65%). For the detection of distant metastases, FDG-PET/CT had a PPV of 93%. Results are limited by the retrospective design and the lack of direct comparison with CT scanning alone. CONCLUSIONS: FDG-PET/CT has high sensitivity and a high NPV for staging of pelvic lymph nodes in high-risk penile cancer. It also has a high PPV for the detection of distant metastases, which were found in 23% of patients. Therefore, FDG-PET/CT enables early selection for multimodal treatment of patients with pelvic metastases and may help avoid futile treatment of patients with distant metastases. PATIENT SUMMARY: We studied whether positron emission tomography with computed tomography (PET/CT) scans in patients with advanced penile cancer can detect metastases before lymph node surgery is done. PET/CT scans can detect or rule out pelvic lymph node metastases, and can detect distant metastases. This helps in making timely treatment decisions (before surgery).

Incidence trends and survival of penile squamous cell carcinoma in the Netherlands.

We examined trends in the incidence and mortality, and described the survival of patients with penile squamous cell carcinoma in the Netherlands between 1989 and 2006. On the basis of nationwide population-based data, 3-year moving average European age-standardized incidence and 10-year relative survival estimates were calculated. Penile squamous cell carcinomas were categorized according to stage grouping based on the TNM classification. In the 17-year study period, 2000 primary penile cancers were diagnosed in the Netherlands of which 1883 (94%) were squamous cell carcinomas. Median age at diagnosis was 68 years. The majority of patients (57%) were diagnosed with localized tumors (Stage 0 or I). The percentage of missing disease characteristics increased with increasing age. The 3-year moving average incidence rate of patients with penile squamous cell carcinoma increased significantly from 1.4 per 100,000 person-years in 1989 to 1.5 in 2006 with an estimated annual percentage of change of 1.3%. Ten-year relative survival of patients according to the different stage groups was 93% for Stage 0, 89% for Stage I, 81% for Stage II, the 9-year survival was 50% for patients with Stage III disease and a 2-year survival of 21% for patients was found for Stage IV disease. Our study shows that the incidence rate of penile squamous cell carcinoma in the Netherlands has increased slightly, especially the incidence of carcinomas in situ. Patients with Stage III and IV tumors have poor survival.

Inguinal recurrence following therapeutic lymphadenectomy for node positive penile carcinoma: outcome and implications for management.

PURPOSE: We investigated the treatment results and outcomes of patients with pathological node positive penile carcinoma who experienced an inguinal recurrence after therapeutic lymphadenectomy, and determined the clinicopathological features predictive of such recurrences. MATERIALS AND METHODS: Data of 161 patients with pN+ penile carcinoma were analyzed. Ipsilateral postoperative radiotherapy was given if histopathology revealed 2 or more metastases and/or extranodal extension. Medium observed followup was 60 months. The 5-year incidence of inguinal recurrence was estimated using a competing risk analysis considering death a competing risk. RESULTS: An inguinal recurrence developed in 26 patients following lymphadenectomy after a median of 5.3 months. The overall estimated 5-year inguinal recurrence rate was 16%. Of the 26 patients with inguinal recurrence ipsilateral adjuvant radiotherapy was indicated in 22 but given in 11. The other 11 patients had recurrence in the groin before the start of adjuvant radiotherapy. Median survival after inguinal recurrence was 4.5 months. Only 2 of 26 patients (8%) underwent successful salvage after inguinal recurrence. Pronounced differences in estimated recurrence rates were found among several clinicopathological variables indicating extensive penile cancer. Patients with 3 or more unilateral metastatic inguinal nodes and/or extranodal extension and/or pelvic nodal involvement defined a subgroup with high risk pN+ penile cancer. CONCLUSIONS: Most inguinal recurrence following therapeutic lymphadenectomy in pN+ penile carcinoma occurs within a short time. Patients experiencing such a recurrence have a poor outcome with limited salvage options. Patients with 3 or more unilateral metastatic inguinal nodes and/or extranodal extension and/or pelvic nodal involvement represent a high risk group that may benefit from multimodality treatment.

