Penile cancer care in the Netherlands: increased incidence, centralisation, and improved survival.

OBJECTIVE: To evaluate penile squamous cell carcinoma (PSCC) incidence and centralisation trends in the Netherlands over the past three decades, as well as the effect of centralisation of PSCC care on survival. PATIENTS AND METHODS: In the Netherlands PSCC care is largely centralised in one national centre of expertise (Netherlands Cancer Institute [NCI], Amsterdam). For this study, the Netherlands Cancer Registry, an independent nationwide cancer registry, provided per-patient data on age, clinical and pathological tumour staging, follow-up, and vital status. Patients with treatment at the NCI were identified and compared to patients who were treated at all other centres. The age-standardised incidence rate was calculated with the European Standard Population. The probability of death due to PSCC was estimated using the relative survival. Multivariable Cox regression analysis was performed to evaluate predictors of survival. RESULTS: A total of 3160 patients were diagnosed with PSCC between 1990 and 2020, showing a rising incidence (P < 0.001). Annual caseload increased at the NCI (1% in 1990, 65% in 2020) and decreased at other (regional) centres (99% to 35%). Despite a relatively high percentage of patients with T2-4 (64%) and N+ (33%) at the NCI, the 5-year relative survival was higher (86%, 95% confidence interval [CI] 82-91%) compared to regional centres (76%, 95% CI 73-80%, P < 0.001). Patients with a pathological T2 tumour were treated with glans-sparing treatment more often at the reference centre than at the regional centres (16% vs 5.0%, P < 0.001). After adjusting for age, histological grading, T-stage, presence of lymph node involvement and year of diagnosis, treatment at regional centres remained a predictor for worse survival (hazard ratio 1.22, 95% CI 1.05-1.39; P = 0.006). CONCLUSION: The incidence of PSCC in the Netherlands has been gradually increasing over the past three decades, with a noticeable trend towards centralisation of PSCC care and improved relative survival rate.

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.

Patterns of Recurrence and Survival After Pelvic Treatment for Locally Advanced Penile Cancer.

Background: Penile cancer (PeCa) is rare, and the survival of patients with advanced disease remains poor. A better understanding of where treatment fails could aid the development of new treatment strategies. Objective: To describe the disease course after pelvic lymph node (LN) treatment for PeCa. Design setting and participants: We retrospectively analysed 228 patients who underwent pelvic LN treatment with curative intent from 1969 to 2016. The main treatment modalities were neoadjuvant chemotherapy, chemoradiation, and pelvic LN dissection. Outcome measurements and statistical analysis: In the case of multiple recurrence locations, the most distant location was taken and recorded as follows: local (penis), regional (inguinal and pelvic LN), and distant (any other location). A competing risk analysis was used to calculate the time to recurrence per location, and a Kaplan-Meier analysis was used for overall survival (OS). Results and limitations: The median follow-up of the surviving patients was 79 mo. The reason for pelvic treatment was pelvic involvement on imaging (29%), two or more tumour-positive inguinal LNs (61%), or inguinal extranodal extension (52%). More than half of the patients (61%) developed a recurrence. The median recurrence-free survival was 11 mo. The distribution was local in 9%, regional in 27%, and distant in 64% of patients. The infield control rate of nonsystemically treated patients was 61% (113/184). From the start of pelvic treatment, the median OS was 17 mo (95% confidence interval 12-22). After regional or distant recurrence, all but one patient died of PeCa with median OS after a recurrence of 4.4 (regional) and 3.1 (distant) mo. This study is limited by its retrospective nature. Conclusions: The prognosis of PeCa patients treated on their pelvis who recur despite locoregional treatment is poor. The tendency for systemic spread emphasises the need for more effective systemic treatment strategies. Patient summary: In this report, we looked at the outcomes of penile cancer patients in an expert centre undergoing various treatments on their pelvis. We found that survival is poor after recurrence despite locoregional treatment. Therefore, better systemic treatments are necessary.

Outcomes for Atypical Tumor Recurrences Following Minimally Invasive Kidney Cancer Operations.

