Concomitant vs Staged Therapeutic Inguinal Lymphadenectomy in Clinically Node Positive Penile Squamous Cell Carcinoma: Does It Make a Difference?

PURPOSE: Inguinal lymph node dissection within 3 months of primary tumor resection in penile cancer has been associated with longer recurrence-free and cancer-specific survival. However, the optimal timing and effect of lymphadenectomy performed concurrently at the time of primary lesion management on oncologic outcomes in clinically lymph node positive penile squamous cell carcinoma remains unknown. MATERIALS AND METHODS: An international, multicenter cohort of 966 penile cancer cases was queried for penile squamous cell carcinoma management after the year 2000, clinically lymph node positive status, and performance of penile surgery and inguinal lymph node dissection. Cohorts were stratified as concomitant if inguinal lymph node dissection and penile surgery occurred on the same date or staged when inguinal lymph node dissection was performed after penile resection. Rates and patterns of penile squamous cell carcinoma recurrence were reported. Distant recurrence-free, cancer-specific, and overall survival were estimated using Kaplan-Meier analyses and groups compared with log-rank testing. RESULTS: Of 253 contemporary men with clinically lymph node positive penile squamous cell carcinoma, 96 (38%) underwent concomitant inguinal lymph node dissection and 157 (62%) had inguinal lymph node dissection performed in a staged manner. Penile cancer was most likely to recur distantly (19%) followed by in the groin (14%) or pelvis (5%). There were no differences in distant recurrence-free, cancer-specific, or overall survival between management strategies. Multivariable analysis adjusting for stage, treatment center, and perioperative chemoradiation also demonstrated no recurrence-free, cancer-specific, or overall survival benefit between management strategies. CONCLUSIONS: Inguinal lymph node dissection performed concurrently with excision of the penile tumor for clinically node positive penile squamous cell carcinoma is not associated with differences in recurrence-free, cancer-specific, or overall survival compared to staged lymph node dissection.

Clinicopathological predictors of finding additional inguinal lymph node metastases in penile cancer patients after positive dynamic sentinel node biopsy: a European multicentre evaluation.

OBJECTIVE: To develop a predictive model for additional inguinal lymph node metastases (LNM) at inguinal lymph node dissection (ILND) after positive dynamic sentinel node biopsy (DSNB) using DSNB characteristics to identify a patient group in which ILND might be omitted. PATIENTS AND METHODS: We conducted a retrospective study of 407 inguinal basins with a positive DSNB in penile cancer patients who underwent subsequent ILND from seven European centres. From the histopathology reports, the number of positive and negative lymph nodes, presence of extranodal extension and size of the metastasis were recorded. Using bootstrapped logistic regression, variables were selected for the clinical prediction model based on the optimization of Akaike's information criterion. The area under the curve (AUC) of the receiver-operating characteristic curve was calculated for the resulting model. Decision curve analysis (DCA) was used to evaluate the clinical utility of the model. RESULTS: Of the positive DSNBs, 64 (16%) harboured additional LNM at ILND. Number of positive nodes at positive DSNB (odds ratio [OR] 2.19, 95% confidence interval (CI) 1.17-4.00; P = 0.01) and largest metastasis size in mm (OR 1.06, 95% CI 1.03-1.10; P = 0.001) were selected for the clinical prediction model. The AUC was 0.67 (95% CI 0.60-0.74). The DCA showed no clinical benefit of using the clinical prediction model. CONCLUSION: A small but clinically important group of basins harbour additional LNM at completion ILND after positive DSNB. While DSNB characteristics were associated with additional LNM, they did not improve the selection of basins in which ILND could be omitted. Thus, completion ILND remains necessary in all basins with a positive DSNB.

Update on penile sparing surgery for penile cancer.