Identification of high risk pathological node positive penile carcinoma: value of preoperative computerized tomography imaging.

PURPOSE: Patients with penile carcinoma, and 3 or more histopathologically proven unilateral metastatic inguinal nodes, and/or extranodal extension, and/or pelvic metastasis are considered a subgroup with prognostically unfavorable parameters for disease specific death and local recurrence after inguinal lymphadenectomy. We established radiographic criteria for the preoperative identification of such patients. MATERIALS AND METHODS: Preoperative diagnostic computerized tomography studies of 30 patients with penile carcinoma with proven unilateral or bilateral lymph node metastasis were reviewed independently by 2 radiologists blinded for patient data. All computerized tomography images were analyzed per side (60). Several radiographic criteria were assessed for regional lymph nodes with short-axis diameter 8 mm or greater and/or central nodal necrosis. Sides were characterized as high risk if histopathology revealed 3 or more metastatic inguinal nodes and/or extranodal extension and/or pelvic nodal involvement. RESULTS: Histopathological nodal involvement was found in 38 sides (63%) including 22 sides (37%) defined as high risk. The presence of central nodal necrosis and/or irregular nodal border of the regional lymph nodes on the preoperative computerized tomography identified the high risk subgroup with a sensitivity of 95% (21 of 22) and a specificity of 82% (31 of 38). All 7 sides falsely designated as high risk harbored inguinal metastases but they were classified as low risk. The interobserver agreement of each radiographic parameter was almost perfect. CONCLUSIONS: The presence of central nodal necrosis and/or an irregular nodal border of the regional lymph nodes on preoperative computerized tomography images are accurate and reproducible criteria to identify high risk pathological node positive penile cancer. These criteria can be used for risk stratification and patient counseling.

Prognostic significance of extranodal extension in patients with pathological node positive penile carcinoma.

PURPOSE: We assessed the prognostic significance of extranodal extension, defined as tumor extension through the lymph node capsule into the perinodal fibrous-adipose tissue, as well as several other risk factors in node positive penile cancer cases. MATERIALS AND METHODS: We analyzed prospectively collected data on a consecutive series of 156 chemotherapy naïve patients with proven lymph node involvement who underwent therapeutic regional lymphadenectomy. Postoperative external radiotherapy was indicated when histopathological analysis revealed more tumor than 1 intranodal metastasis. We estimated cancer specific survival using the Kaplan-Meier method. Multivariate analysis was done according to the Cox proportional hazards model of factors statistically significant on univariate analysis. RESULTS: Adjuvant radiotherapy was done in 70 patients (45%). Median followup was 57.8 months. Overall 5-year cancer specific survival was 61%. Men with extranodal extension had significantly decreased 5-year cancer specific survival compared with men without it (42% vs 80%). Other prognostic variables on univariate analysis were bilateral metastatic involvement vs unilateral, 3 or greater unilateral metastatic inguinal nodes vs 2 or fewer, inguinal lymphadenectomy positive margin status vs negative status and pelvic lymph node involvement. Pathological T stage or differentiation grade were not significant predictors of outcome. On multivariate analysis extranodal extension and pelvic lymph node involvement remained associated with decreased cancer specific survival (HR 2.37 and 2.20, respectively). CONCLUSIONS: Metastatic inguinal lymph node extranodal extension and pelvic lymph node involvement are independent predictive parameters of cancer specific survival in patients with pathologically node positive penile carcinoma despite surgery with postoperative radiotherapy.

18F-FDG PET/CT for monitoring induction chemotherapy in patients with primary inoperable penile carcinoma: first clinical results.

