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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.
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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.
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OBJECTIVE: Patients with advanced penile squamous cell cancer have a poor prognosis and can benefit from early palliative care consultation. We built a model to identify those patients most likely to benefit. METHODS: Patients with penile squamous cell cancer undergoing inguinal lymph node dissection were identified from the National Cancer Database (NCDB) and a multi-institutional international dataset (INT). A multivariable Cox proportional hazards model for overall survival (OS) was developed using the NCDB and applied to the INT dataset. Parameters were used to make receiver operating characteristic (ROC) curves. ROC-related criteria were optimized to identify a predictive probability cut point and dichotomize patients from INT into risk groups for limited OS of <6 and <12 months. RESULTS: NCDB had 860 deaths; 105 (5%) at 6 months and 296 (15%) at 12 months. INT had 257 deaths; 56 (8%) at 6 months and 124 (18%) at 12 months. Limited OS was associated with older age, greater T and N stage, and fewer lymph nodes removed. Optimized ROC criteria using the OS <6 months curve best dichotomized INT patients into high-risk group with median OS of 24 months (95% CI 18-34) and low-risk group with median OS of 174 months (95% CI 120-NE). CONCLUSION: We developed a simple model that could be used as a screening tool for early palliative care referral.
Subject(s)
Carcinoma, Squamous Cell , Penile Neoplasms , Male , Humans , Penile Neoplasms/pathology , Retrospective Studies , Lymph Node Excision , Lymph Nodes/surgery , Lymph Nodes/pathology , Carcinoma, Squamous Cell/pathology , Patient Care Planning , Neoplasm Staging , PrognosisABSTRACT
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.
Subject(s)
Penile Neoplasms , Male , Humans , Penile Neoplasms/diagnosis , Penile Neoplasms/surgery , Penile Neoplasms/pathology , Treatment Outcome , Lymph Node ExcisionABSTRACT
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) [...].
Subject(s)
Penile Neoplasms , Male , Humans , Penile Neoplasms/surgery , Penile Neoplasms/pathology , Goals , Lymphatic Metastasis , Lymph Node ExcisionABSTRACT
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.
Subject(s)
Carcinoma, Squamous Cell , Penile Neoplasms , Male , Humans , Groin , Penile Neoplasms/pathology , Inguinal Canal , Neoplasm Recurrence, Local/pathology , Lymph Node Excision , Carcinoma, Squamous Cell/pathology , Lymph Nodes/surgery , Lymph Nodes/pathology , Neoplasm StagingABSTRACT
OBJECTIVES: We present a summary of penile cancer, its epidemiology, risk factors, and possible clinical presentations. We discuss a range of penile lesions that indicate an underlying penile malignancy. We also consider some nonmalignant penile lesions that may be confused with penile cancer. DATA SOURCES: Sources of information include original research articles, review journal articles, and textbooks, which have been referenced in the article. CONCLUSION: Penile cancer is a rare disease, although geographical variations exist. Due to this rarity, many health care professionals may overlook a diagnosis of penile cancer. Malignant penile lesions may often be confused with benign lesions and vice versa. One needs to have a high index of suspicion to not overlook this important diagnosis. IMPLICATIONS FOR NURSING PRACTICE: Referral to specialists should be made if malignancy is suspected, if the diagnosis is uncertain, or if the lesion persists despite reasonable treatment with steroids and other creams.
Subject(s)
Penile Neoplasms , Humans , Male , Penile Neoplasms/diagnosis , Penile Neoplasms/pathology , Penile Neoplasms/therapy , Risk FactorsABSTRACT
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.
Subject(s)
Penile Neoplasms , Humans , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Male , Models, Statistical , Neoplasm Staging , Penile Neoplasms/pathology , Penile Neoplasms/surgery , Prognosis , Retrospective Studies , Sentinel Lymph Node Biopsy/methodsABSTRACT
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.
Subject(s)
Penile Neoplasms , Humans , Male , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/surgery , Organ Sparing Treatments/adverse effects , Penile Neoplasms/surgery , Penis/surgery , Urologic Surgical Procedures, Male/adverse effectsABSTRACT
With the passage of time, there has been a major paradigm shift in the surgical management of penile cancer from radical to organ preserving penile surgical techniques, with closer surgical margins which offer good oncological, cosmetic and functional outcomes with improved physical and psychosexual well-being. This article aims to provide an update of the current organ preserving surgical strategies for penile cancer.