PURPOSE OF REVIEW: Penile sparing surgery (PSS) is considered the standard of care in penile cancer where appropriate, as preservation of the penis may enable the patient to maintain urinary and sexual function. This review will focus on the latest developments over the past two years. RECENT FINDINGS: In this review, we discuss the latest findings in oncological outcomes in PSS, specifically glansectomy. We also introduce technology that may be useful in improving the precision of surgical resection margins in PSS. Finally, we consider the value of patient-reported outcome measures (PROMs) and consider how research in this area can be improved. SUMMARY: A recent study has found a correlation between local recurrences (LR) and worse overall and cancer-specific survival in glansectomy, which challenges the belief that LR do not confer worse oncological outcomes. Despite numerous studies evaluating PROMs in penile cancer/PSS, few of these studies provide quality evidence of the 'supportive care needs'. A shift in research is required to identify those men at most risk of distress and to identify ways to support men diagnosed with penile cancer.

Patterns of Recurrence following Inguinal Lymph Node Dissection for Penile Cancer: Optimizing Surveillance Strategies.

PURPOSE: Our primary objective is to detail the incidence, site, and timing of penile squamous cell carcinoma (pSCC) recurrence after inguinal lymph node dissection (ILND). MATERIALS AND METHODS: We performed a retrospective analysis of 551 patients who underwent ILND for pSCC from 2000 to 2017. The primary outcome was pSCC recurrence after ILND. Recurrences were identified and stratified by site. Timing of recurrence was determined. Multivariable logistic regression analysis determined associations with recurrence. Multivariable Cox regression analysis determined associations with overall survival (OS). Sub-group analysis of the distant recurrences analyzed timing and OS by site of distant recurrence. RESULTS: After ILND pSCC recurred in 176 (31.9%) patients. Median time to recurrence was 10 months for distant recurrences, 12 for inguinal, 10.5 for pelvic, and 44.5 for local. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 48 months of ILND, versus 127 months for local recurrences. Post-ILND recurrence was associated with pN2 (OR 1.99, 95% CI 1.0-4.1), and pN3 (OR 7.2, 95% CI 4.0-13.7). Patients who had local recurrence had similar OS to those without (HR 1.5, 95% CI 0.6-3.8), and worse OS was identified in patients with inguinal (HR 4.5, 95% CI 2.8-7.1), pelvic (HR 2.6, 95% CI 1.5-4.5), or distant (HR 4.0, 95% CI 2.7-5.8) recurrences. Patients with lung recurrences had worse OS than other sites (HR 2.2, 95% CI 1.1-4.3). CONCLUSIONS: Of the patients 31.9% had post-ILND recurrence associated with high pN staging. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 48 months, suggesting surveillance beyond this is low yield. Local recurrences occurred over a longer timeline, emphasizing necessity of long-term surveillance of the primary site.

Long-term multicentre experience of adjuvant radiotherapy for pN3 squamous cell carcinoma of the penis.

OBJECTIVE: To present the long-term adjuvant radiotherapy outcomes of patients with pN3 squamous cell carcinoma of the penis (SCCp) treated at two UK centres. PATIENTS AND METHODS: We conducted a retrospective audit of all pN3 SCCp patients, deemed suitable for adjuvant therapy by a specialist multidisciplinary team at St George's and Leeds Hospitals, who received adjuvant radiotherapy. Primary outcomes were recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Secondary outcomes were time to adjuvant treatment, frequency of in-field recurrence, site and side of recurrence, and dose and schedule of radiotherapy. RESULTS: A total of 146 patients were included: 121 completed radiotherapy, 4 did not complete radiotherapy and 21 did not start it. The median (interquartile range [IQR]) age was 59 (54-70)years. The 5-year RFS was 51%, CSS was 51% and OS was 44%. Adjuvant radiotherapy was started at a median (IQR) of 75 (48-106) days. A dose of 45 Gy in 20 fractions was most commonly used. Of the 125 patients who started adjuvant treatment, 55 relapsed. Of these relapses, 30 occurred in an inguinal or pelvic nodal station and 26 of the 30 were in a radiation field. Relapses in 18 of the 55 cases were in visceral sites only and seven were in both nodal (non-irradiated sites) and visceral sites. Doses of <50 Gy were used more commonly before 2013 and higher doses (>50 Gy) were more commonly used after 2013. CONCLUSIONS: Application of a standard radiotherapy protocol within a centralized supra-network setting has achieved survival outcomes that would appear better than those previously documented for either radiotherapy or chemotherapy in a cohort with solely pN3 disease. The addition of adjuvant chemotherapy may improve these outcomes further. These data suggest that adjuvant radiotherapy has a role to play in the management of men with pN3 SCCp.