PURPOSE: The aim of this study was to explore the role of (18)F-FDG PET/CT for monitoring treatment response in patients with primary inoperable (i.e. advanced) penile carcinoma treated with induction chemotherapy and to compare the metabolic tumour response with the radiological evaluation provided by CT imaging. METHODS: Eight patients with advanced penile carcinoma were studied. All had undergone (18)F-FDG PET/CT imaging at baseline and after two cycles of induction chemotherapy. The metabolic tumour response was evaluated according to European Organisation for Research and Treatment of Cancer (EORTC) criteria for therapy response. The radiologic tumour response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Response evaluations were done separately and blinded for other patient data. For definition of the reference, all patients were rated as responders or non-responders by a multidisciplinary tumour board. RESULTS: PET/CT showed hypermetabolic uptake of FDG matching with malignancy in all eight patients. According to the reference, six patients were responders and two non-responders after two cycles of chemotherapy. The metabolic tumour response was considered accurate in all eight patients. In seven of the eight patients, the radiological tumour response was in agreement. In three patients correctly identified as responders, the radiological tumour response was deemed suboptimal compared with the metabolic assessment. Five of the six responders continued chemotherapy after response evaluation up to four cycles and were operated subsequently. Histopathological analysis confirmed the metabolic tumour response. CONCLUSION: (18)F-FDG PET/CT imaging is feasible for monitoring response in patients with advanced penile carcinoma treated with induction chemotherapy. Our preliminary results suggest that PET/CT is potentially more reliable than CT alone.

Repeat dynamic sentinel node biopsy in locally recurrent penile carcinoma.

OBJECTIVE: To explore the role of repeat dynamic sentinel-node biopsy (SNB) in clinically node-negative patients with locally recurrent penile carcinoma after previous penile surgery and SNB. PATIENTS AND METHODS: Between 1994 and 2008, 12 patients (4% of the 304 in our prospectively maintained dynamic sentinel node database) with clinically node-negative groins had a repeat SNB for locally recurrent penile carcinoma after previous penile surgery and SNB. Five of these patients had previously had a unilateral inguinal node dissection for groin metastases. The median disease-free interval was 18 months. The protocol and technique of primary dynamic SNB and the repeat procedure were similar, including preoperative lymphoscintigraphy and blue-dye injection. Completion inguinal node dissection was only done if there was an involved sentinel node. RESULTS: No sentinel nodes were seen on preoperative lymphoscintigraphy in the five groins that had previously been dissected. A sentinel node was visualized on lymphoscintigraphy in the remaining 19 undissected groins. In 15 of these groins (79%) the sentinel node was identified during surgery. Histopathological analysis showed involved sentinel nodes in four groins of three patients. Additional metastatic nodes were found in one completion inguinal lymph node dissection specimen. During a median follow-up of 32 months after the repeat SNB, one patient developed a groin recurrence 14 months after a tumour-negative sentinel node procedure. CONCLUSIONS: Repeat dynamic SNB is feasible in clinically node-negative patients with locally recurrent penile carcinoma despite previous SNB.

Prospective evaluation of hybrid 18F-fluorodeoxyglucose positron emission tomography/computed tomography in staging clinically node-negative patients with penile carcinoma.

OBJECTIVE: To prospectively evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect occult metastasis in patients with clinically node-negative (cN0) penile carcinoma, as there is little information on the use of (18)F-FDG-PET/CT in penile carcinoma. PATIENTS AND METHODS: In 24 patients, scheduled to undergo dynamic sentinel-node biopsy, hybrid PET/CT was used before surgery to assess the nodal status of the cN0-groins. Six of the 24 patients were unilaterally cN0. Thus, 42 cN0-groins were evaluated for occult metastasis using PET/CT. All scans were assessed by two experienced nuclear physicians. The histopathological tumour status of the removed sentinel node was used as the standard of care to evaluate the PET/CT-results. RESULTS: Histopathology was tumour-positive in five of the 42 (12%) evaluated cN0-groins, two of which contained only micrometastases (<2 mm). One of the five tumour-positive cN0-groins was correctly predicted on the PET/CT-images. All false-negative PET/CT scans contained metastasis of

Surgical and Oncological Outcomes in Patients After Vascularised Flap Reconstruction for Locoregionally Advanced Penile Cancer.