Background: We managed a cohort of patients treated with minimally invasive surgery (MIS) for a kidney tumor presenting with atypical tumor recurrence (ATR) involving port sites, intraperitoneal carcinomatosis, and nephrectomy bed/perinephric tumor implants. Objective: To determine the clinical characteristics, management, and oncologic outcomes for patients with localized renal cell carcinoma (RCC) who develop ATR following curative-intent MIS for partial or radical nephrectomy. Design setting and participants: The study cohort comprised patients from 1999 to 2021 with localized RCC managed at Memorial Sloan Kettering Cancer Center (New York, NY, USA) after MIS for partial or radical nephrectomy who developed ATR. Outcome measurements and statistical analysis: We collected data on clinicopathologic characteristics, treatments, time to ATR, and overall survival. Results and limitations: The median age of the 58 RCC patients was 61 yr. Forty-one patients (71%) were male, 26 (45%) had robot-assisted operations, and 39 (67%) had clear cell RCC. Twenty-nine patients had stage pT1 disease (50%) and ten (17%) had positive surgical margins. The most common ATR site was perinephric/nephrectomy bed implants (n = 28, 48%). Management included: surgical resection alone (n = 11, 19%), systemic therapy alone (n = 12, 21%), surgical resection and systemic therapy (n = 17, 29%), and palliative care (n = 8, 14%). At median follow-up of 59 mo (interquartile range [IQR] 28-92), the median time to ATR was 12 mo (IQR 5-28). Overall survival at 5 yr was 69.0% (95% confidence interval 57.4-83.1%) with only nine patients alive with no evidence of disease. Limitations include the potential for referral, detection, and selection biases, as well as uncertainty regarding the true incidence of ATR. Conclusions: ATR following MIS for partial or radical nephrectomy is an understudied, poor prognostic event which leads to a heavy treatment burden. Further investigation into its etiology and means of prevention is warranted. Patient summary: Patients experiencing recurrence of kidney cancer in an atypical site require a heavy treatment burden and have a guarded overall prognosis. Continued research is needed to determine the precise incidence of these recurrences and identify methods for mitigating them.

Primary Renal Tumour Response in Patients Treated with Nivolumab and Ipilimumab for Metastatic Renal Cell Carcinoma: Real-world Data Assessment.

Following CARMENA and SURTIME, patients with metastatic renal cell carcinoma (mRCC) and International Metastatic RCC Database Consortium (IMDC) intermediate and poor risk receive systemic therapy with the primary tumour (primary) in place, with the option of deferred cytoreductive nephrectomy (CN) in responding patients. We retrospectively analysed the safety and efficacy of first-line nivolumab/ipilimumab in 71 primary mRCC patients (42.3% IMDC poor risk; 43.6% with more than three metastatic sites). The baseline mean primary diameter was 9.3 cm and median follow-up was 11.5 mo. Of 69 patients with at least one follow-up computed tomography scan, 23 (33.3 %) had a partial response (PR) of the primary after a median of 4.8 mo, which was associated with a 91.3% overall response rate at metastatic sites (MSs) and absence of progressive disease, irrespective of the IMDC risk. The complete response (CR) rate at MSs (n = 7 [10.1%]) is similar to the CR rate in CheckMate 214. Thirteen deferred CNs were performed (18.8%) after a median of 13 mo, rendering four patients disease free. Only 4.3% of primaries progressed; grade 3-4 immune-related adverse events occurred in 31.9%. Irrespective of the IMDC risk, patients with a PR in the primary had a 1-yr overall survival rate of 89% versus 67% in those without (p = 0.012). PATIENT SUMMARY: Patients with metastatic kidney cancer receiving immunotherapy with nivolumab and ipilimumab had superior response at metastatic sites and better survival irrespective of International Metastatic RCC Database Consortium (IMDC) risk.

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).

Outcome after resection of occult and non-occult lymph node metastases at the time of nephrectomy.

PURPOSE: There is sparse evidence on outcomes of resected occult LN metastases at the time of nephrectomy (synchronous disease). We sought to analyse a large international cohort of patients and to identify clinico-pathological predictors of long-term survival. MATERIALS AND METHODS: We collected data of consecutive patients who underwent nephrectomy and LND for Tany cN0-1pN1 and cM0-1 RCC at 7 referral centres between 1988 and 2019. Patients were stratified into four clinico-pathological groups: (1) cN0cM0-pN1, (2) cN1cM0-pN1(limited, 1-3 positive nodes), (3) cN1cM0-pN1(extensive, > 3 positive nodes), and (4) cM1-pN1. Overall survival (OS) was estimated using the Kaplan-Meier method, and associations with all-cause mortality (ACM) were evaluated using Cox models with multiple imputations. RESULTS: Of the 4370 patients with LND, 292 patients with pN1 disease were analysed. Median follow-up was 62 months, during which 171 patients died. Median OS was 21 months (95% CI 17-30 months) and the 5-year OS rate was 24% (95% CI 18-31%). Patients with cN0cM0-pN1 disease had a median OS of 57 months and a 5-year OS rate of 43%. 5-year OS (median OS) decreased to 29% (33 months) in cN1cM0-pN1(limited) and to 23% (23 months) in cN1cM0-pN1(extensive) patients. Those with cM1-pN1 disease had the worst prognosis, with a 5-year OS rate of 13% (9 months). On multivariable analysis, age (p = 0.034), tumour size (p = 0.02), grade (p = 0.02) and clinico-pathological group (p < 0.05) were significant predictors of ACM. CONCLUSION: Depending on clinico-pathological group, grade and tumour size, 5-year survival of patients with LN metastases varies from 13 to 43%. Patients with resected occult lymph node involvement (cN0/pN1 cM0) have the best prognosis with a considerable chance of long-term survival.