Predictors of local recurrence and its impact on survival after glansectomy for penile cancer: time to challenge the dogma?

OBJECTIVES: To identify predictive pathological factors for local recurrence (LR) and to study the impact of LR on survival in patients treated with glansectomy for penile squamous cell carcinoma (pSCC). PATIENTS AND METHODS: We retrospectively studied patients treated with glansectomy at international, high-volume reference centres. We analysed histopathological predictors of LR, stratified patients into risk groups based on the number of risk factors present, and studied the impact of LR on survival outcomes using Kaplan-Meier survival analysis and stepwise Cox proportional hazards regression models. Subsequently, we performed sensitivity analyses excluding margin-positive cases, pT3 disease, and cN+ disease, or all of these factors. RESULTS: Across nine institutions, 897 patients were included, of whom 94 experienced LR. On multivariable analysis, presence of high-grade disease and pT3 stage were independent predictors of LR. LR-free survival rates significantly differed according to the number of risk factors present, with a hazard ratio (HR) of 1.90 (95% confidence interval [CI] 1.17-3.07; P = 0.01) for the intermediate-risk group (one risk factor) and 6.11 (95% CI 3.47-10.77; P < 0.001) for the high-risk group (two risk factors), using the low-risk group (no risk factors) as reference. Patients who experienced LR had significantly worse overall survival (OS; HR 2.89, 95% CI 2.02-4.14; P < 0.001) and cancer-specific survival (CSS; HR 5.64, 95% CI 3.45-9.22; P < 0.001). LR (HR 3.82, 95% CI 2.14-6.8; P < 0.001), lymphovascular invasion and cN status were significant predictors of decreased CSS. LR remained a strong predictor of both OS and CSS in all sensitivity analyses. CONCLUSIONS: Pathological T3 stage and presence of high-grade disease were independent histopathological predictors of LR after glansectomy for primary pSCC, which allowed risk stratification into three groups with significantly different risk of developing LR. Additionally, LR is related to poor OS and CSS, indicating that LR is a manifestation of underlying aggressive disease and clearly challenging the dogma of using organ-sparing surgery whenever possible since survival is unaffected by higher LR rates.

Endoscopic urethrotomy versus open urethroplasty for men with bulbar urethral stricture: the OPEN randomised trial cost-effectiveness analysis.

BACKGROUND: Bulbar urethral stricture is a common cause for urinary symptoms in men and its two main treatment options both have drawbacks with little evidence on their relative cost-effectiveness. Current guidelines on the management of recurrent bulbar urethral stricture have been predominantly based on expert opinion and panel consensus. OBJECTIVE: To assess the relative cost-effectiveness of open urethroplasty and endoscopic urethrotomy as treatment for recurrent urethral stricture in men. METHODS: Set in the UK National Health Service with recruitment from 38 hospital sites, a randomised controlled trial of open urethroplasty and endoscopic urethrotomy with 6-monthly follow-up over 24 months was conducted. Two hundred and twenty-two men requiring operative treatment for recurrence of bulbar urethral stricture and having had at least one previous intervention for stricture were recruited. Effectiveness was measured by quality- adjusted life years (QALYs) derived from EQ-5D 5L. Cost-effectiveness was measured by the incremental cost per QALY gained over 24 months using a within trial analysis and a Markov model with a 10-year time horizon. RESULTS: In the within trial, urethroplasty cost on average more than urethrotomy (cost difference: £2148 [95% CI 689, 3606]) and resulted in a similar number of QALYs on average (QALY difference: - 0.01 [95% CI - 0.17, 0.14)] over 24 months. The Markov model produced similar results. Sensitivity analyses using multiple imputation, suggested that the results were robust, despite observed missing data. CONCLUSIONS: Based on current practice and evidence, urethrotomy is a cost-effective treatment compared with urethroplasty. KEYPOINTS: Urethrotomy and urethroplasty both led to symptom improvement for men with bulbar urethral stricture-a common cause for urinary symptoms in men; Urethroplasty appeared unlikely to offer good value for money compared to urethrotomy based on current evidence. TRIAL REGISTRATION: ISRCTN: 98009168 (date: 29 November 2012) and it is also in the UK NIHR Portfolio (reference 13507). Trial protocol: The latest version (1.8) of the full protocol is available at: www.journalslibrary.nihr.ac.uk/programmes/hta/105723/ #/ and a published version is also available: Stephenson R, Carnell S, Johnson N, Brown R, Wilkinson J, Mundy A, et al. Open urethroplasty versus endoscopic urethrotomy-clarifying the management of men with recurrent urethral stricture (the OPEN trial): study protocol for a randomised controlled trial. Trials 2015;16:600. https://doi.org/10.1186/s13063-015-1120-4. Trial main clinical results publication: Goulao B, Carnell S, Shen J, MacLennan G, Norrie J, Cook J, et al. Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial), European Urology, Volume 78, Issue 4, 2020, Pages 572-580.