BACKGROUND: Treatment of locoregionally advanced penile squamous cell carcinoma (LAPSCC) is challenging. The exact role (in terms of oncological benefit) of extensive surgery is not well established. Moreover, surgery invariably leads to large defects requiring reconstructive surgery. Rectus abdominis myocutaneous (RAM) and abdominal advancement flaps have an independent and constant blood supply, are easily harvested, and provide substantial skin coverage and soft tissue. OBJECTIVE: To determine the surgical and oncological outcomes in patients with LAPSCC undergoing surgical resection with RAM flaps. DESIGN, SETTING, AND PARTICIPANTS: From 2002 to 2016, a multi-institutional database identified 15 LAPSCC patients undergoing flap reconstructions. INTERVENTION: Local surgical resection with RAM or abdominal advancement flap reconstruction. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative and pathologic data were collected. Postoperative complications were identified using the Clavien-Dindo classification for surgical complications. RESULTS AND LIMITATIONS: Fifteen patients (median age 61 yr) were treated, ten with curative intent. Thirteen patients received induction chemotherapy. Thirteen of the 15 patients (87%) experienced wound complications, including five Clavien-Dindo grade III complications. In 11/15 patients (73%), the disease recurred (median recurrence-free interval 106 d). The majority of recurrences (91%) were locoregional, and in four cases the patient also had lesions in distant organs. Ten of the 15 patients (67%) died of their disease. The overall median follow-up interval was 10.5 mo. The study was limited by its retrospective design, the absence of quality-of-life measurements, and the cohort size. CONCLUSIONS: The results of this study show that surgical resection with reconstruction is associated with a risk of perioperative complications, including high-grade Clavien-Dindo complications. With a cure rate of 27%, surgery must be carefully considered and there is a need for alternative treatments. Lack of robust quality-of-life-data is also a serious shortcoming in the decision process for this patient category. PATIENT SUMMARY: Surgery in locoregionally advanced penile cancer has a low cure rate. Reconstruction of defects is surgically feasible, albeit with a high risk of complications. Furthermore, decision-making lacks robust data on quality of life after surgery.

Early wound complications after inguinal lymphadenectomy in penile cancer: a historical cohort study and risk-factor analysis.

BACKGROUND: Complication rates after inguinal lymph node dissection (ILND) are high. Risk factors for early wound complications after ILND in patients with penile carcinoma have not yet been studied. OBJECTIVES: To assess the frequency of early wound complications in a contemporary series and to identify clinical risk factors for early wound complications after ILND for penile carcinoma. DESIGN, SETTING, AND PARTICIPANTS: We evaluated 237 ILNDs in 163 patients with penile cancer treated between 2003 and 2012 at the Netherlands Cancer Institute. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the occurrence of wound infection, skin-flap problems, and seroma formation and graded complications using the modified Clavien system. Univariable and multivariable penalised mixed effects logistic regression was used to identify clinical risk factors for occurrence of any complication (grade ≥ 1) and of moderate to severe complications (grade ≥ 2). RESULTS AND LIMITATIONS: One complication or more occurred in 58% of the procedures, and 10% of those complications were severe. Wound infection occurred in 43%, seroma formation occurred in 24%, and skin-flap problems occurred in 16%. Palpable disease was the only factor associated with grade ≥ 1 complications in the univariable analysis (odds ratio [OR]: 0.43; p=0.02). In the multivariable model, after penalisation, no statistically significant risk factors remained. Univariable associations for grade ≥ 2 complications were present for body mass index (BMI; OR of 1.66 for a 5.8-point change in BMI; p=0.05) and sartorius muscle transposition (OR: 2.64; p=0.04). In the reduced multivariable model, the OR for sartorius muscle transposition was 2.12 (p=0.06) and for BMI was 1.76 (p=0.03). In addition, bilateral dissection approached significance in the multivariable model (OR: 2.17; p=0.06). This study is limited by its observational nature. CONCLUSIONS: Wound complication rates after ILND are high in this cohort. BMI, sartorius muscle transposition, and bilateral dissection were the factors most strongly associated with the occurrence of grade ≥ 2 wound complications.