Subject(s)
Penile Neoplasms , Humans , Male , Margins of Excision , Organ Sparing Treatments/methods , Penile Neoplasms/surgery , Penis/surgery , Urologic Surgical Procedures, Male/methodsABSTRACT
OBJECTIVES: To identify incidence and risk factors for upstaging from cN1 to pN2/N3 at inguinal lymphadenectomy (ILND) for penile cancer (pSCC). Our secondary objective is to assess survival outcomes and associations for cN1 patients undergoing ILND. SUBJECTS/PATIENTS AND METHODS: Patients with pT≥1cN1cM0 pSCC who underwent bilateral ILND and had complete data were identified in a multi-institutional international cohort from 8 referral centers in 7 countries diagnosed from 1980 to 2017. Upstaging was defined as pN2/N3 at ILND. Multivariable logistic regression analysis was used to determine associations with upstaging, and Cox multivariable logistic regression analysis to determine associations with overall survival (OS). RESULTS: Of 144 patients were included in the final study population. 84 patients (58%) were upstaged from cN1 to pN2/N3, and 25 (17%) were down staged to pN0. Upstaging was associated with pT3/T4 (OR 4.1, 95%CI 1.5-11.7, P < 0.01) and pTX (OR 7.1, 95CI 1.6-51.1, Pâ¯=â¯0.02). Age, smoking status, HPV status, and LVI were not associated with upstaging. Age (HR 1.03/y, 95%CI 1.01-1.06, P < 0.01) and upstaging (HR 2.8, 95%CI 1.3-5.9, P < 0.01) were associated with worse OS. Upstaged patients had a 5-year OS of 49%, compared with 86% for patients who were not upstaged. CONCLUSION: The majority of cN1 pSCC patients harbor a higher-risk disease state than their clinical staging suggests, especially those with higher pT stages. More intensive pre-operative workup may be warranted for these patients to identify upstaging prior to ILND and potentially qualify them for neoadjuvant chemotherapy or clinical trials.
Subject(s)
Carcinoma, Squamous Cell/pathology , Inguinal Canal/pathology , Lymph Nodes/pathology , Penile Neoplasms/pathology , Aged , Carcinoma, Squamous Cell/mortality , Humans , Male , Middle Aged , Penile Neoplasms/mortality , Risk Factors , Survival Analysis , Treatment OutcomeABSTRACT
Dynamic sentinel lymph node biopsy (DSNB) and radical inguinal lymph node dissection (ILND) are important in the management of penile cancer patients, but high-level evidence for preoperative, perioperative, and postoperative management remains scarce. According to an online survey of 35 surgeons from ten European countries, 57% perform >10 ILND procedures per year and 86% offer DSNB. Furthermore, management differs substantially for dye injection site, use of lymphoscintigraphy, preferred incision sites, techniques for lymphatic control, duration of empiric antibiotic therapy, perioperative thromboprophylaxis, time points for drain removal, and definition of the ILND dissection floor. Consensus was observed for the use of perioperative antibiotics (although not duration and type) and the borders for ILND template definitions. We conclude that there is significant variation in patient management among eUROGEN penile cancer surgeons. This heterogeneity may confound multicentre studies; therefore, a consensus to standardise inguinal node management in penile cancer across European penile cancer centres is warranted. PATIENT SUMMARY: Our survey reveals that preferences and surgical techniques for inguinal lymph node sampling and removal varies significantly between European penile cancer surgeons. Consensus is needed to standardise the management approach for penile cancer.
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CONTEXT: Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are associated with a high recurrence rate, especially in recurrent USD. Adjunctive measures, such as local drug injection, have been used in an attempt to reduce recurrence rates. OBJECTIVE: To systematically review evidence for the efficacy and safety of adjuncts used alongside minimally invasive treatment of USD. EVIDENCE ACQUISITION: A systematic review of the literature published between 1990 and 2020 was conducted in accordance with the PRISMA checklist. EVIDENCE SYNTHESIS: A total of 26 studies were included in the systematic review, from which 13 different adjuncts were identified, including intralesional injection (triamcinolone, n = 135; prednisolone, n = 58; mitomycin C, n = 142; steroid-mitomycin C-hyaluronidase, n = 103, triamcinolone-mitomycin C-N-acetyl cysteine, n = 50; platelet-rich plasma, n = 44), intraluminal instillation (mitomycin C, n = 20; hyaluronic acid and carboxymethylcellulose, n = 70; captopril, n = 37; 192-iridium brachytherapy, n = 10), application via a lubricated catheter (triamcinolone, n = 124), application via a coated balloon (paclitaxel, n = 106), and enteral application (tamoxifen, n = 30; deflazacort, n = 36). Overall, 13 randomised controlled trials were included in the meta-analysis. Use of any adjunct was associated with a lower rate of USD recurrence (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.50; p < 0.001) compared to no adjunct use. Of all the adjuncts, mitomycin C was associated with the lowest rate of USD recurrence (intralesional injection: OR 0.23, 95% CI 0.11-0.48; p < 0.001; intraluminal injection: OR 0.11, 95% CI 0.02-0.61; p = 0.01). Urinary tract infection (2.9-14%), bleeding (8.8%), and extravasation (5.8%) were associated with steroid injection; pruritis of the urethra (61%) occurred after instillation of captopril; mild gynaecomastia (6.7%) and gastrointestinal side effects (6.7%) were associated with oral tamoxifen. CONCLUSIONS: Adjuncts to minimally invasive treatment of USD appear to lower the recurrence rate and are associated with a low adjunct-specific complication rate. However, the studies included were at high risk of bias. Mitomycin C is the adjunct supported by the highest level of evidence. PATIENT SUMMARY: We reviewed studies on additional therapies (called adjuncts) to minimally invasive treatments for narrowing of the urethra in men. Adjuncts such as mitomycin C injection result in a lower recurrence rate compared to no adjunct use. The use of adjuncts appeared to be safe and complications are uncommon; however, the studies were small and of low quality.