Identifying an optimal lymph node yield for penile squamous cell carcinoma: prognostic impact of surgical dissection.

OBJECTIVE: To evaluate the prognostic impact of lymph node yield (LNY) on survival outcomes for penile squamous cell carcinoma (SCC). PATIENTS AND METHODS: In all, 532 patients who underwent inguinal LN dissection (ILND) across tertiary referral centres from Europe, China, Brazil and North America were retrospectively evaluated. From this cohort, 198 patients received pelvic LND (PLND).We identified threshold values for ILND and PLND using receiver operating characteristic curves. We tested prognostic value of LNY for recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) using the Kaplan-Meir method and Cox proportional hazard regression models. RESULTS: The median (interquartile [IQR]) age was 59 (49-68) years and the median (IQR) follow-up after ILND was 28 (12-68.2) months. Overall, 85% of the patients had bilateral dissections. The median (IQR) number of inguinal LNs removed was 15 (10-22). Of those receiving PLND, The median (IQR) number of LNs was 13 (8-19). A LNY of ≥15 was used for dichotomisation of ILND patients, and a LNY of ≥9 was used in the PLND cohort. Patients with a LNY ≥15 had significantly better 5-year OS vs patients with a LNY <15 (70.1% vs 58.7%). On multivariable analyses, a LNY ≥15 was a predictor of OS (hazard ratio [HR] 0.68, P = 0.029). For cN0 patients, a LNY ≥15 was an independent predictor of RFS (HR 0.52, P = 0.043) and OS (HR 0.53, P = 0.021). In the PLND cohort, a LNY ≥9 was a predictor of RFS (HR 0.53, P = 0.032). CONCLUSIONS: Using one of the largest LND datasets to date, we found LNY to be a significant predictor of outcomes after lymphatic staging for penile SCC. Prospective validation is warranted.

Optimising the selection of candidates for neoadjuvant chemotherapy amongst patients with node-positive penile squamous cell carcinoma.

OBJECTIVES: To identify predictors of poor overall survival (OS) amongst patients with penile squamous cell carcinoma (pSCC) with clinical inguinal lymphadenopathy (cN+), in order to define the best candidates for neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Using an international, multicentre database of 924 patients with pSCC, we identified 334 men who harboured cN+ with available clinical and follow-up data. Lymph node involvement was defined either by the presence of palpable inguinal node disease or by preoperative computed tomography (CT) assessment. Fluorine-18 fluorodeoxyglucose positron-emission tomography (18 F-FDG-PET)/CT scan was performed based on clinical judgment of the treating physician. Regression-tree analysis generated a risk stratification tool for prediction of 24-month overall mortality (OM). Kaplan-Meier explored the OS benefit related to the use of NAC according to the regression-tree-stratified subgroups. RESULTS: Overall, 120 (35.9%), 152 (45.5%), and 62 (18.6%) patients harboured cN1, cN2, and cN3 disease. 18 F-FDG-PET/CT was performed in 48 (14.4%) patients, and 16 (4.8%) had inguinal and pelvic nodal PET detection. The median OS was 107 months, with a 24-month OS of 66%. At regression-tree analysis (area under the curve = 70%), patients with cN3 and cN2 with PET/CT-detected inguinal and pelvic nodal activity had a higher risk of 24-month OM (>50%). NAC was associated with improved 24-month OS rates (54% vs 33%) only in this subgroup of patients (P = 0.002), which was also confirmed after multivariable adjustment (hazard ratio 0.28, 95% confidence interval 0.13-0.62; P = 0.002). CONCLUSION: Patients with pSCC with cN3 or cN2 and inguinal and pelvic 18F-FDG-PET/CT scan detected disease had higher 24-month OM rates according to our regression-tree model. NAC was associated with improved OS only in these subgroups of patients. Our novel decision model may help to stratify cN+ patients, and identify those who most likely will benefit from NAC prior to radical surgical resection.