Prognostic factors for occult inguinal lymph node involvement in penile carcinoma and assessment of the high-risk EAU subgroup: a two-institution analysis of 342 clinically node-negative patients.

BACKGROUND: The European Association of Urology (EAU) guidelines advise an elective bilateral lymphadenectomy in clinically node-negative (cN0) patients with high-risk penile carcinoma (≥pT2, G3, or lymphovascular invasion [LVI]). OBJECTIVE: Our aim was to assess prognostic factors for occult metastasis and to determine whether current EAU guidelines accurately stratify patients at high risk. DESIGN, SETTING, AND PARTICIPANTS: Data of 342 cN0 patients with histologically proven invasive penile squamous cell carcinoma who had undergone the current dynamic sentinel node biopsy (DSNB) protocol were analysed. A complete ipsilateral inguinal lymphadenectomy was only done if the sentinel node was tumour positive. MEASUREMENTS: The presence of occult metastasis was established by preoperative ultrasound and tumour-positive fine-needle aspiration cytology, tumour-positive sentinel nodes, and groin metastases during follow-up after a negative DSNB procedure. Median follow-up was 31 mo. RESULTS AND LIMITATIONS: Sixty-eight of 342 patients (20%) and 87 of 684 groins (13%) had occult nodal involvement including 6 patients (2%) with a groin metastasis after negative DSNB. Corpus spongiosum invasion, corpus cavernosum invasion, histologic grade, and LVI were each significant prognosticators for occult metastasis on univariate analysis. On multivariate analysis, grade (odds ratio [OR]: 3.3 for intermediate and 4.9 for poor, respectively) and LVI (OR: 2.2) remained predictive factors. In total, 245 patients (72%) were classified high risk according to EAU guidelines. Among them, the incidence of occult metastasis was 23% (57 of 245). A potential limitation of this study is the lack of external review. CONCLUSIONS: Histologic grade and LVI are independent prognostic factors for occult metastasis in penile carcinoma. Although both predictors are incorporated into the current EAU guidelines, the stratification of patients needing a lymph node dissection is inaccurate. Approximately 77% of high-risk patients (188 of 245) would have had a negative bilateral inguinal lymphadenectomy. For the time being, DSNB is considered a more suitable staging method than EAU risk stratification for an accurate determination of patients who require lymph node dissection.

Nodal staging in penile carcinoma by dynamic sentinel node biopsy after previous therapeutic primary tumour resection.

BACKGROUND: Dynamic sentinel node biopsy (DSNB) is used to evaluate the nodal status of patients with penile carcinoma and clinically node-negative groins. This minimally invasive procedure is usually done at the same time as the treatment of the primary tumour. OBJECTIVE: Our aim was to evaluate results of so-called postresection DSNB, that is, DSNB after previous resection of the penile tumour. DESIGN, SETTING, AND PARTICIPANTS: All 40 patients who had undergone DSNB after previous penile carcinoma resection with histopathologically tumour-negative margins between February 2003 and July 2009 were analysed. Twenty patients (50%) had known unilateral nodal involvement, and DSNB was used to stage the clinically normal contralateral groin. Hence the study concerned 60 groins without palpable nodes. The median time between primary tumour resection and DSNB was 2.8 mo. The technique of postresection DSNB was similar to the standard procedure. MEASUREMENTS: The sentinel node visualisation rate, identification rate, histopathologic results, and outcome during follow-up were investigated. RESULTS AND LIMITATIONS: A sentinel node was visualised on the lymphoscintigrams of 56 of the 60 eligible groins (93%). A sentinel node was identified intraoperatively in all these 56 groins. A median of two sentinel nodes were removed. Histopathologic analysis revealed involvement of seven groins (12%) in seven patients (18%). The median size of these metastases was 6mm. Additional dissemination was found in one completed ipsilateral inguinal node dissection specimen. No recurrences developed in the groins from which one or more tumour-free sentinel nodes had been taken during a median follow-up of 28 mo after the primary tumour resection. A potential limitation of this study is the short follow-up and relatively small cohort number. CONCLUSIONS: Postresection DSNB is a suitable procedure to stage clinically node-negative penile carcinoma after previous therapeutic primary tumour resection. The results seem similar to the favourable experience with DSNB in patients with their tumour still present.