Subject(s)
Urethral Stricture , Captopril , Humans , Injections, Intralesional , Male , Mitomycin , Recurrence , Tamoxifen , Triamcinolone , Urethra , Urethral Stricture/surgeryABSTRACT
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.
Subject(s)
Carcinoma, Squamous Cell/surgery , Lymph Node Excision , Lymphatic Metastasis/therapy , Neoplasm Recurrence, Local/epidemiology , Penile Neoplasms/surgery , Aged , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Disease-Free Survival , Follow-Up Studies , Humans , Inguinal Canal , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Penile Neoplasms/diagnosis , Penile Neoplasms/mortality , Penile Neoplasms/pathology , Retrospective StudiesABSTRACT
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.
Subject(s)
Cost-Benefit Analysis , Endoscopy/economics , Urethra/surgery , Urethral Stricture/surgery , Humans , Male , Recurrence , Urologic Surgical Procedures, Male/economics , Urologic Surgical Procedures, Male/methodsABSTRACT
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.
Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Penile Neoplasms/radiotherapy , Aged , Carcinoma, Squamous Cell/pathology , Humans , Male , Middle Aged , Neoplasm Staging , Penile Neoplasms/pathology , Radiotherapy, Adjuvant , Retrospective Studies , Time FactorsABSTRACT
BACKGROUND: Data on the impact of human papillomavirus (HPV) infection status and outcomes for perioperative treatments for patients with lymph node-involved penile squamous-cell carcinoma (PSCC) are lacking. OBJECTIVE: To analyze the benefit from perioperative radiotherapy (RT) for PSCC according to HPV infection status. DESIGN, SETTING, AND PARTICIPANTS: In an international multicenter database of 1254 patients with PSCC who received inguinal lymph node dissection (ILND), 507 had suitable clinical information. INTERVENTION: ILND, with or without chemotherapy or RT for involved lymph nodes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier and restricted mean survival time (RMST) analyses for overall survival (OS) were performed for all patients and after propensity score-matching (PSM; n = 136), for which patient age, histology, type of penile surgical procedure, pathological tumor and nodal stage, ILND laterality, pelvic LND, and perioperative treatment were taken into account when assessing differences between HPV+ and HPV- patients. Finally, we looked at genomic alterations in PSCC using data from the Foundation Medicine database (n = 199) to characterize HPV+ PSCC. RESULTS AND LIMITATIONS: Patients with HPV+ PSCC (n = 86; 17%) had lower clinical N stage (p < 0.001) and inguinal lymph node metastasis density (p < 0.001). Perioperative RT was delivered in 49 patients (9.7%), with the vast majority receiving adjuvant RT (n = 40). HPV+ patients had similar median OS (p = 0.1) but longer RMST than HPV- patients at different time points. Nevertheless, HPV+ patients treated with perioperative RT exhibited longer median OS (p = 0.015) and longer RMST compared to HPV- patients. In the PSM cohorts, HPV+ status remained significantly associated with longer OS after RT. The HPV- PSCC group had a higher frequency of TP53 mutations compared to HPV+ PSCC (75% vs 15%; p < 0.001). The results are limited by the retrospective nature of the data. CONCLUSIONS: Perioperative RT was more effective in the HPV+ PSCC subgroup. Reasons for the enhanced radiosensitivity may be related to the lack of TP53 mutations. PATIENT SUMMARY: We analyzed data from a large multicenter database for patients with penile cancer who had received inguinal lymph node dissection, with or without chemotherapy or radiotherapy. We found that for tumors positive for human papillomavirus (HPV), use of radiotherapy resulted in prolonged survival compared to HPV-negative tumors. On the basis of these results we are inspired to design studies on the use of radiotherapy in HPV-selected patients.