A risk calculator predicting recurrence in lymph node metastatic penile cancer.

OBJECTIVES: To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. PATIENTS AND METHODS: The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk-calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m-R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. RESULTS: Positive surgical margins, pN3 , and ILNM ratio were associated with higher recurrence rate. The 2-year OS rates were lower for patients with high (>37%) and intermediate (19-37%) compared to low (<19%) 24m-R risk of recurrence, for both the development (43% and 58% vs 83%, P < 0.001) and validation cohort (44% and 50% vs 85%, P < 0.001). Results were confirmed in the subgroup of patients who did not receive adjuvant treatment (P < 0.001), but not in patients who did receive adjuvant treatments in both the development and validation cohorts (P > 0.1). CONCLUSION: Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.

A study into the association between local recurrence rates and surgical resection margins in organ-sparing surgery for penile squamous cell cancer.

OBJECTIVE: To evaluate the significance of close surgical margins in organ-sparing surgery (OSS) in the treatment of penile squamous cell carcinoma (pSCC) and clinicopathological factors that may influence local recurrence. PATIENTS AND METHODS: At our tertiary referral centre, between March 2001 and September 2012, 332 patients treated with OSS for pSCC had clear surgical margins. As the focus was the impact of close clear margins on local recurrence, patients with positive margins were excluded for the purpose of this study. Our overall positive margin rate for OSS in penile cancer is 7.6% (42 patients). Analysis was carried out on an on-going prospective database, including prospective accurate pathological recording of surgical margins. Patients underwent OSS after multidisciplinary team (MDT) discussion. Local recurrence was the primary outcome measured and Fisher's exact test and time-to-recurrence curves were used in the analysis. All local recurrences were scrutinised by the MDT and were categorised into: true recurrences or metachronous new occurrences (i.e. tumours arising from a background of penile intraepithelial neoplasia and forming on an epithelial surface not related to the site of initial resection). A multivariate analysis was also conducted to elucidate other factors influencing local recurrence. RESULTS: In all, 64% of the patients had a <5 mm clear deep surgical margin, with 16% clear by <1 mm. Overall, 4% of patients had a true local recurrence, with a median time to recurrence of 6 months. In all, 53% were due to embolic spread, with residual occult local disease accounting for 47%. There was a statistically significant relationship between cavernosal involvement (P = 0.014) and lymphovascular invasion (LVI; P = 0.001) and local recurrence. Although multivariate analysis revealed that the extent of clear margin was not a predictor of disease (P = 0.405), we found an increased risk of local recurrence in the clear margin cohort of <1 mm compared to those of >1 mm (P < 0.001). Those patients considered to have metachronous tumours were scrutinised by our MDT, and eight patients (2.4%) were found to have new occurrences. Our overall proportion of patients therefore needing further treatment for either new occurrences or recurrent disease after OSS stands at 6.4%. CONCLUSIONS: Overall the presence of local recurrent disease in OSS in our experience is low (4%). We report an embolic mechanism of local recurrence, strongly suggested by the presence of cavernosal involvement and LVI. We conclude that a deep clear margin of >1 mm has a very low risk of local recurrence in penile OSS.

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.

Penile Doppler ultrasound in men with stuttering priapism and sickle cell disease -- a labile baseline diastolic velocity is a characteristic finding.