Scanning with 18F-FDG-PET/CT for detection of pelvic nodal involvement in inguinal node-positive penile carcinoma.

BACKGROUND: Penile carcinoma patients with inguinal lymph node involvement (LNI) have an increased risk for pelvic nodal involvement with or without distant metastases. OBJECTIVE: To evaluate the diagnostic accuracy of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) with computed tomography (CT; 18F-FDG PET/CT) scanning in determining further metastatic spread in patients with tumour-positive inguinal nodes. DESIGN, SETTING, AND PARTICIPANTS: Eighteen patients with penile squamous cell carcinoma with unilateral or bilateral cytologically tumour-positive inguinal disease underwent whole-body 18F-FDG-PET/CT scanning for tumour staging. MEASUREMENTS: Images were blindly assessed by two nuclear medicine physicians. All scans were evaluated for pelvic nodal involvement per basin and for distant metastases. Histopathology (when available), radiologic imaging, and clinical follow-up (with a minimum of 1 yr) served as a reference standard. The diagnostic value of PET/CT scanning for predicting pelvic nodal involvement was evaluated using standard statistical methods. RESULTS AND LIMITATIONS: The reference was available in 28 of the 36 pelvic basins. Of the 11 tumour-positive pelvic basins, 10 were correctly predicted by PET/CT scan, as were all 17 tumour-negative pelvic basins. PET/CT scan showed a sensitivity of 91%, a specificity of 100%, a diagnostic accuracy of 96%, a positive predictive value of 100%, and a negative predictive value of 94% in detecting pelvic nodal involvement. Additionally, PET/CT scans showed distant metastases in five patients. In four patients, the presence of distant metastases could be confirmed, while in one patient, no radiologic confirmation was found for that particular lesion. A potential limitation is that the diagnostic accuracy of PET/CT scanning was calculated on 28 pelvic basins only. Furthermore, no comparison was made with conventional CT scans, as not all patients had undergone contrast-enhanced CT scans. CONCLUSIONS: PET/CT scanning appears promising for detecting pelvic lymph node metastases with great accuracy, and it identifies distant metastases in penile carcinoma patients with inguinal LNI. In our practice, PET/CT scanning has become part of routine staging in such patients.

Two-center evaluation of dynamic sentinel node biopsy for squamous cell carcinoma of the penis.

PURPOSE: Sentinel node biopsy is used to evaluate the nodal status of patients with clinically node-negative penile carcinoma. Its use is not widespread, and the majority of patients with clinically node-negative disease undergo an elective inguinal lymph node dissection. Reservations about the use of sentinel node biopsy include the fact that most current results come from one institution and the supposedly long learning curve associated with the procedure. The purpose of this study was to address these issues by analyzing results from two centers and by evaluating the learning curve. PATIENTS AND METHODS: All patients undergoing sentinel node biopsy for penile carcinoma at two centers were included. The sentinel node identification rate, false-negative rate, and morbidity of the procedure were calculated. RESULTS: from the first 30 procedures were assessed for a potential learning curve. Results A total of 323 patients with penile squamous cell carcinoma, which included 611 clinically node-negative groins, were scheduled for sentinel node biopsy. A sentinel node was found in 572 of the 592 groins (97%) that proceeded to sentinel node biopsy. In 79 groins, a sentinel node was positive for tumor. Six inguinal node recurrences occurred after a negative sentinel node procedure, all within 15 months after sentinel node biopsy. The combined false-negative rate was 7%. Complications occurred in 4.7% of explored groins. None of the false-negative procedures occurred in the initial 30 procedures. CONCLUSION: Sentinel node biopsy is a suitable procedure to stage clinically node-negative penile cancer, and it has a low complication rate. No learning curve was demonstrated in this study.