Topographic distribution of first landing sites of lymphatic metastases from patients with renal cancer.

INTRODUCTION AND OBJECTIVE: Adjuvant studies with checkpoint inhibitors have attracted new interest in accurate pathological lymph node (LN) staging in renal cell carcinoma. Sentinel lymph node (SN) studies in cN0 patients revealed the pattern of lymphatic radiotracer drainage from renal tumors. The aim of this study was to describe the location of single- or oligometastatic LN and analyze if the topography of these first landing sites matches the drainage pattern observed in SN studies of renal tumors. MATERIALS AND METHODS: We collected data from 8 referral centers from 1990 to 2018 of all patients with pT1-4 cN0 or cN1 M0 renal cell carcinoma with pathologically confirmed single- or oligometastases in locoregional LN. The location of LN metastases, number, size of metastatic LN, and survival were analyzed using descriptive statistics with SPSS version 22 (IBM, Chicago, IL). RESULTS: From 3,794 patients with histologically confirmed pN1, a total of 76 patients (2%) with single- or oligometastatic pN1 were identified, of whom 24 (31.6%) and 52 (68.4%) were cN0 and cN1, respectively. On the left side, LN metastases were predominantly located in the para-aortal (48.0%; 95% confidence interval [CI] 29.22-63.12%) and hilar (31.42%; 95% CI 17.4-49.4%) area. On the right side, metastases located in retrocaval (26.82%; 95% CI 14.7-43.2%), hilar (26.82%; 95% CI 14.7-43.2%), interaortocaval (26.82%; 95% CI 14.7-43.2%), and paracaval (17.07%; 95% CI 7.6-32.6%) LNs. These landing sites exactly matched the lymphatic drainage pattern of intratumorally injected radiotracer reported in SN studies for both sides. CONCLUSIONS: Single- or oligometastatic LNs in renal cancer are mainly located in the hilar, retro-, para, and interaortocaval region on the right side and para-aortal region on the left side. These first landing sites match the drainage pattern reported in SN trials.

Ureterocolic fistula detected by mercaptoacetyltriglycine (MAG-3) diuretic renography including single photon emission CT and low-dose CT (SPECT-CT).

We describe the case of a 60-year-old man with a ureterocolic fistula following laparoscopic sigmoid resection. The fistulous tract between the left ureter and sigmoid colon was detected by mercaptoacetyltriglycine diuretic renography including single photon emission CT with low-dose CT. Ureteroneocystostomy was successfully performed.

Sentinel Lymph Node Biopsy in Renal Tumors: Surgical Technique and Safety.

OBJECTIVE: To understand uncertainties and knowledge gaps regarding lymphatic drainage in renal tumors, we performed 2 prospective studies to demonstrate regional lymph node (LN) drainage with sentinel lymph node (SN) imaging and biopsy. Here, we report the technique and perioperative safety of retroperitoneal SN dissection with different surgical approaches. METHODS: Seventy three patients from the 2 trials were included in the analysis. Patients had cT1-2N0M0 renal tumors (

A Phase II, single-arm trial of neoadjuvant axitinib plus avelumab in patients with localized renal cell carcinoma who are at high risk of relapse after nephrectomy (NEOAVAX).

Surgery is the standard treatment for nonmetastatic renal cell carcinoma. Despite curative intent, patients with a high risk of relapse have a 5-year metastasis-free survival rate of only 30% and prevention of recurrence is an unmet need. In a Phase III trial (JAVELIN Renal 101), progression-free survival of axitinib + avelumab was superior to sunitinib with a favorable objective response rate and no added toxicity profiles as known for axitinib or avelumab single agent. NEOAVAX is designed as open label, single arm, Phase II trial with a Simon's two-stage design evaluating neoadjuvant axitinib + avelumab followed by complete surgical resection in 40 patients with high-risk nonmetastatic clear-cell renal cell carcinoma. Primary end point is remission of the primary tumor (RECIST 1.1; Response Evaluation Criteria In Solid Tumors) following neoadjuvant therapy. Secondary end points include disease-free survival, overall survival, rate of metastasis and local recurrence, safety, and tolerability. Exploratory end points include investigation of effects on neoangiogenesis, immune infiltrates and myeloid-derived suppressor cell components to support a rationale for the combined use of axitinib and avelumab (NCT03341845).

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.

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.

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.

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.