INTRODUCTION: Stuttering priapism (SP) is seen in sickle cell disease (SCD) and characterized by short-lived painful erections. Imbalanced vascular tone is the postulated cause and this may be reflected in changes in baseline penile blood flow as measured using penile Doppler ultrasound (PDU). AIM: The aim of this study was to investigate the baseline penile blood flow characteristics in men with SCD and SP, by comparing with men without SP. METHODS: PDU findings were retrospectively analyzed in 100 men during flaccid state. Nine men had SP (age range 20-40 years), 4 had Peyronie's disease (PD) (35-48 years), 67 men had erectile dysfunction (16-67 years), and 20 men had normal erectile function (18-42 years). MAIN OUTCOME MEASURES: The variables measured were peak systolic and end-diastolic velocities, and the Doppler velocity waveform. Values in men with SP were compared with those in the other groups. RESULTS: Median systolic and diastolic velocity was significantly higher in men with SP (systolic/diastolic velocity was 26/4 cm/second in men with SP vs. 13/0 cm/second, 14/0 cm/second, and 16/0 cm/second in men with PD, ED, and normal erectile function, respectively; P=0.0001). Men with SP had a characteristic low peripheral resistance (PR) waveform with fluctuating velocities; the diastolic velocity was consistently positive (2-7 cm/second) and fluctuated between +2 and +8 cm/second. In comparison, the other 91 men had high PR waveform and consistently negative diastolic velocity (range 0 to -2 cm/second). CONCLUSIONS: Men with SP had a unique baseline Doppler ultrasound waveform, with a low PR waveform and an elevated, variable cavernosal artery velocity. We propose that this may be the sonographic manifestation of a reduced, fluctuating smooth muscle tone and that PDU may have a role for diagnosis and therapeutic monitoring of SP.

Penile cancer: organ-sparing techniques.

To compare the oncological safety of treating patients with penile cancer with conservative techniques developed to preserve function, cosmesis and psychological well-being with more radical ablative strategies. We conducted an extensive review of the literature of penile-preserving and ablative techniques and report on the oncological as well as functional outcomes. There were no randomised studies comparing penile-preserving and ablative techniques. Most studies consisted of retrospective cohorts. The quality of evidence was level 3 at best. Cancer-specific survival is similar in penile-preserving and ablative approaches for low-stage disease. Penile preservation is better for functional and cosmetic outcomes and should be offered as a primary treatment method in men with low-stage penile cancer.

International case series of metastasis to penis.

Objectives: To evaluate clinical characteristics associated with survival in patients with metastases to the penis. Methods: After approval by the IRB, records of collaborating centres in Leuven, London, Rostock, Amsterdam and Tampa were screened for men presenting with metastatic disease to penis. Multivariate logistic regression analyses were used to identify covariables associated with survival. We analysed clinical data on 34 patients. Results: Primary sites were most frequently prostate (n = 14, 41%) and bladder (n = 9, 26%). Twenty-eight of 34 (82%) presented with metachronous penile metastases, and 11 (32%) patients had penile metastases as the sole metastatic site. Penile metastatic locations were most frequently in the corpora (n = 18; 53%). Seven (21%) patients with penile metastases had priapism on presentation. Systemic therapy was frequent and variable (chemotherapy n = 12; immunotherapy n = 5; hormones n = 3). Local management included either surgery (n = 10) or RT (n = 8). Twelve- and 24-month overall survival rate were 67% and 35%, respectively. No clinical parameter including primary histology, synchronous or metachronous metastases or priapism showed statistical survival benefit or detriment. Conclusion: Metastasis to penis arises most frequently from pelvic primaries. Priapism does not appear to correlate with survival in this large, well-defined series.

The Goal of Achieving High-Quality Surgical First-Line Therapy in Patients with Penile Cancer Is Important; However, Some Collective Efforts Are Still Required in Order to Reach It. Comment on Brassetti et al. Combined Reporting of Surgical Quality and Cancer Control after Surgical Treatment for Penile Tumors with Inguinal Lymph Node Dissection: The Tetrafecta Achievement. Curr. Oncol. 2023, 30, 1882-1892.

We read with great interest the manuscript by Brassetti et al. recently published in your journal and hope it will encourage discussion and debate around the optimization of the surgical management of patients with penile cancer (PECa) [...].

[Initial presentation of the Pentafecta score as a quality instrument for outcome evaluation of primary surgical treatment in patients with penile cancer]. / Erstvorstellung des Pentafecta-Scores als Qualitätsinstrument der Outcome-Bewertung einer chirurgischen Primärtherapie an Patienten mit Peniskarzinom.

BACKGROUND: Recently, the Tetrafecta score has been published as the first instrument for assessing the quality of primary surgical treatment for penile cancer (PECa). An external scientific discussion about the defining criteria is still pending and forms the study objective. MATERIAL AND METHODS: An international working group consisting of 12 urologists and an oncologist with clinical and academic-scientific expertise in penile cancer was established. In a modified four-stage Delphi process, a total of 13 criteria for PECa patients in clinical AJCC stages 1-4 (T1-3N0-3, but M0) were defined, incorporating the Tetrafecta criteria. Each expert had to select five of these criteria in a secret ballot to generate an individual Pentafecta score. Subsequently, the experts' ratings were aggregated and a final Pentafecta score was formed. RESULTS: None of the original Tetrafecta criteria were included in the final Pentafecta score, which consisted of the following criteria: 1) organ preservation, if possible (≤T2), but always with negative surgical margins, 2) bilateral inguinal lymph node dissection (ILND) from ≥pT1G2N0, 3) perioperative chemotherapy if indicated by guidelines, 4) ILND, if indicated, within a maximum of three months after primary tumour resection, and 5) the treating clinic should perform at least 15 primary surgical treatments in PECa patients. Only in seven out of the 13 experts (54%), a strong correlation was found between individual Pentafecta scores and the final Pentafecta score (rsp >0.60). CONCLUSION: Based on a moderated voting process among international PECa experts, a Pentafecta score was developed as a quality assurance instrument for primary surgical treatment, which now needs to be validated using patient-relevant and patient-reported endpoints.

Corporal Skip Metastases in Penile Squamous Cell Carcinoma: An Unknown and Distinct Pattern of Spread with Poor Prognosis.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is characterised by stepwise lymphatic dissemination. Skip metastases (SkMs) are rare metastases in the corpus cavernosum or spongiosum without continuity to the primary tumour or its resection site. OBJECTIVE: To assess the distinct pattern of spread in SkM+ patients and the effect of SkM on prognosis. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective analysis of patients with SkM+ PSCC at ten high-volume international referral centres between January 2006 and May 2022. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated histopathological data, primary lymph node (LN) staging, and metastatic spread. We included a cohort of patients matched for pT stage, LN status, and grade who did not have SkM (SkM-) to compare the SkM prognosis and predictive value for cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Among the 63 SkM+ patients who met our inclusion criteria, the SkM diagnosis was synchronous in 54.0% and metastases were mostly located in the corpus cavernosum. SkM was symptomatic in 14% of cases, was detected on imaging in 32%, and was found incidentally on pathological examination in 27%. Fifty-one patients (81%) presented with positive LNs and 28 (44%) developed distant metastases. Seven patients (11%) presented with or developed distant metastasis without displaying any LN involvement. The 2-yr cancer-specific survival estimates were 36% (95% confidence interval [CI] 25-52%) for SkM+ and 66% (95% CI 55-80%) for matched SkM- patients (p < 0.001). On multivariable Cox regression analysis, SkM presence was an independent predictor for higher CSM (hazard ratio 2.05, 95% CI 1.06-4,12; p = 0.03). CONCLUSIONS: PSCC-related SkM is associated with aggressive disease behaviour and poor survival outcomes. Palpation of the entire penile shaft is essential, and distant staging is recommended in patients suspected of having SkM owing to the tendency for distant metastatic spread. PATIENT SUMMARY: We investigated outcomes for patients with cancer of the penis who had metastases in the tissues responsible for erection. We found that metastases in this location were associated with poor prognosis, even in the absence of more typical spread of cancer via the lymph nodes.